Journal: Int J Cardiol

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Abstract

LncRNA TUG1 silencing enhances proliferation and migration of ox-LDL-treated human umbilical vein endothelial cells and promotes atherosclerotic vascular injury repairing via the Runx2/ANPEP axis.

Du H, Yang L, Zhang H, Zhang X, Shao H
The role of vascular endothelial cell injury in the course of atherosclerosis (AS) has attracted increasing attention. Long non-coding RNAs (LncRNAs) are demonstrated to be the biomarker for the diagnosis of AS. This study investigated the mechanism of lncRNA taurine upregulated gene 1 (TUG1) in AS. Microarray data of AS obtained from GEO database showed that lncRNA TUG1 was differentially expressed in AS samples. TUG1 expression was upregulated in ox-LDL-treated human umbilical vein endothelial cells (HUVECs). Oxidized low density lipoprotein (ox-LDL)-treated HUVECs were then transfected with sh-TUG1. TUG1 silencing promoted proliferation and migration of ox-LDL-treated HUVECs. TUG1 bound to Runt-related transcription factor 2 (Runx2). Runx2 silencing promoted proliferation and migration of HUVECs. The downstream genes of Runx2 were predicted by hTFtarget database. The binding site of Runx2 and Aminopeptidase N (ANPEP) was determined. Runx2 silencing reversed the repression effect of overexpressing ANPEP on cell proliferation and migration. TUG1 silencing inhibited ANPEP expression via Runx2 to promote HUVEC proliferation and migration. A mouse model of AS was established. The area of atherosclerotic lesions of mouse aorta was detected, and vascular re-endothelialization was evaluated. TUG1 silencing promoted vascular injury repairing and inhibited AS in vivo. In conclusion, TUG1 silencing enhanced proliferation and migration of ox-LDL-treated HUVECs and promoted vascular injury repairing in vivo via the Runx2/ANPEP axis.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:204-214
Du H, Yang L, Zhang H, Zhang X, Shao H
Int J Cardiol: 31 Aug 2021; 338:204-214 | PMID: 33971184
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Abstract

National and regional registries for congenital heart diseases: Strengths, weaknesses and opportunities.

Chami J, Nicholson C, Strange G, Cordina R, Celermajer DS
Background
We aim to establish a new and informative bi-national Registry for Congenital Heart Disease (CHD) patients in Australia and New Zealand, to document the burden of disease and clinical outcomes for patients with CHDs across the lifespan. When planning for the implementation of this Registry, we sought to evaluate the strengths and weaknesses of existing national and large regional CHD databases.
Methods
We characterised 15 large multi-institutional databases of pediatric and/or adult patients with CHD, documenting the richness of their datasets, the ease of linkage to other databases, the coverage of the target cohort and the strategies utilised for quality control.
Results
The best databases contained demographic, clinical, physical, laboratory and patient-reported data, and were linked at least to the national/regional death registry. They also employed automatic data verification and regular manual audits. Coverage ranged from around 25% of all eligible CHD cases for larger databases to near 100% for some smaller registries of patients with specific CHD lesions, such as the Australia and New Zealand Fontan Registry.
Conclusions
Existing national and regional CHD databases have strengths and weaknesses; few combine complete coverage with high quality and regularly audited data, across the broad range of CHDs.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:89-94
Chami J, Nicholson C, Strange G, Cordina R, Celermajer DS
Int J Cardiol: 31 Aug 2021; 338:89-94 | PMID: 33965467
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Abstract

Cardiologist\'s approach to the diabetic patient: No further delay for a paradigm shift.

Maranta F, Cianfanelli L, Gaspardone C, Rizza V, ... Ambrosetti M, Cianflone D
Type 2 diabetes mellitus (DM) is constantly increasing worldwide and its most critical determinant of morbidity and mortality is still represented by cardiovascular (CV) complications. For years, cardiologists\' approach to diabetic patients has been focused on risk factors optimization, with positive results. However, the management of DM per se was never truly considered in order to obtain prevention from major CV events, because medications used for glycemic control were not expected to gain CV benefit. Early trials concerning intensive versus conventional glycemia control did not prove useful in reducing the number of CV events. The introduction of new molecules led to a game change in DM treatment, as some new glucose-lowering drugs (GLDs), such as sodium-glucose linked transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA), showed not only to be safe but also to ensure CV benefit. A combination of anti-atherogenic effects and hemodynamic improvements are likely explanations of the observed reduction of CV events and mortality. These evidence opened a completely new era in the field of GLDs and of DM treatment. Nonetheless, the presence of residual cardiovascular risk despite optimal medical therapy remains an issue and an aggressive strategy against multiple risk factors is suggested. A paradigm shift toward a new approach to DM management should be made with no further delay with the use of medications that may prevent CV events in an integrated strategy of CV risk reduction.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:248-257
Maranta F, Cianfanelli L, Gaspardone C, Rizza V, ... Ambrosetti M, Cianflone D
Int J Cardiol: 31 Aug 2021; 338:248-257 | PMID: 34058289
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Abstract

Sex-based differences in clinical outcomes and resource utilization of type 2 myocardial infarction.

Ariss RW, Elzanaty AM, Minhas AMK, Nazir S, ... Mochon A, Eltahawy EA
Background
Sex-based differences in clinical outcomes have been previously well described in type 1 myocardial infarction (T1MI). However, type 2 myocardial infarction (T2MI) is more common in contemporary practice, with scarce data regarding sex-based differences of outcomes.
Methods
The Nationwide Readmission Database 2018 was queried for hospitalizations with T2MI as a primary or secondary diagnosis. Complex samples multivariable logistic and linear regression models were used to determine the association between T2MI and outcomes (in-hospital mortality, index length of stay [LOS], hospital costs, discharge to nursing facility, and 30-day all-cause readmissions) in females compared to males with T2MI.
Results
A total of 252,641 hospitalizations [119,783 (47.4%) females and 132,858 (52.6%) males] were included in this analysis. Females with T2MI was associated with lower in-hospital mortality (adjusted odds ratio [aOR] 0.92; 95% confidence interval [CI] 0.88-0.96; P < 0.001), shorter LOS (adjusted parameter estimate [aPE] -0.28; 95% CI -0.38-0.17; P < 0.001), less hospital costs (aPE -1510.70; 95% CI -1916.04-1105.37; P < 0.001), and increased nursing home discharges (aOR 1.08; 95% CI 1.05-1.12; P < 0.001) compared to males with T2MI. Females and males with T2MI had similar rates of 30-day all-cause readmission (aOR 1.00; 95% CI 0.97-1.04; P = 0.841).
Conclusion
Among T2MI hospitalizations, females have lower in-hospital mortality, hospitalization costs, shorter LOS, and increased rates of nursing home discharge compared to males. Although statistically significant, the clinical significance of these small differences are unknown and require future studies.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:24-29
Ariss RW, Elzanaty AM, Minhas AMK, Nazir S, ... Mochon A, Eltahawy EA
Int J Cardiol: 31 Aug 2021; 338:24-29 | PMID: 34058288
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Abstract

Antithrombotic strategies in elderly patients with atrial fibrillation revascularized with drug-eluting stents: PACO-PCI (EPIC-15) registry.

de la Torre Hernandez JM, Ferreiro JL, Lopez-Palop R, Ojeda S, ... Garilleti C, Perez de Prado A
Background
We sought to investigate the antithrombotic regimens applied and their prognostic effects in patients over 75 years old with atrial fibrillation (AF) after revascularization with drug-eluting stents (DES).
Methods
Retrospective registry in 20 centers including patients over 75 years with AF treated with DES. A primary endpoint of MACCE and a co-primary endpoint of major bleeding by ISTH criteria were considered at 12 months.
Results
A total of 1249 patients (81.1 ± 4.2 years, 33.1% women, 66.6% ACS, 30.6% complex PCI) were included. Triple antithrombotic therapy (TAT) was prescribed in 81.7% and dual antithrombotic therapy (DAT) in 18.3%. TAT was based on direct oral anticoagulants (DOAC) in 48.4% and maintained for only 1 month in 52.2%, and DAT included DOAC in 70.6%. Primary endpoint of MACCE was met in 9.6% and primary endpoint of major bleeding in 9.4%. TAT was significantly associated with more bleeding (10.2% vs. 6.1%, p = 0.04) but less MACCE (8.7% vs. 13.6%, p = 0.02) than DAT and the use of DOAC was significantly associated to less bleeding (8% vs. 11.1%, p = 0.03) and similar MACCE (9.8% vs. 9.4%, p = 0.8). TAT over 1 month or with VKA was associated with more major bleeding but comparable MACCE rates.
Conclusions
Despite advanced age TAT prevails, but duration over 1 month or the use of other agent than Apixaban are associated with increased bleeding without additional MACCE prevention. DAT reduces bleeding but with a trade-off in terms of ischemic events. DOAC use was significantly associated to less bleeding and similar MACCE rates.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:63-71
de la Torre Hernandez JM, Ferreiro JL, Lopez-Palop R, Ojeda S, ... Garilleti C, Perez de Prado A
Int J Cardiol: 31 Aug 2021; 338:63-71 | PMID: 34062196
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Abstract

LncRNA PART1 alleviated myocardial ischemia/reperfusion injury via suppressing miR-503-5p/BIRC5 mediated mitochondrial apoptosis.

Guo Z, Zhao M, Jia G, Ma R, Li M
Background
Long non-coding RNA (lncRNA) is crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA PART1 on myocardial ischemia-reperfusion (I/R) injury by targeting BIRC5 through miR-503-5p pathway.
Methods
I/R model was created in vivo and vitro. The level of gene and protein was detected by RT-PCR and western blot. The apoptosis level was assessed by TUNEL and flow cytometry. Cell viability was determined by MTT. Mitochondrial function was evaluated by ATP content, ROS production, GSH level, and mitochondrial membrane potential. Cardiac function was confirmed by echocardiography, TTC staining, and H&E staining.
Results
Here, we found that the expression of lncRNA PART1 was down-regulated in the I/R hearts and H/R cardiomyocytes. Forced expression of PART1 remitted cardiac I/RI and H/R cardiomyocyte injury. Silencing of PART1 aggravated apoptosis and mitochondrial damage in cardiomyocytes. We found that PART1 functioned as a competing endogenous RNA of miR-503-5p, which decreased the expression of miR-503-5p. We further established BIRC5 as a target of miR-503-5p. Furthermore, PART1 prevented apoptosis and improved mitochondrial function in myocardial I/RI by targeting miR-503-5p/BIRC5.
Conclusions
In summary, PART1 protected mitochondrial function via miR-503-5p/BIRC5 pathway in MI/RI, which may provide the new theoretical basis for MI/RI treatment in the clinic.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 31 Aug 2021; 338:176-184
Guo Z, Zhao M, Jia G, Ma R, Li M
Int J Cardiol: 31 Aug 2021; 338:176-184 | PMID: 34082009
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Abstract

Insight into functional tricuspid valve regurgitation pathogenesis, pathological stages, and surgical management.

Sarraj-Asil A, Diez-Villanueva P
The tricuspid valve has generally been ignored, and considered as a \"second class structure\" in cardiac valve surgery. Tricuspid valve regurgitation is considered \"functional\" in over 70% of cases, generally produced by pulmonary hypertension secondary to left heart diseases in the context of an anatomically normal tricuspid valve apparatus. Many questions and doubts persist regarding to the pathogenesis of so-called functional tricuspid valve regurgitation. This article reviews the interfering factors in the function of the tricuspid valve to better identify the entity of the term \"functional\" and clarify its different pathological stages including the surgical procedures recommended in each stage.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:161-167
Sarraj-Asil A, Diez-Villanueva P
Int J Cardiol: 31 Aug 2021; 338:161-167 | PMID: 34087338
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Abstract

Cardiac glycosides are not associated with increased mortality or hospitalization rates in ICD and CRT-ICD patients after adjustment for baseline-characteristics at one-year follow-up: Results from the German DEVICE registry.

Bode N, Hochadel M, Andresen D, Zahn R, ... Senges J, Eckardt L
Aims
Despite lacking supporting randomized trials, cardiac glycosides (CGs) are widely used in heart failure and/or atrial fibrillation. Moreover, several pro- and retrospective studies and registry-data have recently raised serious concerns in terms of efficacy and safety of CGs in this field. We have therefore examined the association between CGs and clinical outcome of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization (CRT-ICD) patients of the large German DEVICE registry.
Methods and results
Between 2007 and 2014, 3782 ICD and 1529 CRT-ICD patients were enrolled in the German DEVICE registry. Those two groups were analyzed independently according to medication with or without CGs. After adjustment for patient characteristics, CGs were not significantly associated with increased one-year mortality (HR 1.27, 95%-CI 0.91-1.76, p = 0.162), major adverse cardiac and cerebrovascular events (OR 1.36, 95%-CI 0.98-1.89, p = 0.063), ICD-shocks (OR 1.29, 95%-CI 0.95-1.74, p = 0.104) or the need for rehospitalization in ICD patients at one-year-follow-up. Similar findings were obtained in CRT-ICD patients. Regarding possible determinants for glycoside treatment, atrial fibrillation at enrollment was found to be most strongly associated with the prescription of glycosides in ICD (adjusted OR 3.25, 95%-CI 2.63-4.02) and CRT-ICD patients (adjusted OR 3.17, 95%-CI 2.39-4.19).
Conclusion
Overall harmful effects of CGs in ICD- and CRT-ICD patients could not be confirmed in DEVICE. Further large and randomized-controlled trials that investigate dose-dependent effects of CGs in addition to contemporary therapy of heart failure and atrial fibrillation are needed.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 31 Aug 2021; 338:109-114
Bode N, Hochadel M, Andresen D, Zahn R, ... Senges J, Eckardt L
Int J Cardiol: 31 Aug 2021; 338:109-114 | PMID: 34087337
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Abstract

Associations of time-varying obesity and metabolic syndrome with risk of incident heart failure and its subtypes: Findings from the Multi-Ethnic Study of Atherosclerosis.

Liu L, Lima JAC, Post WS, Szklo M
Objective
Most previous studies have examined associations between metabolic disorders measured at a single point in time and risk of heart failure (HF). However, there are many situations where the values of exposures vary over time before HF occurs. We aimed to examine the associations of time-varying obesity and metabolic syndrome (MetSyn) measured at multiple points in time with HF.
Methods
A total of 6750 participants in the Multi-Ethnic Study of Atherosclerosis from 2000 were included in the study. Follow-up was completed through December 2015. MetSyn was defined using the American Heart Association criteria. Incident HF was diagnosed by clinical criteria. Subtypes HF (reduced ejection fraction (HFrEF) and preserved (HFpEF) were classified by left ventricular EF.
Results
A total of 331 HF cases were identified during 82,609 person-years of observation. The incidence (95%CI) of total HF was 4.0 (3.4-4.4) per 1000 person-years. Of the total HF cases, 45.6% were HFrEF (n = 151), 40.8% HFpEF (n = 135), and 13.6% were unclassified HF subtypes (n = 45). After adjusting for key covariates, time-varying obesity (BMI ≥ 30 kg/m2) and MetSyn were significantly associated with HF, with a stronger association for HFpEF than for HFrEF. The corresponding hazards ratios (HR, 95%CI) were 1.97 (1.43-2.72) and 1.86 (1.43-2.42) for HFpEF, and 1.46 (1.07-1.98), and 1.39 (1.06-1.82) for HFrEF respectively. Time-varying large waist circumference was significantly associated with for HFpEF, but not with HFrEF.
Conclusion
Time-varying obesity and MetSyn were significantly associated with HF risk, with a stronger association with HFpEF than with HFrEF. Continued effort to control these risk factors is recommended.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:127-135
Liu L, Lima JAC, Post WS, Szklo M
Int J Cardiol: 31 Aug 2021; 338:127-135 | PMID: 34089770
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Abstract

LncRNA KCNQ1OT1 as a miR-26a-5p sponge regulates ATG12-mediated cardiomyocyte autophagy and aggravates myocardial infarction.

Li J, Tong Y, Zhou Y, Han Z, ... Zhang X, Qiu C
Background
As a dominant cardiovascular disease, myocardial infarction (MI) causes a considerable mortality globally. KCNQ1 overlapping transcript 1 (KCNQ1OT1) was reported to be overexpressed in MI patients. However, the detailed mechanisms remain unclear.
Methods
We analyzed the expression of KCNQ1OT1 in the serum of MI patients, and built ischemia/reperfusion (I/R) mouse and H/R-induced cell model. TTC staining was used to evaluate infarct size in mice. TUNEL was employed to assess cell apoptosis. QRT-PCR was performed to detect the expression of KCNQ1OT1 and miR-26a-5p. The formation of autophagosomes in cells was detected by immunofluorescence. Caspase3 activity was detected by the Caspase-3 Assay Kit. Autophagy and apoptosis-related proteins were assessed by western blotting. Luciferase reporter assay was used to assess the binding relationship of KCNQ1OT1 and miR-26a-5p and miR-20a-5p/ATG12.
Results
KCNQ1OT1 was up-regulated while miR-26a-5p was decreased in MI patients, I/R mouse and H/R-induced cell model. KCNQ1OT1 knockdown inhibited cell autophagy and protected cardiomyocytes from apoptosis by up-regulating miR-26a-5p. Either KCNQ1OT1 knockdown or miR-26a-5p mimics caused inhibition of autophagy related 12 homolog (ATG12), which was the direct target of miR-26a-5p. In vivo, KCNQ1OT1 promoted cardiomyocytes apoptosis via miR-26a-5p/ATG12 pathway.
Conclusion
KCNQ1OT1/miR-26a-5p/ATG12 axis regulated cardiomyocyte autophagy and apoptosis, both in vivo and in vitro. These data supported that KCNQ1OT1 inhibition might be a promising therapeutic option for protection after MI.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 31 Aug 2021; 338:14-23
Li J, Tong Y, Zhou Y, Han Z, ... Zhang X, Qiu C
Int J Cardiol: 31 Aug 2021; 338:14-23 | PMID: 34089766
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Abstract

Cost-utility analysis of heart surgeries for young adults with severe rheumatic mitral valve disease in India.

Uy J, Ketkar AG, Portnoy A, Kim JJ
Background
Rheumatic mitral valve disease (RMVD) is a major cause of acquired valvular disease in India. We compared the cost-effectiveness of surgical treatment strategies for young adults with severe RMVD from an Indian public payer perspective.
Methods
We developed a Markov model to reflect the burden of RMVD among a hypothetical cohort of 20-year-olds in India and to estimate quality-adjusted life years (QALYs) and lifetime costs associated with three strategies: (1) Repair; (2) Mechanical valve replacement (MVR-M); and (3) Bioprosthetic valve replacement (MVR-B), compared to a baseline strategy involving a mix of surgeries approximating the standard of care in India (32% Repair, 33% MVR-M, 35% MVR-B). Data on disease burden, intervention effects, and direct medical costs (2018 US$) were obtained from the literature. Deterministic and probabilistic sensitivity analyses were conducted to assess model uncertainty.
Results
Repair ($2530, 9.7 QALYs) was less costly and more effective than the standard of care ($2990, 8.7 QALYs) and MVR-M ($3220, 6.2 QALYs). The incremental cost-effective ratio for MVR-B ($3190, 10.1 QALYs) compared to Repair was $1590 per QALY, which may be cost-effective at a threshold of India\'s per-capita gross domestic product (GDP: $2005). The optimal choice between Repair or MVR-B was sensitive to variations in surgery costs, background mortality, and risks for reoperation.
Conclusions
Our model-based analysis suggests that Repair is the optimal strategy and MVR-M should not be recommended for this subpopulation. MVR-B may be cost-effective in contexts where quality of Repair is not assured, newer generation bioprostheses are used, or the costs of the bioprosthetic valve decrease.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:50-57
Uy J, Ketkar AG, Portnoy A, Kim JJ
Int J Cardiol: 31 Aug 2021; 338:50-57 | PMID: 34090957
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Abstract

Aortic angle distribution and predictors of horizontal aorta in patients undergoing transcatheter aortic valve replacement.

Moscarelli M, Gallo F, Gallone G, Kim WK, ... Colombo A, Giannini F
Background
Horizontal aorta (HA) is an anatomical feature that can pose significant technical challenges for the successful positioning of the bioprosthetic valve during transcatheter aortic valve replacement (TAVR). Physiological range of aortic angle (AA) is unknown; hence there is no cutoff AA for classifying HA. Moreover, patient characteristics predicting HA are under-investigated.
Methods
This was a retrospective analysis of prospective collected data from 16 heart valve centers in Europe. The study utilized a common dataset with a priori agreed-upon definitions and variables. Eligible patients underwent TAVR between 2014 and 2020 and had multidetector computed tomographic imaging data available for determining the AA. The analysis described the distribution of AA and potential predictors of HA. Inter-center variability was also explored.
Results
For 4022 patients analyzed, the mean AA ± standard deviation was 49.4° ± 9.4° (median 49°, inter-quartile range [IQR] 12°, range 18-90°). There was no significant difference in mean AA between men and women (49.4° ± 9.1° vs. 49.6° ± 9.3°, respectively; p = 0.53); therefore, 49.4° was accepted as the cutoff value for HA in subsequent analyses. Covariates significantly associated with HA included age (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.04, p < 0.001), body mass index (OR: 1.06, 95% CI: 1.05-1.08, p < 0.01), previous cardiac surgery (OR: 0.58, 95% CI: 0.45-0.75, p < 0.001), and porcelain aorta (OR: 0.66, 95% CI: 0.52-0.85, p = 0.001). Some inter-center variability was observed.
Conclusions
We defined 49.4° as the mean AA, and also associated predictors of HA in a large case series of patients with severe aortic stenosis candidates for TAVR.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:58-62
Moscarelli M, Gallo F, Gallone G, Kim WK, ... Colombo A, Giannini F
Int J Cardiol: 31 Aug 2021; 338:58-62 | PMID: 34090956
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Abstract

Metagenomic analysis of gut microbiota reveals its role in trimethylamine metabolism in heart failure.

Emoto T, Hayashi T, Tabata T, Yamashita T, ... Yamada T, Hirata KI
Background
We had previously reported an increase in trimethylamine N-oxide (TMAO) levels in patients with both compensated and decompensated heart failure (HF) and alteration in gut microbiota composition using 16S rRNA gene amplicon analysis. Although a metagenome-wide analysis showed that choline-TMA lyase levels increased in HF patients, which TMA generation pathway from choline, carnitine, or betaine contributes to the increase in TMAO levels in HF needs to be elucidated.
Methods
We conducted a metagenome-wide shotgun sequencing analysis of gut microbiota and measured the TMAO levels in plasma of 22 HF patients during the compensated phase and 11 age-, sex-, and comorbidity-matched control subjects, whose gut microbiota compositions were reported in a previous 16S rRNA-based analysis.
Results
The abundance of cntA/B was positively correlated with TMAO, especially in HF patients, whereas that of cutC/D or betaine reductase was not correlated either in controls or HF patients. The abundance of cntA/B was mainly derived from the genera Escherichia and Klebsiella either in controls or HF patients.
Conclusion
TMAO levels in plasma depend on the abundance of cntA/B in HF. Although it is difficult to exclude the involvement of confounding factors, microbial dysbiosis connecting the abundance of cntA/B in the gut and the increase of TMAO in plasma can be a therapeutic target for HF.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:138-142
Emoto T, Hayashi T, Tabata T, Yamashita T, ... Yamada T, Hirata KI
Int J Cardiol: 31 Aug 2021; 338:138-142 | PMID: 34102245
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Abstract

Functional heart recovery in an adult mammal, the spiny mouse.

Qi Y, Dasa O, Maden M, Vohra R, ... Raizada MK, Pepine CJ
Background
Ischemic heart disease and the resulting heart failure continue to carry high morbidity and mortality, and a breakthrough in our understanding of this disorder is needed. The adult spiny mouse (Acomys cahirinus) has evolved the remarkable capacity to regenerate full-thickness skin tissue, including microvasculature and cartilage, without fibrosis or scarring. We hypothesized that lack of scarring and resulting functional regeneration also applies to the adult Acomys heart.
Methods and results
We compared responses of the Acomys heart to CD1 outbred Mus heart following acute left anterior descending coronary artery ligation to induce myocardial infarction. Both Acomys and Mus hearts showed decreased ejection fraction (EF) after ligation. However, Acomys hearts showed significant EF recovery to pre-ligation values over four weeks. Histological analysis showed comparable infarct area 24-h after ligation with a similar collateral flow in both species\' hearts, but subsequently, Acomys displayed reduced infarct size, regenerated microvasculature, and increased cell proliferative activity in the infarcted area.
Conclusions
These observations suggest that adult Acomys displays remarkable cardiac recovery properties after acute coronary artery occlusion and may be a useful model to understand functional recovery better.
Translational perspective
Adult Acomys provides a novel mammalian model to further investigate the cardioprotective and regenerative signaling mechanisms in adult mammals. This opens the door to breakthrough treatment strategies for the injured myocardium and help millions of patients with heart failure secondary to tissue injury with irreversible damage.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:196-203
Qi Y, Dasa O, Maden M, Vohra R, ... Raizada MK, Pepine CJ
Int J Cardiol: 31 Aug 2021; 338:196-203 | PMID: 34126132
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Abstract

Impact of myocardial injury and inflammation due to ablation on the short-term and mid-term outcomes: Cryoballoon versus laser balloon ablation.

Yano M, Egami Y, Ukita K, Kawamura A, ... Nishino M, Tanouchi J
Background
Cryoballoon ablation (CBA) and laser balloon ablation (LBA) were developed as alternatives to conventional radiofrequency ablation for paroxysmal atrial fibrillation (PAF). Pathological findings after ablation such as myocardial injury and inflammation are thought to be different between CBA and LBA. However, the different impact of myocardial injury and inflammation after ablation on short- and mid-term outcomes remains unclear.
Methods
Consecutive PAF patients who underwent CBA and LBA were enrolled from the Osaka Rosai Atrial Fibrillation ablation (ORAF) registry. The difference of the acute myocardial injury marker (hs-TnI), and changes of inflammation markers (C reactive protein; ΔCRP, and white blood cell; ΔWBC) after catheter ablation and the difference of the short-term (within 3 months after ablation) and mid-term (from 3 months to 6 months after ablation) outcomes were evaluated between the two groups.
Results
The CBA and LBA groups consisted of 55 and 56 patients, respectively. After propensity score matching, CBA and LBA groups consisted of 37 patients, respectively. Hs-TnI value was significantly higher in CBA than LBA group, while ΔCRP and ΔWBC were significantly higher in LBA than CBA group. In the propensity score-matched pairs, the LBA group had a significantly greater risk of short-term arrhythmia recurrence than the CBA group, whereas no significant difference of mid-term arrhythmia recurrence were found between the two groups.
Conclusion
Myocardial injury and inflammation status differ between CBA and LBA groups. LBA group had stronger inflammation after ablation and had a significantly greater risk of short-term arrhythmia recurrence after PVI than CBA group.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:102-108
Yano M, Egami Y, Ukita K, Kawamura A, ... Nishino M, Tanouchi J
Int J Cardiol: 31 Aug 2021; 338:102-108 | PMID: 34126131
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Abstract

Efficacy and safety of ticagrelor versus prasugrel in smokers and nonsmokers with acute coronary syndromes.

Lahu S, Ndrepepa G, Gewalt S, Schüpke S, ... Kastrati A, Mayer K
Background
The efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with acute coronary syndromes (ACS) are not known. We assessed the efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with ACS undergoing invasive management.
Methods
This pre-specified analysis of the ISAR-REACT 5 trial included 1349 smokers and 2652 nonsmokers randomized to receive ticagrelor or prasugrel. The primary endpoint was the incidence of death, myocardial infarction, or stroke; the secondary endpoint was the incidence of Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding (both endpoints assessed at 12 months).
Results
There was no significant treatment arm-by-smoking status interaction regarding the efficacy outcome. The primary endpoint occurred in 47 patients (7.0%) in the ticagrelor group and 41 patients (6.2%) in the prasugrel group in smokers (hazard ratio [HR] = 1.15; 95% confidence interval [CI] 0.76-1.75; P = 0.510) and in 133 patients (10.2%) in the ticagrelor group and 94 patients (7.2%) in the prasugrel group in nonsmokers (HR = 1.44 [1.10-1.87]; P = 0.007; P for interaction = 0.378). The secondary endpoint occurred in 27 patients (4.6%) in the ticagrelor group and 33 patients (5.6%) in the prasugrel group in smokers (HR = 0.81 [0.49-1.35]; P = 0.412) and in 66 patients (6.0%) in the ticagrelor group and 46 patients (4.4%) in the prasugrel group in nonsmokers (HR = 1.38 [0.94-2.01]; P = 0.097).
Conclusions
In patients with ACS undergoing an invasive management strategy, the smoking status did not significantly interact with the relative treatment effect of ticagrelor vs. prasugrel.
Clinical trial registration
NCT01944800.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:8-13
Lahu S, Ndrepepa G, Gewalt S, Schüpke S, ... Kastrati A, Mayer K
Int J Cardiol: 31 Aug 2021; 338:8-13 | PMID: 34126130
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Impact:
Abstract

Noninvasive assessment of congestive hepatopathy in patients with constrictive pericardial physiology using MR relaxometry.

Bogaert J, Dresselaers T, Imazio M, Sinnaeve P, ... Masci PG, Symons R
Background
Constrictive pericarditis represents a treatable cause of mainly right heart failure (RHF), characterized by increased filling pressures and congestive hepatopathy. We hypothesized assessment of T1 and T2 liver relaxation times enables to depict liver congestion, and thus to diagnose RHF.
Methods
Cardiovascular magnetic resonance imaging (CMR) was performed in 45 pericarditis patients i.e., 25 with constrictive physiology (CP+), 20 with normal physiology (CP-), and 30 control subjects. CMR included morphologic and functional assessment of the heart and pericardium. Liver relaxation times were measured on T1 and T2 cardiac maps.
Results
CP+ and CP- patients were predominantly male, but CP+ patients were on average 13 years older than CP- patients (p = 0.003). T1 and T2 Liver values were significantly higher in CP+ than in CP- patients and controls, i.e. T1: 765 ± 102 ms vs 581 ± 56 ms and 537 ± 30 ms (both p < 0.001); T2: 63 ± 13 ms vs 50 ± 4 ms and 46 ± 4 ms (both p < 0.001). Extracellular volume (ECV) liver values were also increased, i.e. 42 ± 7% CP+ vs 31 ± 3% CP- and 30 ± 3% control (both p < 0.001). Using a cut-off right atrial pressure of >5 mmHg to discriminate between normal and increased pressure, native T1 liver yielded the highest AUC (0.926) at ROC analysis with a sensitivity of 79.3% and specificity of 95.6%. Gamma-glutamyl transpeptidase correlated well withT1 liver (r2 = 0.43) and ECV liver (r2 = 0.30). Excellent intra- and inter-reader agreement was found for T1, T2 and ECV measurement of the liver.
Conclusions
Assessment of liver relaxation times in pericarditis patients provide valuable information on the presence of concomitant congestive hepatopathy, reflecting RHF.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:265-273
Bogaert J, Dresselaers T, Imazio M, Sinnaeve P, ... Masci PG, Symons R
Int J Cardiol: 31 Aug 2021; 338:265-273 | PMID: 34153414
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Impact:
Abstract

Safety and long-term outcomes of catheter ablation according to sex in patients with atrial fibrillation: A nationwide cohort study.

Kim MH, You SC, Sung JH, Jang E, ... Yang PS, Joung B
Background
Catheter ablation is more effective than antiarrhythmic drug therapy alone in patients with atrial fibrillation (AF). However, there are limited data on the outcomes of AF ablation according to sex. The purpose of this study was to evaluate gender differences in the actual outcomes after catheter ablation for atrial fibrillation.
Methods
Of 801,710 patients with AF in the Korean National Health Insurance Service database, we identified 9175 patients without valvular heart disease who underwent AF ablation between 2006 and 2015 and assessed 30-day safety and one-year effectiveness outcomes according to sex.
Results
Of the 9175 patients who underwent AF ablation, 2206 (24%) were female. Women, compared to men, were older (60.8 ± 10.2 vs. 56.0 ± 10.5 years), had higher CHA2DS2-VASc (3.5 ± 1.7 vs. 2.0 ± 1.6), higher HAS-BLED (2.6 ± 1.3 vs. 2.4 ± 1.2), and higher Charlson comorbidity index scores (3.8 ± 2.6 vs. 3.1 ± 2.5) (p < 0.001 for all). Following ablation, there was no significant difference in the risk of 30-day complications, including hemorrhage and tamponade, between women and men. In multivariable analyses, there were no significant differences in all-cause hospitalization (adjusted hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.91-1.22, p = 0.489) and AF rehospitalization (adjusted HR 1.16, 95% CI 0.96-1.40, p = 0.135). Women were less likely to undergo cardioversion (adjusted HR 0.72, 95% CI 0.62-0.84, p < 0.001) but were more likely to be re-hospitalized for heart failure (adjusted HR 1.86, 95% CI 1.11-3.11, p = 0.019).
Conclusion
Women who underwent AF ablation did not differ from men in terms of the risk of complications and all-cause hospitalization in this study. The small increased risk in women reported in previous studies may be related to residual confounding, particularly from insufficient control for age and comorbidities.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:95-101
Kim MH, You SC, Sung JH, Jang E, ... Yang PS, Joung B
Int J Cardiol: 31 Aug 2021; 338:95-101 | PMID: 34147556
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Impact:
Abstract

Operator preference and determinants of size selection when additional intermediate-size aortic transcatheter heart valves are made available.

Kawashima H, Serruys PW, Mylotte D, Rosseel L, ... Baumbach A, Soliman O
Background
Appropriate size selection of transcatheter heart valves (THVs) is fundamental to reduce transcatheter aortic valve implantation (TAVI) related complications, particularly paravalvular aortic regurgitation, new permanent pacemaker implantation, and annular rupture. We sought to investigate the frequency of operator selection of intermediate-size balloon-expandable Myval THVs (Meril Life Sciences Pvt. Ltd., India) for TAVI in a real-world dataset.
Methods
In this retrospective survey of patients treated with TAVI using the Myval THV, 20, 23, 26, and 29 mm are conventional-size THVs, 21.5, 24.5 and 27.5 mm are intermediate-size THVs, and 30.5 and 32 mm are extra-large THVs. Operator size selection for implantation was based on multislice computed tomography (MSCT) derived aortic-root dimensions.
Results
A total of 1115 patients underwent Myval THV implantation in 27 countries worldwide. The Myval intermediate-size THVs were used in 468 (42.0%) patients. MSCT data were available in 562 patients. There was no statistical difference between the Intermediate/Upsized and Appropriately sized groups or Intermediate/Downsized and Appropriately sized groups in terms of different variables measured with MSCT except for annular dimensions and degree of calcification.
Conclusions
Intermediate-size Myval balloon-expandable THVs are used in nearly half of all cases in contemporary real-world TAVI practice, addressing the unmet need of TAVI operators for a more calibrated THV choice. Our hypothesis should be tested in randomized prospective studies currently initiated in Europe, including clinical outcomes of patients treated with both conventional- and intermediate-size THVs.

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:168-173
Kawashima H, Serruys PW, Mylotte D, Rosseel L, ... Baumbach A, Soliman O
Int J Cardiol: 31 Aug 2021; 338:168-173 | PMID: 34147554
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Impact:
Abstract

C-reactive protein velocity predicts microvascular pathology after acute ST-elevation myocardial infarction.

Holzknecht M, Tiller C, Reindl M, Lechner I, ... Metzler B, Reinstadler SJ
Background
The role of C-reactive protein velocity (CRPv) as an early and sensitive marker of an excessive inflammatory response in the setting of acute ST-elevation myocardial infarction (STEMI) is only poorly understood. The aim of this study was to investigate, in patients with STEMI treated with primary percutaneous coronary intervention (PCI), the association of CRPv with microvascular infarct pathology.
Methods and results
This prospective cohort study included a total of 316 patients with STEMI undergoing PCI. CRPv was defined as the difference between CRP 24 ± 8 h and CRP at hospital admission, divided by the time (in h) that have passed during the two examinations. The association of biomarker levels with cardiac magnetic resonance (CMR)-determined microvascular obstruction (MVO) was evaluated. CMR was performed at a median of 3 [interquartile range 2-4] days after PCI. After adjustment for cardiac troponin T (cTnT), anterior infarction and TIMI flow pre and post-PCI, CRPv (odds ratio 2.70, 95% confidence interval (CI) 1.54-4.73; p = 0.001) remained significantly associated with the occurrence of MVO. CRPv (area under the curve [AUC] 0.76, 95% CI 0.71-0.81; p < 0.001) was a better predictor for MVO compared to 24 h CRP (AUC difference: 0.03, p = 0.002). The addition of CRPv to peak cTnT resulted in a higher AUC for MVO prediction than peak cTnT alone (AUC 0.86, 95% CI 0.82-0.90; p < 0.001 vs. AUC 0.84, 95% CI 0.79-0.88; p < 0.001. AUC difference: 0.02, p = 0.042).
Conclusions
In patients with STEMI treated with primary PCI, CRPv was associated with microvascular infarct pathology with a predictive value incremental to cTnT, suggesting CRPv as an early and sensitive biomarker for more severe infarct pathology and outcome.

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:30-36
Holzknecht M, Tiller C, Reindl M, Lechner I, ... Metzler B, Reinstadler SJ
Int J Cardiol: 31 Aug 2021; 338:30-36 | PMID: 34147553
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Impact:
Abstract

Pediatric rheumatic carditis in Italy and Rwanda: The same disease, different socio-economic settings.

Fabi M, Calicchia M, Palleri D, Ndikubwimana I, ... Gargiulo G, Lanari M
Background
Acute Rheumatic Fever and Rheumatic Heart Disease are the leading cause of acquired heart disease in Low-Income Countries, and a common cause in High-Income Countries. We compared rheumatic carditis, its echocardiographic presentation at diagnosis and its progression in Italy and Rwanda.
Methods
Retrospective study including all consecutive patients diagnosed with rheumatic carditis in an Italian (IT) and two Rwandan Hospitals (RW). Echocardiography was performed at diagnosis and three follow-up visits. Baseline characteristics, history of primary and secondary prophylaxis and cardiovascular complications data were collected.
Results
Seventy-nine and 135 patients were enrolled in IT and RW, respectively. Mitral regurgitation was the most common lesion (IT: 70%, RW: 96%) in both cohorts; mixed valve lesions and severe lesions were more prevalent in RW. Age at diagnosis (IT: 8.4 ± 2.9 yrs.; RW: 11.1 ± 2.7 yrs.; P < 0.001), adherence to secondary prophylaxis (IT: 99%; RW: 48%; P < 0.001) and history of primary prophylaxis (IT: 65%; RW: 6%; P < 0.001) were different. During the follow-up, native valve lesions completely resolved in 38% of IT and in 2% of RW patients (P < 0.001). By contrast, cardiac surgery was performed in 31% of RW and 5% of IT patients (P < 0.001). Cardiovascular complications and death were only observed in RW.
Conclusions
The more severe cardiac involvement, the higher rate of valve surgery, CV complications and deaths in RW, could be due to delayed diagnosis and treatment, scarce adherence to secondary prophylaxis and differences in social determinants of health.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:154-160
Fabi M, Calicchia M, Palleri D, Ndikubwimana I, ... Gargiulo G, Lanari M
Int J Cardiol: 31 Aug 2021; 338:154-160 | PMID: 34146584
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Impact:
Abstract

Extensive and balanced reduction of myocardial blood flow in patients with suspected obstructive coronary artery disease: 15O-water PET study.

Maaniitty T, Stenström I, Saraste A, Knuuti J
Background
Detection of obstructive coronary artery disease (CAD) by stress myocardial perfusion imaging (MPI) is conventionally based on relative differences in perfusion. This may lead to either underestimation of the extent of myocardial ischemia, or the ischemia might be completely missed in case of balanced perfusion reduction. Using absolute quantification of myocardial blood flow (MBF) by positron emission tomography (PET), we evaluated how common are extensive and balanced myocardial perfusion abnormalities in symptomatic patients with suspected obstructive CAD.
Methods and results
Among 758 consecutive symptomatic patients undergone coronary computed tomography angiography (CTA), 286 patients subsequently underwent quantitative 15O-water adenosine-stress PET MPI to assess the hemodynamic significance of suspected obstructive stenosis. Out of these, 46 (16%) patients had reduced (≤2.3 ml/g/min) absolute stress MBF in all three standard coronary territories (LAD, LCX, RCA). Subsequently, relative stress MBF in each coronary territory was calculated, considering a territory with the highest absolute stress MBF as a reference region. Among the 46 patients, 72% had significant regional heterogeneity in myocardial perfusion (defined as having ≥1 territory with relative stress MBF <80%) while the remaining 28% (4.5% of the whole MPI cohort) showed balanced perfusion reduction (all relative MBF values ≥80%).
Conclusions
Among symptomatic patients with suspected obstructive stenosis on coronary CTA, quantitative PET revealed that 16% of patients had reduced stress MBF involving all three coronary artery territories, of whom approximately one third showed balanced reduction. Thus, in 4.5% of the patients the perfusion abnormalities could have been missed by conventional relative MPI analysis.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:1-7
Maaniitty T, Stenström I, Saraste A, Knuuti J
Int J Cardiol: 31 Aug 2021; 338:1-7 | PMID: 34144073
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Impact:
Abstract

Granzyme K - A novel marker to identify the presence and rupture of abdominal aortic aneurysm.

Li T, Yang C, Jing J, Sun L, Yuan Y
Background
Immune inflammatory dysfunction is a hallmark of abdominal aortic aneurysm (AAA). Granzyme K (GZMK) is involved in the regulation of inflammation. However, the correlation between GZMK expression and AAA risk remains unknown.
Methods
This case-control study included 112 AAA patients and 112 controls. Serum GZMK levels were determined by enzyme-linked immunosorbent assay and immunohistochemistry was utilized to determine GZMK expression in aortic tissues.
Results
Compared with controls, AAA patients had higher levels of serum GZMK, and GZMK expression in AAA tissues was increased and positively associated with its serum levels (r = 0.688, P = 0.019). A positive association of serum GZMK levels with CRP or AAA diameter was confirmed, while there was a relationship between tissue GZMK expression and AAA diameter. The AUC of serum GZMK for AAA diagnosis was 0.78 with the sensitivity and specificity of 62.5% and 81.2%, whereas AUC for rupture detection was 0.76 with a sensitivity of 90.0% and specificity of 51.3%. A combination of clinically used inflammatory parameters with serum GZMK could enhance the accuracy of WBC or CRP alone in detecting AAA or rupture type. Multiple logistic analyses revealed an association of per unit increase of serum GZMK with AAA presence (OR = 1.046, P < 0.001) and its rupture risk (OR = 1.015, P = 0.048) after adjusting for confounding factors.
Conclusions
Our study provides proof that elevated GZMK expression both in serum and tissues is correlated with the presence of AAA, and serum GZMK may be a useful non-invasive marker that helps to identify AAA and its rupture risk in clinical practice.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:242-247
Li T, Yang C, Jing J, Sun L, Yuan Y
Int J Cardiol: 31 Aug 2021; 338:242-247 | PMID: 34139229
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Impact:
Abstract

Rapid prediction of deterioration risk among non-high-risk patients with acute pulmonary embolism at admission: An imaging tool.

Gao Y, Wang Y, Cao X, Wang X, ... Zhao H, Jia D
Background
Computed tomography (CT) pulmonary angiography as the first-line diagnosis tool of acute pulmonary embolism (PE), might improve this discriminatory power. We aimed to developed a simply tool combining multi-CT parameters to complete individualized risk assessment of deterioration in non-high-risk patients with acute PE at admission.
Method
Consecutive non-high-risk patients with acute PE who were treated in a Chinese center during 2010-2021, were collected.Prognosis-related CT parameters were reviewed. Deterioration was defined as any adverse event within 30 day after admission. Eligible patients were randomized into derivation and validation cohorts. In the derivation cohort, CT parameters were screened for importance using classification tree methodology and enrolled variables was partitioned via curve-fitting and dose-response analysis. A nomogram was developed and the predictive power in both cohorts was evaluated based on the area under the receiver operating characteristic curve (AUROC) and the corresponding 95% confidence interval (CI).
Result
A total of 1001 patients were included. The preliminary analyses revealed that deterioration risk was related to the right-to-left ventricular diameter ratio at 4-chamber view, pulmonary vein filling abnormality. After a curve-fitting to deterioration risk, these parameters were partitioned and used to develop a nomogram, which had AUROC values of 0.91 (95% CI: 0.87-0.96) in the derivation cohort and 0.89 (95% CI: 0.81-0.97) in the validation cohort. A web-based version of the radiomics scoring tool was published online for use in clinical practice (https://acutepeprediction.shinyapps.io/Radiomics_Predictive_Tool/).
Conclusion
This simply tool can complete rapid estimation of deterioration risk among non-high-risk acute PE patients at admission.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:229-236
Gao Y, Wang Y, Cao X, Wang X, ... Zhao H, Jia D
Int J Cardiol: 31 Aug 2021; 338:229-236 | PMID: 34139228
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Impact:
Abstract

HS alleviates aortic aneurysm and dissection: Crosstalk between transforming growth factor 1 signaling and NLRP3 inflammasome.

Cui J, Xu G, Bian F
Background
Vascular remodeling and inflammation are involved in aortic aneurysm (AA) and aortic dissection (AD). TGF-β1 signaling is involved in tissue fibrosis, extracellular matrix remodeling and inflammation, which are linked with AA and AD. The inhibition of NLRP3 inflammasome suppresses AA and AD. Hydrogen sulfide (H2S) exerts anti-vascular remodeling and anti-inflammatory properties, but little is known about its action on AA and AD progression.
Methods
The effect of H2S on AA and AD formation was investigated in Sprague-Dawley (SD) rat fed a normal diet supplemented with 0.25% β-aminopropionitrile (BAPN). HE staining, Masson\'s trichrome staining, Picrosirius red staining and EVG staining were to evaluate vascular remodeling in the aortic wall. Western blotting and IHC were to detect the expression of TGF-β1 and matrix metalloproteinases (MMPs) and NLRP3 inflammasome-associated proteins. The interaction between TGF-β1 signaling and NLRP3 inflammasome was explored in Human aortic vascular smooth muscle cells (HA-VSMCs).
Results
H2S alleviated AA and AD progression. Specifically, it improved irregular tissue arrangement and vascular fibrosis, increased the expression of elastin fibers, decreased collagen deposition and the expression of TGF-β1 and matrix metalloproteinases (MMP-2/9). In addition, H2S inhibited the expression of proteins involved in NLRP3 inflammasome. Furthermore, H2S down-regulated TGF-β1 signaling and then ameliorated vascular fibrosis by preventing NLRP3 inflammasome activation. Finally, H2S inhibited NLRP3 inflammasome activation and decreased the level of IL-1β by disrupting TGF-β1 signaling.
Conclusions
These data support a crosstalk between TGF-β1 signaling and NLRP3 inflammasome. H2S inhibits AA and AD progression via blocking the crosstalk.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 31 Aug 2021; 338:215-225
Cui J, Xu G, Bian F
Int J Cardiol: 31 Aug 2021; 338:215-225 | PMID: 34157359
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Impact:
Abstract

Prevalence and characteristics of myocardial injury during COVID-19 pandemic: A new role for high-sensitive troponin.

Maino A, Di Stasio E, Grimaldi MC, Cappannoli L, ... Landolfi R, Biasucci LM
Background
Coronavirus disease 2019 (COVID-19) is a pandemic disease that is causing a public health emergency. Characteristics and clinical significance of myocardial injury remain unclear.
Methods
This retrospective single-center study analyzed 189 patients who received a COVID-19 diagnosis out of all 758 subjects with a high sensitive troponin I (Hs-TnI) measurement within the first 24 h of admission at the Policlinico A.Gemelli (Rome, Italy) between February 20th 2020 to April 09th 2020.
Results
The prevalence of myocardial injury in our COVID-19 population is of 16%. The patients with cardiac injury were older, had a greater number of cardiovascular comorbidities and higher values of acute phase and inflammatory markers and leucocytes. They required more frequently hospitalization in Intensive Care Unit (10 [32.3%] vs 18 [11.4%]; p = .003) and the mortality rate was significantly higher (17 [54.8%] vs. 15 [9.5%], p < .001). Among patients in ICU, the subjects with myocardial injury showed an increase need of endotracheal intubation (8 out of 9 [88%] vs 7 out of 19[37%], p = .042). Multivariate analyses showed that hs-TnI can significantly predict the degree of COVID-19 disease, the intubation need and in-hospital mortality.
Conclusions
In this study we demonstrate that hs-Tn can significantly predict disease severity, intubation need and in-hospital death. Therefore, it may be reasonable to use Hs-Tn as a clinical tool in COVID-19 patients in order to triage them into different risk groups and can play a pivotal role in the detection of subjects at high risk of cardiac impairment during both the early and recovery stage.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:278-285
Maino A, Di Stasio E, Grimaldi MC, Cappannoli L, ... Landolfi R, Biasucci LM
Int J Cardiol: 31 Aug 2021; 338:278-285 | PMID: 34157355
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Impact:
Abstract

Utility of single-shot compressed sensing cardiac magnetic resonance cine imaging for assessment of biventricular function in free-breathing and arrhythmic pediatric patients.

Zou Q, Xu HY, Fu C, Zhou XY, ... Yang ZG, Guo YK
Background
This study aimed to explore the feasibility and accuracy of single-shot compressed-sensing (CS) cardiac magnetic resonance cine technology for the assessment of biventricular function and morphology in free-breathing (FB) pediatrics, especially those with arrhythmia.
Methods
Seventy consecutive pediatric participants (6.27 ± 3.8 years, range:0.5-14 years) were enrolled between August 2019 and July 2020. Single-shot CS and conventional balanced steady-state free-precession (bSSFP) cine were obtained. The total scanning time, image quality and biventricular function parameters were compared for both sequences.
Results
Single-shot CS cine had shorter acquisition time compared with the conventional bSSFP cine (all P < 0.001). The single-shot CS cine also had fewer artifacts than conventional bSSFP cine (breath-hold (BH): 4.6 ± 0.6 vs. 4.3 ± 0.6; FB without ongoing arrhythmia: 4.5 ± 0.6 vs. 3.6 ± 0.9; FB with ongoing arrhythmia: 4.7 ± 0.5 vs. 2.6 ± 1.1; all P < 0.05). No statistical difference of left ventricular parameters and right ventricular end-systolic volume/ejection fraction were found between the single-shot CS and conventional bSSFP cine in both BH and FB without ongoing arrhythmia group. There was an excellent correlation (R2 = 0.60-0.98, all P < 0.001) and good intra-(range: R2 = 0.57-0.99, P < 0.001)/inter-observer agreements (range: R2 = 0.76-1, P < 0.001) for single-shot CS cine images in terms of biventricular function parameters.
Conclusions
The single-shot CS cine can significantly reduce the image acquisition time, offering reliable quantification of biventricular function in free breathing condition for arrhythmic patients.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:258-264
Zou Q, Xu HY, Fu C, Zhou XY, ... Yang ZG, Guo YK
Int J Cardiol: 31 Aug 2021; 338:258-264 | PMID: 34181995
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Impact:
Abstract

Acute thrombogenicity of fluoropolymer coated stents versus competitive drug-eluting stents under single antiplatelet therapy.

Sato Y, Jinnouchi H, Kolodgie FD, Cheng Q, ... Virmani R, Finn AV
Background
Recent clinical studies have suggested the feasibility of 1-month dual antiplatelet therapy (DAPT) for patients receiving drug-eluting stent (DES). Although our previous ex-vivo swine arteriovenous (AV) shunt studies under low dose heparin treatment suggested superior thromboresistance of fluoropolymer-coated everolimus-eluting stent (FP-EES) when compared to other polymer-based DESs, the relative thromboresistance of different DESs under single antiplatelet therapy (SAPT) has never been examined. This study aimed to evaluate platelet adhesion under SAPT in competitive DESs in the in vitro flow loop model and ex vivo swine AV shunt model.
Methods
The thrombogenicity of FP-EES, BioLinx polymer zotarolimus-eluting stent (BL-ZES), and biodegradable polymer everolimus-eluting stent (BP-EES) was assessed acutely using the swine AV shunt model under aspirin or clopidogrel SAPT. Stents were immunostained using antibodies against platelets and inflammatory markers and evaluated by confocal microscopy. Also, the adhesion of platelet and albumin on the three DESs was assessed by an in-vitro flow loop model using human platelets under aspirin SAPT and fluorescent albumin, respectively.
Results
In the shunt model, FP-EES showed significantly less platelet and inflammatory cell adhesion than BL-ZES and BP-EES. In the flow loop model, FP-EES showed significantly less platelet coverage and more albumin adsorption than BL-ZES and BP-EES.
Conclusions
These results suggest FP-EES may have particular advantage for short-term DAPT compared to other DESs.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:42-49
Sato Y, Jinnouchi H, Kolodgie FD, Cheng Q, ... Virmani R, Finn AV
Int J Cardiol: 31 Aug 2021; 338:42-49 | PMID: 34174338
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Impact:
Abstract

Optimal hemostasis duration for percutaneous coronary intervention via the snuffbox approach: A prospective, multi-center, observational study (HEMOBOX).

Roh JW, Kim Y, Takahata M, Shiono Y, ... Jeong MH, Akasaka T
Background
Percutaneous coronary intervention (PCI) via the distal radial access (DRA), called as snuffbox approach, recently has been increased worldwide due to fewer complications. Generally, since the diameter of distal radial artery is smaller than the radial artery, it is expected that the hemostasis duration can be shortened; however, there are no prospective studies. Furthermore, there is a lack of data about the feasibility of DRA for PCI.
Methods
We prospectively collected data from 250 patients who were performed PCI via the DRA by three multi-center operators between March 2019 and December 2019. The primary outcome was hemostasis duration. Secondary outcomes were success rate of PCI, cannulation time, and puncture site complications.
Results
Mean age of study population was 65.1 ± 10.3 years, success rate of PCI via the DRA was 99.2% (250/252) and 91.2% (228/250) patients was performed PCI via 6-French sheath. The cannulation time was 131 ± 98 s and the average hemostasis duration was 199 ± 50 min, and the median time was 180 [180-200] min. There are few minor hematomas (8.0%) and puncture site numbness (1.6%) with no radial artery occlusion.
Conclusions
HEMOBOX trial first reported hemostasis duration for PCI using the DRA, approximately 3 h, with 99.2% success rate and few minor complications.
Trial registration
https://clinicaltrials.gov/ct2/show/NCT03863652.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Aug 2021; 338:79-82
Roh JW, Kim Y, Takahata M, Shiono Y, ... Jeong MH, Akasaka T
Int J Cardiol: 31 Aug 2021; 338:79-82 | PMID: 34171449
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Impact:
Abstract

Obese patients\' characteristics and weight loss outcomes in cardiac rehabilitation: An observational study of registry data.

Wilkinson JA, Harrison AS, Doherty P
Aim
Cardiac rehabilitation (CR) guidelines advocate weight loss for obese patients but mean weight loss is small. We sought to determine the extent to which obese patients\' characteristics prior to CR predict weight loss.
Methods
An observational, pre- and post CR study of routine practice using the UK National Audit of Cardiac Rehabilitation dataset was undertaken. Backward, stepwise, multiple linear regression analysis was used to identify characteristics prior to CR that predicted weight change in obese patients.
Results
In 29,601 obese patients undertaking CR, mean weight loss was 0.9 kg (SD 4.3; p < 0.001) in men (74% of sample) and 0.5 kg (SD 3.9; p < 0.001) in women. Smoking cessation since the cardiac event independently predicted less weight loss by 1.2 kg (95% CI; 0.9, 1.5 kg; p < 0.001). Diabetes, cardiac surgery, living in a deprived area, being female, low fitness levels and pain independently predicted less weight loss during CR. Higher initial weight, greater age and being employed predicted increased weight loss.
Conclusion
This is the first study to identify how the characteristics of obese patients independently predict different amounts of weight loss during CR in free-living individuals. It is also the largest, registry-based study to investigate predictors of weight loss in obese patients in CR. Knowledge of the extent to which obese patients\' characteristics predict more or less weight loss can aid: the generation of guidelines; agreement of realistic goals with patients; and tailoring of weight management support.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Aug 2021; 337:16-20
Wilkinson JA, Harrison AS, Doherty P
Int J Cardiol: 14 Aug 2021; 337:16-20 | PMID: 33940094
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Impact:
Abstract

Risk stratification of cardiovascular complications using CHADS-VASc and CHADS scores in chronic atherosclerotic cardiovascular disease.

Sen J, Tonkin A, Varigos J, Fonguh S, ... Amerena J, COMPASS Trial Investigators

Background:
The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that rivaroxaban plus aspirin reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD). We explored whether CHA2DS2-VASc or CHADS2 scores, well-validated tools for assessing risk of thromboembolic events in atrial fibrillation, can identify vascular patients at highest risk of recurrent events who may derive greatest benefits of treatment. Methods Predictive accuracies of the CHA2DS2-VASc and CHADS2 scores for MACE, were assessed in this analysis of the COMPASS trial. Kaplan-Meier estimates of cumulative risk were used to compare the effects of rivaroxaban plus aspirin (n = 9152) with aspirin alone (n = 9126) according to risk scores. Results High CHA2DS2-VASc (6-9) or CHADS2 (3-6) scores were associated with over three times greater absolute risk of MACE compared with CHA2DS2-VASc score of 1-2 or CHADS2 score of 0. The effects of rivaroxaban plus aspirin compared with aspirin alone were consistent across CHA2DS2-VASc and CHADS2 score categories for MACE, bleeding and net clinical benefit, with greatest reduction in MACE observed in patients treated for 30 months with highest CHADS2 score (3-6) (hazard ratio = 0.67, 95% CI: 0.53-0.86, p = 0.0012, 25 events per 1000 patients prevented).
Conclusion:
The CHA2DS2-VASc and CHADS2 scores can be used in patients with chronic CAD and/or PAD to identify patients who are at highest risk of MACE. Those identified at highest risk by CHADS2 scores had greatest benefit from dual pathway inhibition with rivaroxaban plus aspirin. Clinical Trial Registration: NCT01776424.


Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 Aug 2021; 337:9-15
Sen J, Tonkin A, Varigos J, Fonguh S, ... Amerena J, COMPASS Trial Investigators
Int J Cardiol: 14 Aug 2021; 337:9-15 | PMID: 33957178
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Impact:
Abstract

Hydroxychloroquine reduces interleukin-6 levels after myocardial infarction: The randomized, double-blind, placebo-controlled OXI pilot trial.

Ulander L, Tolppanen H, Hartman O, Rissanen TT, ... Eklund KK, Sinisalo J
Objectives
To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction.
Method
In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months.
Results
The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to interruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups).
Conclusions
In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocardial infarction.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Aug 2021; 337:21-27
Ulander L, Tolppanen H, Hartman O, Rissanen TT, ... Eklund KK, Sinisalo J
Int J Cardiol: 14 Aug 2021; 337:21-27 | PMID: 33961943
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Impact:
Abstract

Stratified medicine using invasive coronary function testing in angina: A cost-effectiveness analysis of the British Heart Foundation CorMicA trial.

Heggie R, Briggs A, Stanley B, Good R, ... Ford TJ, Berry C
Aim
Coronary angiography is indicated in many patients with known or suspected angina for the investigation of coronary artery disease (CAD). However, up to half of patients with symptoms of ischaemia have no obstructive coronary arteries (INOCA). This large subgroup includes patients with suspected microvascular angina (MVA) and/or vasospastic angina (VSA). Clinical guidelines relating to the management of patients with INOCA are limited. Uncertainty regarding the diagnosis of patients with INOCA presents a health economic challenge, both in terms of healthcare resource utilisation and of quality-of-life impact on patients.
Methods
A cost-effectiveness analysis of the introduction of stratified medicine into the invasive management of INOCA, based on clinical and resource-use data obtained in the CorMicA trial, from a UK NHS perspective. The intervention included an invasive diagnostic procedure (IDP) of coronary vascular function during coronary angiography to define clinical endotypes to target with linked medical therapy. Outcomes of interest were mean total cost and QALY gain between treatment groups, and the incremental cost-effectiveness ratio. We undertook probabilistic sensitivity and scenario analyses.
Results
The incremental cost per QALY gained at 12 months was £4500 (£2937, £33264). Compared with a willingness-to-pay (WTP) threshold of £20,000 per QALY, the use of the IDP test is cost-effective. At this WTP threshold there is a 96% probability of the IDP being cost-effective, based on the uncertainty described by bootstrap analysis.
Conclusions
The burden of INOCA, particularly in women, is known to be significant. These findings provided new evidence to inform this unmet clinical need.

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Aug 2021; 337:44-51
Heggie R, Briggs A, Stanley B, Good R, ... Ford TJ, Berry C
Int J Cardiol: 14 Aug 2021; 337:44-51 | PMID: 33992700
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Impact:
Abstract

A prospective study on the incidence of contrast-associated acute kidney injury after recanalization of chronic total coronary occlusions with contemporary interventional techniques.

Werner GS, Lorenz S, Yaginuma K, Koch M, ... Moehlis H, Riegel W
Background
Contrast-associated acute kidney injury (CA-AKI) is a potential risk associated with the percutaneous coronary interventions (PCI) for chronic total coronary occlusions (CTO). This study should evaluate the incidence of CA-AKI in an era of advanced strategies of recanalization techniques and identify modifiable determinants.
Methods
We analysed 1924 consecutive CTO procedures in 1815 patients between 2012 and 2019. All patients were carefully monitored at least up to 48 h after a CTO procedure for changes in renal function.
Results
The incidence of CA-AKI was 5.6%, but there was no relation to the technical approach such as frequency of the retrograde technique, intravascular ultrasound or radial access. Procedures with CA-AKI had longer fluoroscopy times (37.6 vs 46.1 min; p = 0.005). The major determinants of CA-AKI were age, presence of diabetes and reduced ejection fraction, as well as chronic kidney disease stage ≥2, serum haemoglobin, and fluoroscopy time. Contrast volume or contrast volume/GFR ratio were not independent determinants of CA-AKI. Periprocedural perforations were more frequent in CA-AKI patients (11.3 vs 2.3%; p < 0.001), and in-hospital mortality was higher (2.8 vs 0.4%; p < 0.001).
Conclusions
CA-AKI was associated with the risk of in-hospital adverse events. Established patient-related risk factors for CA-AKI (age, diabetes, preexisting chronic kidney disease, low ejection fraction) were confirmed in this study. In addition, the length of the procedure, coronary perforations and low preprocedural serum haemoglobin were risk factors that might be preventable in patients at high risk for CA-AKI.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Aug 2021; 337:38-43
Werner GS, Lorenz S, Yaginuma K, Koch M, ... Moehlis H, Riegel W
Int J Cardiol: 14 Aug 2021; 337:38-43 | PMID: 34015410
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Impact:
Abstract

Safety and efficacy of coronary sinus narrowing in chronic refractory angina: Insights from the RESOURCE study.

Ponticelli F, Khokhar AA, Leenders G, Konigstein M, ... Banai S, Giannini F
Introduction
Refractory angina (RA) is considered the end-stage of coronary artery disease, and often has no interventional treatment options. Coronary sinus Reducer (CSR) is a recent addition to the therapeutic arsenal, but its efficacy has only been evaluated on small populations. The RESOURCE registry provides further insights into this therapy.
Methods
The RESOURCE is an observational, retrospective registry that includes 658 patients with RA from 20 centers in Europe, United Kingdom and Israel. Prespecified endpoints were the amelioration of anginal symptoms evaluated with the Canadian Cardiovascular Society (CCS) score, the rates of procedural success and complications, and MACEs as composite of all-cause mortality, acute coronary syndromes, and stroke.
Results
At a median follow-up of 502 days (IQR 225-1091) after CSR implantation, 39.7% of patients improved by ≥2 CCS classes (primary endpoint), and 76% by ≥1 class. Procedural success was achieved in 96.7% of attempts, with 3% of procedures aborted mostly for unsuitable coronary sinus anatomy. Any complication occurred in 5.7% of procedures, but never required bailout surgery nor resulted in intra- or periprocedural death or myocardial infarction. One patient developed periprocedural stroke after inadvertent carotid artery puncture. At the last available follow-up, overall mortality and MACE were 10.4% and 14.6% respectively. At one, three and five years, mortality rate at Kaplan-Meier analysis was 4%, 13.7%, and 23.4% respectively.
Conclusions
CSR implantation is safe and reduces angina in patients with refractory angina.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Aug 2021; 337:29-37
Ponticelli F, Khokhar AA, Leenders G, Konigstein M, ... Banai S, Giannini F
Int J Cardiol: 14 Aug 2021; 337:29-37 | PMID: 34029618
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Impact:
Abstract

External validation of the increased wall thickness score for the diagnosis of cardiac amyloidosis.

Monda E, Palmiero G, Lioncino M, Rubino M, ... Dongiglio F, Limongelli G
Introduction
This study aimed to validate the increased wall thickness (IWT) score, a multiparametric echocardiographic score to facilitate diagnosis of cardiac amyloidosis (CA), in an independent population of patients with increased LV wall thickness suspicious for CA.
Methods
Between January 2019 and December 2020, 152 consecutive patients with increased LV wall thickness suspicious for CA were included. For all patient, the multiparametric echocardiographic score (IWT score) was calculated. To validate the diagnostic accuracy of an IWT score ≥ 8 to predict the diagnosis of CA, sensibility (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and predictive accuracy (PA) were calculated.
Results
Among the 152 patients included in the study, 50 (33%) were diagnosed as CA, 25 (16%) had severe aortic stenosis, 25 (16%) had hypertensive remodeling, and 52 (34%) had hypertrophic cardiomyopathy. Among the 50 and 102 patients with and without CA, 19 (38%) and 1 (1%) showed an IWT score ≥ 8, respectively. Overall, the diagnostic accuracy of an IWT score ≥ 8 for the diagnosis of CA in our population was the following: Se 38% (95%CI 25-53%); Sp 99% (95%CI 95-100%); PPV 95% (95%CI 72-99%); NPV 77% (95%CI 73-80%); PA 79% (95%CI 72-85%).
Conclusions
This study reports the first external validation of the IWT score for the diagnosis of CA in patients with increased LV wall thickness. A score ≥ 8 showed a high Sp, PPV and PA, suggesting that the IWT score can be used to identify CA patients in those with increased LV wall thickness.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 17 Jul 2021; epub ahead of print
Monda E, Palmiero G, Lioncino M, Rubino M, ... Dongiglio F, Limongelli G
Int J Cardiol: 17 Jul 2021; epub ahead of print | PMID: 34289405
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Impact:
Abstract

Clinical history and gastrointestinal bleeding in patients taking oral anticoagulants.

Doris B, Fenu L, Marongiu F
Background
Common risk factors for gastrointestinal bleeding (GIB) are advanced age and the use of antiplatelet or anticoagulants drugs for the prevention of cardiovascular diseases.
Methods
In this prospective real-world observational study, oral anticoagulated patients were recruited and followed between June 2013 and December 2019. The primary end-point was to evaluate a possible relationship between bleeding events and patients\' clinical history of gastrointestinal disease prior to the start of the therapy. The secondary end-points were time of GIB appearance and the percentage of idiopathic or provoked events, i.e., bleeding due to a gastrointestinal disease. In case of GIB event all the patients were studied by means of endoscopic procedures. Cox regression was used to calculate the relative hazard ratios (HRs) of GIB for each considered clinical variable.
Results
734 patients on both VKAs or DOACs were studied. Overall, 46 hemorrhagic events were recorded: 6 were major bleeding (0.42/100 patient-years) while 43 were clinically relevant non major bleeding (2.8/100 patient-years). The Cox regression analysis did not show any relationships among GIB and the variables considered.
Conclusion
The patients\' clinical history is neither a predictor for GIB bleeding nor a guide to the choice of the oral anticoagulant to be administered. Routinely applying bleeding risk screening, such as occult blood in the stool, should be added to the periodic laboratory checks for early recognition of patients at higher risk of GIB.

Copyright © 2018. Published by Elsevier B.V.

Int J Cardiol: 15 Jul 2021; epub ahead of print
Doris B, Fenu L, Marongiu F
Int J Cardiol: 15 Jul 2021; epub ahead of print | PMID: 34280423
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Impact:
Abstract

ECG-based score estimates the probability to detect Fabry Disease cardiac involvement.

Figliozzi S, Camporeale A, Boveri S, Pieruzzi F, ... Namdar M, Lombardi M
Objectives
To elaborate an ECG-based nomogram estimating the probability to detect cardiac involvement by cardiac magnetic resonance (CMR) in Fabry Disease (FD).
Methods
119 FD patients and 26 healthy controls underwent ECG and CMR. Test (n = 88, 60%) and validation cohorts (n = 57, 40%) were randomly derived. Cardiac involvement was defined as the presence of low myocardial T1 value, a CMR-surrogate of myocardial glycosphingolipid storage. ECG changes associated with low T1 value were identified in the test cohort, included in the nomogram and then tested in the validation cohort.
Results
Sokolow-Lyon index (AUC = 0.769), ratio between P-wave and PR-segment durations (Pwave/PRsegment) (AUC = 0.778), QRS duration (AUC = 0.703), QT (AUC = 0.769) duration were independently associated with the presence of low T1 on CMR at multivariate analysis. An ECG-based nomogram including these four parameters was accurate in identifying patients with CMR evidence of glycosphingolipid storage (c-index of the derived-nomogram = 0.90 in the test group; 0.81 in the validation group).
Conclusion
We propose a practical ECG-based nomogram accurately estimating the probability to detect low T1 values by CMR in FD patients. The application of this tool in clinical practice could improve early detection of FD cardiac involvement.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 Jul 2021; epub ahead of print
Figliozzi S, Camporeale A, Boveri S, Pieruzzi F, ... Namdar M, Lombardi M
Int J Cardiol: 14 Jul 2021; epub ahead of print | PMID: 34274410
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Impact:
Abstract

Impact of right ventricular systolic function in patients with significant tricuspid regurgitation. A cardiac magnetic resonance study.

Hinojar R, Gómez AG, García-Martin A, Monteagudo JM, ... Zamorano JL, Fernández-Golfín C
Background
Right ventricle (RV) dilatation and dysfunction are established criteria for intervention in severe tricuspid regurgitation (TR); however thresholds to support intervention are lacking. New measures of RV function such as RV shortening (RVS) and effective RV ejection fraction (eRVEF) may be earlier markers of RV dysfunction.
Purpose
to compare the prognostic impact of different parameters of RV function and to describe cut-off values of RV size/function and TR severity of poor prognosis.
Methods
Consecutive patients evaluated in the Heart Valve Clinic with significant TR (severe, massive or torrential TR) undergoing a CMR study were included. In addition to parameters of biventricular volume and function, RVS and eRVEF were assessed. A combined endpoint of hospital admission due to right heart failure and cardiovascular mortality was defined.
Results
75 patients were included (age 75 ± 8 years, female 75%). During a median follow-up of 3 years (IQR: 1.4-3.9 years), 39% experienced the endpoint. Cut-off values of worse prognosis were: RVS ≥ -14%, eRVEF ≤34%, RVEF ≤58%, RV-EDV ≥100 ml/m2, TR regurgitant fraction (TRF) ≥40% and TR volume ≥ 42 ml. RVS and eRVEF identified higher rates of RV dysfunction than RVEF. After adjustment for age and LVEF, both eRVEF ≤34% (HR: 5.29 [2.25-12.4]) and RVS ≥ -14% (HR: 3.46 [1.13-9.17]) were significantly associated with outcomes. Among all parameters of RV function, eRVEF was the strongest predictor of outcomes, incremental to RVEF (ΔC-statistic 0.139 [0.040-0.237], p = 0.005). Patients with eRVEF ≤34% and RV-EDV ≥100 ml/m2 or eRVEF ≤34% and TRF ≥40% had the worst prognosis (p < 0.01 for both).
Conclusion
RVS and eRVEF identify higher rates of RV dysfunction beyond RVEF. Among all measures, eRVEF held the strongest association with outcomes, incremental to RVEF.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 13 Jul 2021; epub ahead of print
Hinojar R, Gómez AG, García-Martin A, Monteagudo JM, ... Zamorano JL, Fernández-Golfín C
Int J Cardiol: 13 Jul 2021; epub ahead of print | PMID: 34273433
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Impact:
Abstract

Medical management of anginal symptoms in women with stable angina pectoris: A systematic review of randomised controlled trials.

Webb CM, Collins P
Background
Medical therapies are used to improve stable anginal symptoms and quality of life in clinical practice however the evidence for the use of antianginal medication in women is largely unknown. We conducted a systematic review to investigate the extent of the evidence-base for the medical management of anginal symptoms in women with stable angina.
Methods
MEDLINE, EMBASE, Cochrane and ClinicalTrials.gov databases were searched to the end of December 2019. Retrieved papers were hand searched. Included were randomised controlled trials with at least one week of follow-up that included women with stable angina pectoris, with or without significant coronary atherosclerosis, randomised to conventional antianginal medication or/and a comparator, with a primary or secondary endpoint of angina frequency or glyceryl trinitrate (GTN) consumption.
Results
A total of 397 eligible publications were included in a qualitative analysis, with women comprising up to 20-30% of the study populations. No publication that included women and men reported all data separately for each sex. Twenty-six publications reported any female data separately from male data but only 18 reported angina data for women, 12 of which included fewer than 10 women.
Conclusions
Substantially fewer women than men were included in randomised trials of antianginal medications reporting effects on anginal symptoms, and reporting of data by sex was infrequent. As a result, there is little evidence on which to base treatment recommendations for anginal symptoms in women. Our results provide a platform for future studies to fill this void in the evidence.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 13 Jul 2021; epub ahead of print
Webb CM, Collins P
Int J Cardiol: 13 Jul 2021; epub ahead of print | PMID: 34273431
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Impact:
Abstract

Prediction of 1-year mortality after heart transplantation using machine learning approaches: A single-center study from China.

Zhou Y, Chen S, Rao Z, Yang D, ... Dong N, Li F
Background
Heart transplantation (HTx) remains the gold-standard treatment for end-stage heart failure. The aim of this study was to establish a risk-prediction model for assessing prognosis of HTx using machine-learning approach.
Methods
Consecutive recipients of orthotopic HTx at our institute between January 1st, 2015 and December 31st, 2018 were included in this study. The primary outcome was 1-year mortality. Least absolute shrinkage and selection operator method was used to select variables and seven different machine-learning approaches were employed to develop the risk-prediction model. Bootstrap method was used for model validation. Shapley Additive exPlanations (SHAP) method was used for model interpretation.
Results
381 recipients were included with average age of 43.783 years old. Albumin, recipient age and left atrium diameter ranked top three most important variables that affected the 1-year mortality of HTx. Other important variables included red blood cell, hemoglobin, lymphocyte%, smoking history, use of lyophilized rhBNP, use of Levosimendan, hypertension, cardiac surgery history, malignancy and endotracheal intubation history. Random Forest (RF) model achieved the best area under curves (AUC) of 0.801 and gradient boosting machine (GBM) showed the best sensitivity of 0.271. SHAP method was introduced to display the RF model\'s predicting processes of \"survival\" or \"death\" in individual level.
Conclusions
We established the risk-prediction model for postoperative prognosis of HTx patients by using machine learning method and demonstrated that the RF model performed the highest discrimination with the largest AUC when validated. This prediction model could help to recognize high-risk HTx recipients, provide personalized therapy plan and reduce organ wastage.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 12 Jul 2021; epub ahead of print
Zhou Y, Chen S, Rao Z, Yang D, ... Dong N, Li F
Int J Cardiol: 12 Jul 2021; epub ahead of print | PMID: 34271025
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Impact:
Abstract

Impact of in-stent tissue characteristics on excimer laser coronary angioplasty prior to drug-coated balloon treatment.

Ishihara T, Dohi T, Nakamura D, Kikuchi A, ... Sakata Y, QUEST Investigators
Background
Percutaneous coronary intervention with drug-coated balloon (DCB) angioplasty is one of the standard treatments for lesions with in-stent restenosis (ISR). However, the efficacy of additional excimer laser coronary angioplasty (ELCA) for ISR lesions prior to DCB angioplasty has not been elucidated. The aims of this study were to elucidate the efficacy of ELCA prior to DCB treatment for ISR and the difference in effectiveness by lesion morphology.
Methods
This was a multicenter, retrospective observational study. We enrolled 208 ISR lesions from 204 patients which were treated with DCB angioplasty under optical coherence tomography (OCT) guidance. We compared the acute gain evaluated by quantitative coronary angiography and clinically driven target lesion revascularization (CD-TLR) between the ELCA (+) (47 lesions) and ELCA (-) (161 lesions) groups.
Results
The acute gain was significantly larger in the ELCA (+) group (1.51 ± 0.47 mm versus 1.29 ± 0.52 mm, P = 0.012). Even after adjustment for comorbidities, the ELCA had a significant impact on the acute gain (coefficient 0.24 [95% confidence interval 0.067-0.41]). In addition, the ELCA usage was significantly associated with larger acute gain in lesions with a homogeneous pattern, although there was no association between ELCA and either the heterogeneous pattern or neoatherosclerosis. The freedom from CD-TLR was not different between the ELCA (-) and ELCA (+) groups (hazard ratio 0.53 [0.24-1.18]).
Conclusions
ELCA had a significant impact on the larger acute gain in ISR lesions, especially may did in those with a homogenous pattern, while it did not impact CD-TLR significantly.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 11 Jul 2021; epub ahead of print
Ishihara T, Dohi T, Nakamura D, Kikuchi A, ... Sakata Y, QUEST Investigators
Int J Cardiol: 11 Jul 2021; epub ahead of print | PMID: 34265314
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Impact:
Abstract

Platelet derived growth factor-A (Pdgf-a) gene transfer modulates scar composition and improves left ventricular function after myocardial infarction.

Rashid FN, Clayton ZE, Ogawa M, Perdomo J, ... Kizana E, Chong JJH
Background
Novel therapies that can limit or reverse damage caused by myocardial infarction (MI) could ease the increasing burden of heart failure. In this regard Platelet Derived Growth Factor (PDGF) has been previously shown to contribute to cardiac repair after MI. Here, we use a rodent model of MI and recombinant adeno-associated virus 9 (rAAV9)-mediated gene transfer to overexpress Pdgf-a in the injured heart and assess its therapeutic potential.
Methods and results
Sprague Dawley rats underwent temporary occlusion of the left anterior descending coronary artery, followed immediately by systemic delivery of 1 × 10^11 vector genomes of either rAAV9 Pdgf-a or rAAV9 Empty vector (control). At day 28 post-MI echocardiography showed significantly improved left ventricular (LV) function (fractional shortening) after rAAV9 Pdgf-a (0.394 ± 0.019%) treatment vs control (0.304 ± 0.018%). Immunohistochemical analysis demonstrated significantly increased capillary and arteriolar density in the infarct border zone of rAAV9 Pdgf-a treated hearts together with a significant reduction in infarct scar size (rAAV9 Pdgf-a 6.09 ± 0.94% vs Empty 12.45 ± 0.92%). Western blot and qPCR analyses confirmed overexpression of PDGF-A and showed upregulation of smooth muscle alpha actin (Acta2), collagen type III alpha 1 (Col3a1) and lysyl oxidase (Lox) genes in rAAV9 Pdgf-a treated infarcts.
Conclusion
Overexpression of Pdgf-a in the post-MI heart can modulate scar composition and improve LV function. Our study highlights the potential of rAAV gene transfer of Pdgf-a as a cardio-reparative therapy.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 11 Jul 2021; epub ahead of print
Rashid FN, Clayton ZE, Ogawa M, Perdomo J, ... Kizana E, Chong JJH
Int J Cardiol: 11 Jul 2021; epub ahead of print | PMID: 34265313
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Impact:
Abstract

Design and rationale of a clinical trial to increase cardiomyocyte division in infants with tetralogy of Fallot.

El Khoudary SR, Fabio A, Yester JW, Steinhauser ML, ... Groscost DK, Kühn B
Background
Patients with Tetralogy of Fallot with pulmonary stenosis (ToF/PS), the most common form of cyanotic congenital heart disease (CHD), develop adverse right ventricular (RV) remodeling, leading to late heart failure and arrhythmia. We recently demonstrated that overactive β-adrenergic receptor signaling inhibits cardiomyocyte division in ToF/PS infants, providing a conceptual basis for the hypothesis that treatment with the β-adrenergic receptor blocker, propranolol, early in life would increase cardiomyocyte division. No data are available in ToF/PS infants on the efficacy of propranolol as a possible novel therapeutic option to increase cardiomyocyte division and potentially reduce adverse RV remodeling.
Methods
Using a randomized, double-blind, placebo-controlled trial, we will evaluate the effect of propranolol administration on reactivating cardiomyocyte proliferation to prevent adverse RV remodeling in 40 infants with ToF/PS. Propranolol administration (1 mg/kg po QID) will begin at 1 month of age and last until surgical repair. The primary endpoint is cardiomyocyte division, quantified after 15N-thymidine administration with Multi-isotope Imaging Mass Spectrometry (MIMS) analysis of resected myocardial specimens. The secondary endpoints are changes in RV myocardial and cardiomyocyte hypertrophy.
Conclusion
This trial will be the first study in humans to assess whether cardiomyocyte proliferation can be pharmacologically increased. If successful, the results could introduce a paradigm shift in the management of patients with ToF/PS from a purely surgical approach, to synergistic medical and surgical management. It will provide the basis for future multi-center randomized controlled trials of propranolol administration in infants with ToF/PS and other types of CHD with RV hypertension.
Clinical trial registration
The trial protocol was registered at clinicaltrials.gov (NCT04713657).

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 11 Jul 2021; epub ahead of print
El Khoudary SR, Fabio A, Yester JW, Steinhauser ML, ... Groscost DK, Kühn B
Int J Cardiol: 11 Jul 2021; epub ahead of print | PMID: 34265312
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Impact:
Abstract

Upper extremities deep vein thrombosis treated with oral direct anticoagulants: A prospective cohort study.

Vedovati MC, Tratar G, Mavri A, Mazzetti M, ... Agnelli G, Becattini C
Background
Limited data are available on the role of direct oral anticoagulants (DOACs) for the treatment of upper extremities deep vein thrombosis (UEDVT).
Objectives
The aim of this study was to assess the effectiveness and safety of DOACs in the treatment of UEDVT.
Methods
Patients with an objectively confirmed acute UEDVT treated with DOACs were merged from prospective cohorts to a collaborative database. Primary study outcomes were recurrent venous thromboembolism (VTE) and major bleeding occurring during DOAC treatment.
Results
Overall, 188 patients were included in the study: mean age 52.4 ± 20.4 years, males 43.6%, patients with active cancer 29.2%. Twenty-nine percent of patients had 2 or more risk factors for VTE, 33.0% had catheter-related or pacemaker-related UEDVT. In 13.8% of patients, DOACs were started one month after UEDVT diagnosis or later. Active cancer was an independent predictor for delayed initiation of DOACs (OR 8.1, 95% CI 3.0-22.2). Mean duration of treatment with DOACs was 5.1 ± 2.8 months. During treatment with DOACs, recurrent VTE occurred in 0.9 per 100 patient-year, major bleeding in 1.7 and all-cause deaths in 6.0 per 100 patient-year. No fatal bleeding or fatal VTE recurrence were observed. During 232.1 patient-years of follow-up after DOAC withdrawal, recurrent VTE occurred in 3.0 per 100 patient-year. The 2019 ESC categories for risk of VTE recurrences were able to discriminate patient groups at different risk of events in the on and off-treatment periods.
Conclusions
Our data support the feasibility as well as the effectiveness and safety of DOACs for the treatment of acute UEDVT.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 07 Jul 2021; epub ahead of print
Vedovati MC, Tratar G, Mavri A, Mazzetti M, ... Agnelli G, Becattini C
Int J Cardiol: 07 Jul 2021; epub ahead of print | PMID: 34245794
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Impact:
Abstract

Association between polyvascular disease and clinical outcomes in patients with cardiogenic shock: Results from the RESCUE registry.

Jang WJ, Park IH, Yang JH, Chun WJ, ... Jeong JO, Gwon HC
Background
Clinical implications of systemic atherosclerosis in patients with cardiogenic shock (CS) remain unclear. This study investigated the association between polyvascular disease (PVD) and clinical outcome in CS patients.
Methods
A total of 1247 CS patients was enrolled from the RESCUE registry, a multicenter, observational cohort between January 2014 and December 2018. They were divided into two groups according to presence of PVD, defined as ≥2 coexistence of coronary artery disease, peripheral arterial disease, or cerebrovascular disease. Primary outcome was all-cause death during 12 months of follow-up.
Results
136 (10.9%) patients were diagnosed with PVD. The risk of 12-month all-cause death was significantly higher in the PVD group than in the non-PVD group (54.4% versus 40.4%, adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.02-1.69, p = 0.034). There was a significant interaction between PVD and vasoactive inotropic score (VIS) (p for interaction = 0.014). Among the 945 patients with VIS <84, PVD was associated with a higher risk of 12-month all-cause death (unadjusted HR 1.77, 95% CI 1.30-2.41, p = 0.030); among the 302 patients with VIS ≥84, the incidence of 12-month all-cause death was similar between the PVD and non-PVD groups (unadjusted HR 1.03, 95% CI 0.68-1.56, p = 0.301).
Conclusions
Presence of PVD was associated with 12-month all-cause mortality in patients with CS, especially for less severe forms of CS patients with VIS <84. Clinicaltrials.govnumber:NCT02985008.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 07 Jul 2021; epub ahead of print
Jang WJ, Park IH, Yang JH, Chun WJ, ... Jeong JO, Gwon HC
Int J Cardiol: 07 Jul 2021; epub ahead of print | PMID: 34246725
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Abstract

Association of heart failure subtypes and atrial fibrillation: Data from the Atherosclerosis Risk in Communities (ARIC) study.

Nji MAM, Solomon SD, Chen LY, Shah AM, ... Subramanya V, Alonso A
Aims
To determine the prevalence and incidence of AF among HF subtypes in a biracial community-based cohort.
Methods
We studied 6496 participants in the Atherosclerosis Risk in Community study (mean age, 75.8 ± 5.3, 59% women, 23% black) who attended the 2011-2013 visit. HF was identified from physician adjudicated diagnosis, hospital discharges, and self-report. HF subtypes were based on echocardiography. A left ventricular ejection fraction <40% represents HF with reduced ejection fraction (HFrEF), 40%-49% for HF with midrange ejection fraction (HFmEF), and ≥ 50% for HF with preserved ejection fraction (HFpEF). AF was ascertained through 2017 from study electrocardiograms, hospital discharges, and death certificates. Confounder-adjusted logistic regression and Cox models were used to estimate associations of HF subtype with prevalent and incident AF.
Results
Among eligible participants, 393 had HF (HFpEF = 232, HFmEF = 41, HFrEF = 35 and unclassified HF = 85) and 735 had AF. Compared to those without HF, all HF subtypes were more likely to have prevalent AF [odds ratio (95% confidence interval (CI)) 7.4 (5.6-9.9) for HFpEF, 8.1 (4.3-15.3) for HFmEF, 10.0 (5.0-20.2) for HFrEF, 8.8 (5.6-14.0) for unclassified HF]. Among participants without AF at baseline (n = 5761), 610 of them developed AF. Prevalent HF was associated with increased risk of AF [hazard ratio (95%CI) 2.3 (1.6-3.2) for HFpEF, 5.0 (2.7-9.3) for HFmEF, 3.5 (1.7-7.6) for HFrEF, 1.9 (0.9-3.7) for unclassified HF].
Conclusion
AF and HF frequently co-occur, with small differences by HF subtype, underscoring the importance of understanding the interplay of these two epidemics and evaluating shared preventive and therapeutic strategies.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 07 Jul 2021; epub ahead of print
Nji MAM, Solomon SD, Chen LY, Shah AM, ... Subramanya V, Alonso A
Int J Cardiol: 07 Jul 2021; epub ahead of print | PMID: 34246724
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Abstract

The effect of cardiac rhythm on artificial intelligence-enabled ECG evaluation of left ventricular ejection fraction prediction in cardiac intensive care unit patients.

Kashou AH, Noseworthy PA, Lopez-Jimenez F, Attia ZI, ... Friedman PA, Jentzer JC
The presence of left ventricular systolic dysfunction (LVSD) alters clinical management and prognosis in most acute and chronic cardiovascular conditions. While transthoracic echocardiography (TTE) remains the most common diagnostic tool to screen for LVSD, it is operator-dependent, time-consuming, effort-intensive, and relatively expensive. Recent work has demonstrated the ability of an artificial intelligence-augment ECG (AI-ECG) model to accurately predict LVSD in critical intensive care unit (CICU) patients. We demonstrate that the AI-ECG algorithm can maintain its performance in these patients with and without AF despite their clinical differences. An AI-ECG algorithm can serve as a non-invasive, inexpensive, and rapid screening tool for early detection of LVSD in resource-limited settings, and potentially expedite clinical decision making and guideline-directed therapies in the acute care setting.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 06 Jul 2021; epub ahead of print
Kashou AH, Noseworthy PA, Lopez-Jimenez F, Attia ZI, ... Friedman PA, Jentzer JC
Int J Cardiol: 06 Jul 2021; epub ahead of print | PMID: 34242690
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Abstract

Additional diagnostic value of cardiac magnetic resonance feature tracking in patients with biopsy-proven arrhythmogenic cardiomyopathy.

Muscogiuri G, Fusini L, Ricci F, Sicuso R, ... Guaricci AI, Pontone G
Background
We aim to evaluate the value of Cardiac magnetic resonance (CMR) feature tracking (CMR-FT) in addition to Task Force Criteria(TFC) in patients with (arrhythmogenic cardiomyopathy) AC biopsy-proved.
Methods
Thirty-five patients with AC histologically proven who performed CMR with late gadolinium enhancement (LGE) acquisition were enrolled. The study population was divided in Group1 (negative CMR TFC and LV ejection fraction≥55%) and Group2 (positive CMR TFC and/or LVEF<55%) and compared to an age and gender-matched control group. CMR datasets of all patients were analyzed to calculate LV indexed end-diastolic (LVEDi) and end-systolic (LVESi) volumes and RV indexed end-diastolic (RVEDi) and end-systolic (RVESi) volumes, both LV ejection fraction (LVEF) and RV ejection fraction (RVEF). Moreover, LV and RV global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain were measured.
Results
The AC patients showed both higher LVEDi (p:0.002) and RVEDi (p:0.017) and lower LVEF (p: 0.016) as compared to control patients. Moreover, AC patients showed impaired LV-GLS (p < 0.001), LV-GRS (p < 0.001), LV-GCS (p < 0.001) and RV-GRS (p:0.026) as compared to control subjects. Group1 patients showed a significant reduction of LV-GRS (p < 0.05) and LV-GCS p < 0.01) as compared to control subjects. At univariate analysis LV-GCS was the most discriminatory parameter between Group1 vs heathy subjects with an optimal cut-off of -15.8 (Sensitivity: 74%; Specificity: 10%).
Conclusions
In patients with AC biopsy-proven, CMR-FT could improve the diagnostic yield in the subset of patients who results negative for imaging TFC criteria resulting as useful gatekeeper for indication of myocardial biopsy in case of equivocal clinical and imaging presentation.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 06 Jul 2021; epub ahead of print
Muscogiuri G, Fusini L, Ricci F, Sicuso R, ... Guaricci AI, Pontone G
Int J Cardiol: 06 Jul 2021; epub ahead of print | PMID: 34242689
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Impact:
Abstract

Health-related quality of life and incident cardiovascular disease events in community-dwelling older people: A prospective cohort study.

Phyo AZZ, Ryan J, Gonzalez-Chica DA, Stocks NP, ... Freak-Poli R, ASPREE Investigator Group
Background
Lower health-related quality of life (HRQoL) has been shown to predict a higher risk of hospital readmission and mortality in patients with cardiovascular disease (CVD). Few studies have explored the associations between HRQoL and incident CVD. We explored the associations between baseline HRQoL and incident and fatal CVD in community-dwelling older people in Australia and the United States.
Methods
Longitudinal study using ASPirin in Reducing Events in the Elderly (ASPREE) trial data. This includes 19,106 individuals aged 65-98 years, initially free of CVD, dementia, or disability, and followed between March 2010 and June 2017. The physical (PCS) and mental component scores (MCS) of HRQoL were assessed using the SF-12 questionnaire. Incident major adverse CVD events included fatal CVD (death due to atherothrombotic CVD), hospitalizations for heart failure, myocardial infarction or stroke. Analyses were performed using Cox proportional-hazard regression.
Results
Over a median 4.7 follow-up years, there were 922 incident CVD events, 203 fatal CVD events, 171 hospitalizations for heart failure, 355 fatal or nonfatal myocardial infarction and 403 fatal or nonfatal strokes. After adjustment for sociodemographic, health-related behaviours and clinical measures, a 10-unit higher PCS, but not MCS, was associated with a 14% lower risk of incident CVD, 28% lower risk of hospitalization for heart failure and 15% lower risk of myocardial infarction. Neither PCS nor MCS was associated with fatal CVD events or stroke.
Conclusion
Physical HRQoL can be used in combination with clinical data to identify the incident CVD risk among older individuals.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 06 Jul 2021; epub ahead of print
Phyo AZZ, Ryan J, Gonzalez-Chica DA, Stocks NP, ... Freak-Poli R, ASPREE Investigator Group
Int J Cardiol: 06 Jul 2021; epub ahead of print | PMID: 34245793
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Impact:
Abstract

Association between acute myocardial infarction and death in 386 patients with a thrombus straddling a patent foramen ovale.

Shah P, Jimenez-Ruiz A, Gibson A, Vargas-González JC, ... Bagur R, Sposato LA
Backgorund
Right atrial thrombi are rarely found straddling a patent foramen ovale (PFO). A thrombus straddling a PFO (TSPFO), also known as impending paradoxical embolism, is a medical emergency associated with up to 11.5% risk of death within 24 h of being diagnosed. We hypothesized that acute myocardial infarction (MI) and ischemic stroke (IS) diagnosed upon the admission of patients with TSPFO are associated with increased risk of death. We also investigated if specific acute therapies are associated with reduced in-hospital mortality.
Methods
We performed a systematic search including case reports and series of adult patients with TSPFO published from 1950 to October 30, 2020. With gathered patient-level data and we applied a logistic regression model to evaluate on the risk of in-hospital death. We performed time-trends and several sensitivity analyses.
Results
We included 386 cases with a TSPFO comprised in 359 publications. The median age was 61 years and 51.2% were females. Fifty (13.0%) patients died during hospital stay, 82 (21.2%) had an acute IS, and 18 (4.6%) had an acute MI diagnosed upon admission. Acute MI (OR 7.83, 95%CI 2.70-22.7; P < 0.0001), but not IS, was associated with increased risk of death. Right atrial thrombectomy was associated with a 65% decreased in-hospital mortality (OR 0.35, 95%CI 0.18-0.70, P = 0.003). Results remained unchanged on sensitivity analyses.
Conclusion
In this systematic review of 386 cases of TSPFO, acute MI but not IS was associated with 8-fold increased risk of death, while surgical thrombectomy was associated with a significant 65% reduction of in-hospital mortality.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 06 Jul 2021; epub ahead of print
Shah P, Jimenez-Ruiz A, Gibson A, Vargas-González JC, ... Bagur R, Sposato LA
Int J Cardiol: 06 Jul 2021; epub ahead of print | PMID: 34245792
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Impact:
Abstract

A novel risk model for predicting potentially life-threatening arrhythmias in non-ischemic dilated cardiomyopathy (DCM-SVA risk).

Kayvanpour E, Sammani A, Sedaghat-Hamedani F, Lehmann DH, ... Asselbergs FW, Meder B
Background
Non-ischemic dilated cardiomyopathy (DCM) can be complicated by sustained ventricular arrhythmias (SVA) and sudden cardiac death (SCD). By now, left-ventricular ejection fraction (LV-EF) is the main guideline criterion for primary prophylactic ICD implantation, potentially leading either to overtreatment or failed detection of patients at risk without severely impaired LV-EF. The aim of the European multi-center study DETECTIN-HF was to establish a clinical risk calculator for individualized risk stratification of DCM patients.
Methods
1393 patients (68% male, mean age 50.7 ± 14.3y) from four European countries were included. The outcome was occurrence of first potentially life-threatening ventricular arrhythmia. The model was developed using Cox proportional hazards, and internally validated using cross validation. The model included seven independent and easily accessible clinical parameters sex, history of non-sustained ventricular tachycardia, history of syncope, family history of cardiomyopathy, QRS duration, LV-EF, and history of atrial fibrillation. The model was also expanded to account for presence of LGE as the eight8h parameter for cases with available cMRI and scar information.
Results
During a mean follow-up period of 57.0 months, 193 (13.8%) patients experienced an arrhythmic event. The calibration slope of the developed model was 00.97 (95% CI 0.90-1.03) and the C-index was 0.72 (95% CI 0.71-0.73). Compared to current guidelines, the model was able to protect the same number of patients (5-year risk ≥8.5%) with 15% fewer ICD implantations.
Conclusions
This DCM-SVA risk model could improve decision making in primary prevention of SCD in non-ischemic DCM using easily accessible clinical information and will likely reduce overtreatment.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 06 Jul 2021; epub ahead of print
Kayvanpour E, Sammani A, Sedaghat-Hamedani F, Lehmann DH, ... Asselbergs FW, Meder B
Int J Cardiol: 06 Jul 2021; epub ahead of print | PMID: 34245791
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Impact:
Abstract

Proinflammatory TH17 cytokine activation, disease severity and outcomes in peripartum cardiomyopathy.

Koczo A, Marino A, Rocco J, Ewald G, ... McNamara DM, IPAC Investigators
Background
Immune dysregulation is implicated in the development and clinical outcomes of peripartum cardiomyopathy (PPCM).
Methods and results
98 women with PPCM were enrolled and followed for 1 year postpartum (PP). LVEF was assessed at entry, 6-, and 12-months PP by echocardiography. Serum levels of soluble interleukin (IL)-2 receptor (sIL2R), IL-2, IL-4, IL-17, IL-22, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured by ELISA at entry. Cytokine levels were compared between women with PPCM by NYHA class. Outcomes including myocardial recovery and event-free survival were compared by cytokine tertiles. For cytokines found to impact survival outcomes, parameters indicative of disease severity including baseline LVEF, medications, and use of inotropic and mechanical support were analyzed. Levels of proinflammatory cytokines including IL-17, IL-22, and sIL2R, were elevated in higher NYHA classes at baseline. Subjects with higher IL-22 levels were more likely to require inotropic or mechanical support. Higher levels of TNF-α and IL-22 were associated with poorer event-free survival. Higher TNF-α levels were associated with lower mean LVEF at entry and 12 months. In contrast, higher levels of immune-regulatory cytokines such as IL-4 and IL-2 were associated with higher LVEF during follow up.
Conclusion
Proinflammatory cytokines IL-22 and TNF-α were associated with adverse event-free survival. IL-17 and IL-22 were associated with more severe disease. In contrast, higher levels of IL-2 and IL-4 corresponded with higher subsequent LVEF. Increased production of TH17 type cytokines in PPCM correlated with worse disease and outcomes, while an increased immune-regulatory response seems to be protective.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 02 Jul 2021; epub ahead of print
Koczo A, Marino A, Rocco J, Ewald G, ... McNamara DM, IPAC Investigators
Int J Cardiol: 02 Jul 2021; epub ahead of print | PMID: 34224767
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Abstract

Cardiac involvement in consecutive unselected hospitalized COVID-19 population: In-hospital evaluation and one-year follow-up.

Maestrini V, Birtolo LI, Francone M, Galardo G, ... Mancone M, Policlinico Umberto I COVID-19 Group
Background
Cardiovascular disease (CVD) can occur in COVID-19 and has impact on clinical course. Data on CVD prevalence in hospitalized COVID-19 patients and sequelae in survivors is limited. Aim of this prospective study carried out on consecutive unselected COVID-19 population, was to assess: 1) CVD occurrence among hospitalized COVID-19 patients, 2) persistence or new onset of CVD at one-month and one-year follow-up.
Methods
Over 30 days n = 152 COVID-19 patients underwent cardiovascular evaluation. Standard electrocardiogram (ECG), Troponin and echocardiography were integrated by further tests when indicated. Medical history, arterial blood gas, blood tests, chest computed tomography and treatment were recorded. CVD was defined as the occurrence of a new condition during the hospitalization for COVID-19. Survivors attended a one-month follow-up visit and a one-year telephone follow-up.
Results
Forty-two patients (28%) experienced a wide spectrum of CVD with acute myocarditis being the most frequent. Death occurred in 32 patients (21%) and more frequently in patients who developed CVD (p = 0.032). After adjustment for confounders, CVD was independently associated with death occurrence. At one-month follow-up visit, 7 patients (9%) presented persistent or delayed CVD. At one-year telephone follow-up, 57 patients (48%) reported persistent symptoms.
Conclusion
Cardiovascular evaluation in COVID-19 patients is crucial since the occurrence of CVD in hospitalized COVID-19 patients is common (28%), requires specific treatment and increases the risk of in-hospital mortality. Persistence or delayed presentation of CVD at 1-month (9%) and persistent symptoms at 1-year follow-up (48%) suggest the need for monitoring COVID-19 survivors.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 02 Jul 2021; epub ahead of print
Maestrini V, Birtolo LI, Francone M, Galardo G, ... Mancone M, Policlinico Umberto I COVID-19 Group
Int J Cardiol: 02 Jul 2021; epub ahead of print | PMID: 34224766
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Impact:
Abstract

Reduction of arteriovenous access blood flow leads to biventricular unloading in haemodialysis patients.

Valerianova A, Malik J, Janeckova J, Kovarova L, ... Hruskova Z, Tesar V
Aims
Patients on chronic haemodialysis have a wide range of changes in cardiac function and structure, including left ventricular hypertrophy, dilation and diastolic dysfunction or pulmonary hypertension. All these changes were linked to increased mortality in previous studies. High-flow arteriovenous fistulas (AVF) are supposed to be a factor contributing to their development. This study investigated the early effect of surgical AVF blood flow (Qa) reduction on these changes in patients with or without heart failure changes.
Methods and results
Forty-two patients in chronic haemodialysis programme with high-flow AVF (Qa over 1500 mL/min), indicated for surgery for ≥1 of the following indications: 1.manifest heart failure; 2.hand ischemia; 3.advanced structural heart changes detected by echocardiography. The patients underwent echocardiography on selection visit, before blood flow reducing surgery and six weeks thereafter. The Qa reduction led to decrease of left ventricular mass (p = 0.02), end-diastolic volume (p = 0.008), end-diastolic diameter (p = 0.003) and left atrial volume (p = 0.0006). Diastolic function improved. Similarly, right ventricular diameter and right atrial volume decreased (p = 0.000001 and 0.00009, respectively) together with the decrease of estimated pulmonary artery systolic pressure. 81% of patients suffered from pulmonary hypertension prior to surgery, only 36% thereafter.
Conclusion
The surgical restriction of the hyperkinetic circulation leads to several improvements of heart structure and function, which was linked to higher mortality in other studies. The beneficial effect of Qa reduction is present even in patients without symptoms of heart failure. The contribution of AVF must be considered with structural or functional heart changes.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Jun 2021; 334:148-153
Valerianova A, Malik J, Janeckova J, Kovarova L, ... Hruskova Z, Tesar V
Int J Cardiol: 30 Jun 2021; 334:148-153 | PMID: 33895210
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Abstract

Risk stratification in patients with residual pulmonary hypertension after pulmonary endarterectomy.

Ghio S, Klersy C, Corsico A, Gamba SL, ... Visconti LO, D\'Armini AM
Background
Few studies addressed the issue of risk stratification in patients with residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). This study tested the potential added value of parameters that have not been included in existing risk models.
Methods
We evaluated 546 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent PEA and were followed-up for a median period of 58 months.
Results
Among the 242 with residual PH, 27 died and had 127 a clinical worsening event. At univariable analysis, the parameters associated with poor survival were pulmonary vascular resistance (PVR) ≥425 dyn·s·cm-5 (p ≤ 0.001), mean pulmonary artery pressure (mPAP) ≥38 mmHg (p = 0.003) and pulmonary artery compliance (CPA) ≤1.8 ml/mmHg (p = 0.014). In the bivariable models including either PVR or mPAP as first parameter, the addition of CPA was not statistically significant. The parameters associated with poor clinical worsening were CPA ≤1.8 ml/mmHg (p < 0.001), PVR ≥425 dyn·s·cm-5 (p = 0.002), arterial oxygen tension (PaO2) ≤ 75 mmHg (p = 0.003), mPAP ≥38 mmHg (p = 0.008). In a multivariable analysis which included PVR ≥425 as the first parameter, the addition of both CPA ≤1.8 ml/mmHg and of PaO2 ≤ 75 mmHg significantly improved prognostic stratification (Harrel\'s C of the model = 0.64, p < 0.001). Noticeably, the lower tertile of the model\'s predictor index identified a subgroup of 91 patients who had an event rate numerically similar to that of patients without residual PH.
Conclusions
Risk stratification in residual PH can be refined if CPA and PaO2 are considered in association with standard hemodynamic parameters.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Jun 2021; 334:116-122
Ghio S, Klersy C, Corsico A, Gamba SL, ... Visconti LO, D'Armini AM
Int J Cardiol: 30 Jun 2021; 334:116-122 | PMID: 33823214
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Impact:
Abstract

Assessment of cardiac arrhythmias using long-term continuous monitoring in patients with pulmonary hypertension.

Andersen MØ, Diederichsen SZ, Svendsen JH, Carlsen J
Background
Cardiac arrhythmias are considered a prominent phenomenon in patients with pulmonary hypertension (PH). Older studies reported that 8% to 35% of patients with PH had supraventricular tachycardia (SVT), associated with adverse outcomes. Still, these arrhythmias have only been investigated via short-term monitoring or limited electrocardiogram recordings.
Methods
Patients without previous arrhythmias diagnosed with PH at a tertiary facility received an insertable cardiac monitor as part of a prospective cohort study. Baseline assessments included World Health Organization functional class, six-minute walk test, echocardiography, and cardiac magnetic resonance imaging.
Results
Thirty-four patients with PH were included. Twenty-four patients had pulmonary arterial hypertension (PAH) and 10 had chronic thromboembolic PH (CTEPH). During 46 patient-years of continuous monitoring (median: 594 (range: 334-654) days per patient), 70 arrhythmia episodes were recorded in 13 patients (38%), with a median of two (range: 1-3) episodes and an arrhythmic burden median of 1.6 (range: 0.1-228) minutes per patient. SVTs were the most common arrhythmias, with 16% of episodes being atrial fibrillation and 84% being other types of SVTs. Additionally, three patients experienced bradycardias, including one resulting in syncope and subsequent pacemaker implantation. None of the patients had sustained ventricular arrhythmias.
Conclusions
Arrhythmias were seen in 38% of contemporary patients with PH during long-term continuous monitoring; however, the vast majority of episodes were short and self-limiting. Modern therapy may alleviate the development of arrhythmias in stable patients with PH. This study is the first study to deploy long-term continuous monitoring in patients with PH.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Jun 2021; 334:110-115
Andersen MØ, Diederichsen SZ, Svendsen JH, Carlsen J
Int J Cardiol: 30 Jun 2021; 334:110-115 | PMID: 33819493
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Impact:
Abstract

Heart failure outcomes in Aboriginal and Torres Strait Islander peoples in the Hunter New England region of New South Wales.

McGee M, Sugito S, Al-Omary MS, Hartnett D, ... Sverdlov AL, Boyle AJ

Background:
Aboriginal and Torres Strait Islander suffer poor health outcomes, driven predominately by cardiovascular disease. Previous work has focused on remote communities although majority of Aboriginal and Torres Strait Islander patients live in urban New South Wales. We describe the heart failure characteristics and outcomes of the Aboriginal and Torres Strait Islander patients in Hunter New England Health, New South Wales, Australia. Methods A large retrospective, multi-centre cohort study from 2007 till 2016 in a geographically diverse Local Health District. The primary outcomes were all-cause mortality and all-cause readmission. The Aboriginal and Torres Strait Islander cohort was described by demographics, locality, and outcomes relative to the non-Indigenous patients from the same time period. Findings During the study period there were 20,480 index admissions, of which 3.1% identified as Aboriginal and/or Torres Strait Islander. Aboriginal and Torres Strait Islander people admitted were younger by an average of 15 years (81 vs 66 years, p < 0.001), were more likely to live in a non-metropolitan locality (80 vs 61%, p < 0.001). Once adjustments were made for age, there was no significant difference in all-cause mortality. Indigenous status was a strong predictor of readmission on multivariate analysis, hazard ratio of 1.31 (p < 0.001). Interpretation Aboriginal and Torres Strait Islander patients, compared to non-Indigenous patients, who are admitted with heart failure are younger, more commonly live in rural localities and suffer from a higher burden of comorbidities. Once adjustments are made for age and co-morbidities, indigenous status does not portend a worse outcome.


Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Jun 2021; 334:65-71
McGee M, Sugito S, Al-Omary MS, Hartnett D, ... Sverdlov AL, Boyle AJ
Int J Cardiol: 30 Jun 2021; 334:65-71 | PMID: 33839176
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Impact:
Abstract

Efficacy and safety of balloon pulmonary angioplasty for residual pulmonary hypertension after pulmonary endarterectomy.

Ito R, Yamashita J, Sasaki Y, Ikeda S, ... Ogino H, Chikamori T
Background
Pulmonary endarterectomy (PEA) is the standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH), although some patients may experience residual pulmonary hypertension (PH). It is unclear whether balloon pulmonary angioplasty (BPA) is effective for residual PH after PEA. This study aimed to compare the BPA outcomes between patients with residual PH after PEA and those with inoperable CTEPH.
Methods
This retrospective study compared BPA for residual PH after PEA (25 patients, 101 BPA sessions) and BPA alone for inoperable CTEPH (21 patients, 89 BPA sessions). All patients underwent right heart catheterisation and functional and laboratory tests before PEA or before and after BPA.
Results
There was no difference in the number of BPA sessions per patient (4.0 ± 1.9 vs. 4.2 ± 1.9, p = 0.671). No significant differences were observed with respect to the mean pulmonary artery pressure (23.6 ± 9.1 vs. 21.9 ± 5.7 mmHg, p = 0.44), pulmonary vascular resistance (3.7 ± 0.5 vs. 2.8 ± 1.2 Wood units, p = 0.14), 6-min walking distance (392.1 ± 117.7 vs. 452.4 ± 90.1 m, p = 0.096), and World Health Organization functional class (I/II/III/IV: 14/11/0/0 vs. 9/12/0/0, p = 0.375). Severe haemoptysis requiring embolisation was more common in the PH after PEA group (16.0% vs. 5.4%, p = 0.018). However, no patients required mechanical ventilation or extracorporeal membrane oxygenation, and there were no procedural deaths.
Conclusion
Although BPA might be effective for residual PH after PEA, it was associated with a high rate of haemoptysis.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Jun 2021; 334:105-109
Ito R, Yamashita J, Sasaki Y, Ikeda S, ... Ogino H, Chikamori T
Int J Cardiol: 30 Jun 2021; 334:105-109 | PMID: 33839175
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Impact:
Abstract

Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome: A pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients.

Claassens DMF, Gimbel ME, Bergmeijer TO, Vos GJA, ... Deneer VHM, Ten Berg JM
Background
Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y12 inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically.
Methods
Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding).
Results
A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77-1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66-1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62-1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively.
Conclusion
In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and patients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in patients using clopidogrel.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Jun 2021; 334:10-17
Claassens DMF, Gimbel ME, Bergmeijer TO, Vos GJA, ... Deneer VHM, Ten Berg JM
Int J Cardiol: 30 Jun 2021; 334:10-17 | PMID: 33887342
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Impact:
Abstract

Dobutamine stress cardiac MRI is safe and feasible in pediatric patients with anomalous aortic origin of a coronary artery (AAOCA).

Doan TT, Molossi S, Sachdeva S, Wilkinson JC, ... Masand P, Noel CV
Background
Risk stratification in anomalous aortic origin of a coronary artery (AAOCA) is challenged by the lack of a reliable method to detect myocardial ischemia. We prospectively studied the safety and feasibility of Dobutamine stress-cardiac magnetic resonance (DSCMR), a test with excellent performance in adults, in pediatric patients with AAOCA.
Methods
Consecutive DSCMR from 06/2014-12/2019 in patients≤20 years old with AAOCA were included. Hemodynamic response and major/minor events were recorded. Image quality and spatial/temporal resolution were evaluated. Rest and stress first-pass perfusion and wall motion abnormalities (WMA) were assessed. Inter-observer agreement was assessed using kappa coefficient.
Results
A total of 224 DSCMR were performed in 182 patients with AAOCA at a median age of 14 years (IQR 12, 16) and median weight of 58.0 kg (IQR 43.3, 73.0). Examinations were completed in 221/224 (98.9%), all studies were diagnostic. Heart rate and blood pressure increased significantly from baseline (p < 0.001). No patient had major events and 28 (12.5%) had minor events. Inducible hypoperfusion was noted in 31/221 (14%), associated with WMA in 13/31 (42%). Inter-observer agreement for inducible hypoperfusion was very good (Κ = 0.87). Asymptomatic patients with inducible hypoperfusion are considered high-risk and those with a negative test are of standard risk.
Conclusions
DSCMR is feasible in pediatric patients with AAOCA to assess for inducible hypoperfusion and WMA. It can be performed safely with low incidence of major/minor events. Thus, DSCMR is potentially a valuable test for detection of myocardial ischemia and helpful in the management of this patient population.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Jun 2021; 334:42-48
Doan TT, Molossi S, Sachdeva S, Wilkinson JC, ... Masand P, Noel CV
Int J Cardiol: 30 Jun 2021; 334:42-48 | PMID: 33892043
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Impact:
Abstract

Scheduled versus alert transmissions for remote follow-up of cardiac implantable electronic devices: Clinical relevance and resource consumption.

Maines M, Tomasi G, Moggio P, Poian L, ... Valsecchi S, Del Greco M
Background
The remote follow-up of pacemakers and implantable cardiac defibrillators (ICDs) usually includes scheduled checks and alert transmissions. However, this results in a high volume of remote data reviews to be managed. We measured the relative contribution of scheduled and alert transmissions to the detection of relevant conditions, and the workload generated by their management.
Methods
At our center, the frequency of remote scheduled transmissions is 4/year. Moreover, all system-integrity and clinical alerts are turned on for wireless notification. We calculated the number of transmissions received from January to December 2020, and identified transmissions that necessitated in-hospital access for further assessment and transmissions that required clinical discussion with the physician. For all alert transmissions, we identified whether the alert was clinically meaningful (i.e. center was not previously aware of the condition and no action had yet been taken to treat it).
Results
Of 8545 transmissions received from 1697 pacemakers and ICDs, 5766 (67%) were scheduled and 2779 (33%) were alert transmissions received from 764 patients (45%); 499 (9%) scheduled transmissions required clinical discussion with the physician, but only 2 of these necessitated in-hospital visits for further assessment. Of the alert transmissions, 664 (24%) required clinical discussion, and 75 (3%) necessitated in-hospital visits. The proportion of alerts judged clinically meaningful was 7%.
Conclusion
Scheduled transmissions generate 67% of remote data reviews for pacemakers and ICDs, but their ability to detect clinically relevant events is very low. A strategy that relies exclusively on alert transmissions could ensure continuity of patient monitoring while reducing the workload at the center.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Jun 2021; 334:49-54
Maines M, Tomasi G, Moggio P, Poian L, ... Valsecchi S, Del Greco M
Int J Cardiol: 30 Jun 2021; 334:49-54 | PMID: 33930512
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Impact:
Abstract

Prevalence and disease features of myocardial ischemia with non-obstructive coronary arteries: Insights from a dynamic CT myocardial perfusion imaging study.

Xu Y, Yu L, Shen C, Lu Z, Zhu X, Zhang J
Background
Ischemia with non-obstructive coronary arteries (INOCA) is not uncommon in clinical practice. However, the incidence and imaging characteristics of INOCA on dynamic CT myocardial perfusion imaging (CT-MPI) remains unclear. We aimed to investigate the prevalence and disease features of INOCA as evaluated by dynamic CT-MPI + coronary CT angiography (CCTA).
Methods
Patients with suspected chronic coronary syndrome and intermediate-to-high pre-test probability of obstructive CAD (according to updated Diamond and Forrester Chest Pain Prediction Rule) were referred for dynamic CT-MPI + CCTA and retrospectively included. Various parameters, including myocardial blood flow (MBF) and high-risk plaque (HRP) features, were measured. INOCA was diagnosed if patients were revealed to have myocardial ischemia and absence of obstructive stenosis.
Results
314 patients were finally included. 20 patients (6.4%) were observed to have myocardial ischemia without obstructive stenosis. In addition, 138 patients (43.9%) had normal or near normal findings, 101 patients (32.2%) had obstructive stenosis without myocardial ischemia and 55 patients (17.5%) had obstructive stenosis with myocardial ischemia. Compared with patients with normal/near normal findings, patients with INOCA showed a higher prevalence of positive remodeling (40.0% vs. 17.4%, p = 0.04). In patients with obstructive stenosis, the mean age, calcium score and incidence of spotty calcification, positive remodeling as well as HRPs were significantly higher than those in patients with INOCA (p < 0.05 for all).
Conclusions
The overall prevalence of INOCA was low in patients with suspected chronic coronary syndrome. HRPs were less frequently presented in patients with INOCA, compared with patients having obstructive coronary stenosis.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Jun 2021; 334:142-147
Xu Y, Yu L, Shen C, Lu Z, Zhu X, Zhang J
Int J Cardiol: 30 Jun 2021; 334:142-147 | PMID: 33932431
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Impact:
Abstract

Apparent treatment resistant hypertension and the risk of recurrent cardiovascular events and mortality in patients with established vascular disease.

Groenland EH, Bots ML, Asselbergs FW, de Borst GJ, ... Spiering W, UCC-SMART Study Group
Aim
To quantify the relation between apparent treatment resistant hypertension (aTRH) and the risk of recurrent major adverse cardiovascular events (MACE including stroke, myocardial infarction and vascular death) and mortality in patients with stable vascular disease.
Methods
7455 hypertensive patients with symptomatic vascular disease were included from the ongoing UCC-SMART cohort between 1996 and 2019. aTRH was defined as an office blood pressure ≥140/90 mmHg despite treatment with ≥3 antihypertensive drugs including a diuretic. Cox proportional hazard models were used to quantify the relation between aTRH and the risk of recurrent MACE and all-cause mortality. In addition, survival for patients with aTRH was assessed, taking competing risk of non-vascular mortality into account.
Results
A total of 1557 MACE and 1882 deaths occurred during a median follow-up of 9.0 years (interquartile range 4.8-13.1 years). Compared to patients with non-aTRH, the 614 patients (8%) with aTRH were at increased risk of cardiovascular mortality (HR 1.27; 95% CI 1.03-1.56) and death from any cause (HR 1.25; 95% CI 1.07-1.45) but not recurrent MACE (HR 1.13; 95% CI 0.95-1.34). At the age of 50 years, patients with aTRH after a first cardiovascular event on average had a 6.4 year shorter median life expectancy free of recurrent MACE than patients with non-aTRH.
Conclusion
In hypertensive patients with clinically manifest vascular disease, aTRH is related to a higher risk of vascular death and death from any cause. Moreover, patients with aTRH after a first cardiovascular event have a 6.4 year shorter median life expectancy free of recurrent cardiovascular disease.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Jun 2021; 334:135-141
Groenland EH, Bots ML, Asselbergs FW, de Borst GJ, ... Spiering W, UCC-SMART Study Group
Int J Cardiol: 30 Jun 2021; 334:135-141 | PMID: 33932429
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Impact:
Abstract

Detection of atrial fibrillation in asymptomatic at-risk individuals.

Langer A, Healey JS, Quinn FR, Honos G, ... Godin R, AWARE AF Program
Background
Undiagnosed atrial fibrillation (AF) exposes unsuspecting patients to elevated stroke risks. The optimal algorithm for identifying patients who should be screened for AF remains undetermined. The objective of this study is to determine the AF burden in an asymptomatic, at-risk population. We also sought to investigate potential predictors of undiagnosed AF.
Methods
This registry is a prospective observational study assessing continuous ECG monitoring in screening for AF using a wearable single lead 7-day continuous monitoring device. Patients included were asymptomatic individuals, at risk for AF as determined by either 1) ≥65 years of age with ≥1 high risk factor or; 2) ≥75 years of age and ≥2 moderate risk factors. A multivariable logistic regression was used to explore the predictive value of certain patient characteristics in identifying patients susceptible to have undiagnosed AF.
Results
Among the 942 patients included, 25 patients (2.7%) had evidence of AF detected. Only 8 patients had AF duration ≥24 h. History of perioperative AF (OR: 3.25, 95%CI: 1.08-9.79, p = 0.036), age over 85 (OR: 4.71, 95%CI: 1.31-16.92, p = 0.017) and absence of cardiovascular disease (CVD) (OR: 0.27, 95%CI: 0.10-0.76, p = 0.013) were found to be predictive of undiagnosed AF.
Conclusion
This study demonstrates the feasibility of office-based AF screening in at-risk population. The low rate of AF detection suggests that the optimal algorithm for identifying asymptomatic patients who would benefit from continuous screening remains unclear. Advanced age, history of perioperative AF and absence of CVD are variables that could be explored further.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Jun 2021; 334:55-57
Langer A, Healey JS, Quinn FR, Honos G, ... Godin R, AWARE AF Program
Int J Cardiol: 30 Jun 2021; 334:55-57 | PMID: 33932428
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Impact:
Abstract

Strain evaluation for mitral annular disjunction by echocardiography and magnetic resonance imaging: A case-control study.

Wang TKM, Kwon DH, Abou-Hassan O, Chetrit M, ... Griffin BP, Ayoub C
Background
Mitral annular disjunction (MAD) is an increasingly recognized entity associated with mitral valve prolapse (MVP), ventricular arrhythmias and death. Few studies have investigated the utility of myocardial deformation analysis in MAD. We compared chamber quantification including strain by transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) between MVP patients with and without MAD.
Methods
Forty-two patients with MVP (21 with MAD, 21 without MAD) and 21 controls were studied. Global, basal and basal inferolateral (BIL) segmental strains were measured and compared using velocity-vector imaging TTE and feature-tracking CMR.
Results
Mean age was 54 ± 17 years, 19 (46%) were female, and 19 (46%) underwent surgical mitral valve repair with no deaths during follow-up in the 2 groups with MVP. Patients with MAD and MVP had lower basal longitudinal strain by TTE than those with MVP without MAD. Those with MAD and MVP had lower magnitude in BIL and basal segments by circumferential and radial strain by CMR compared to those with MVP without MAD and controls. Amongst global strain parameters, CMR-derived global circumferential strain was independently associated with MAD diagnosis odds ratio 1.49 (per 1%), 95% confidence interval 1.09-2.05, P = 0.014, with optimal threshold of -18.0% having 76% sensitivity and specificity for MAD.
Conclusion
Abnormal circumferential and radial strain patterns in the basal segments by CMR may be useful for identifying regional LV dysfunction associated with MAD.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Jun 2021; 334:154-156
Wang TKM, Kwon DH, Abou-Hassan O, Chetrit M, ... Griffin BP, Ayoub C
Int J Cardiol: 30 Jun 2021; 334:154-156 | PMID: 33932426
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Impact:
Abstract

Sex-specific temporal evolution of circulating biomarkers in patients with chronic heart failure with reduced ejection fraction.

Schreuder MM, Schuurman A, Akkerhuis KM, Constantinescu AA, ... Roeters van Lennep JE, Kardys I
Background
We aimed to assess differences in clinical characteristics, prognosis, and the temporal evolution of circulating biomarkers in male and female patients with HFrEF.
Methods
We included 250 patients (66 women) with chronic heart failure (CHF) between 2011 and 2013 and performed trimonthly blood sampling during a median follow-up of 2.2 years [median (IQR) of 8 (5-10) urine and 9 (5-10) plasma samples per patient]. After completion of follow-up we measured 8 biomarkers. The primary endpoint (PE) was the composite of cardiac death, cardiac transplantation, left ventricular assist device implantation, and hospitalization due to acute or worsened CHF. Joint models were used to determine whether there were differences in the temporal patterns of the biomarkers between men and women as the PE approached.
Results
A total of 66 patients reached the PE of which 52 (78.8%) were male and 14 (21.2%) were female. The temporal patterns of all studied biomarkers were associated with the PE, and overall showed disadvantageous changes as the PE approached. For NT-proBNP, HsTnT, and CRP, women showed higher levels over the entire follow-up duration and concomitant numerically higher hazard ratios [NT-proBNP: women: HR(95%CI) 7.57 (3.17-21.93), men: HR(95%CI) 3.14 (2.09-4.79), p for interaction = 0.104, HsTnT: women: HR(95%CI) 6.38 (2.18-22.46), men: HR(95%CI) 4.91 (2.58-9.39), p for interaction = 0.704, CRP: women: HR(95%CI) 7.48 (3.43-19.53), men: HR(95%CI) 3.29 [2.27-5.44], p for interaction = 0.106). In contrast, temporal patterns of glomerular and tubular renal markers showed similar associations with the PE in men and women.
Conclusion
Although interaction terms are not statistically significant, the associations of temporal patterns of NT-proBNP, HsTnT, and CRP appear more outspoken in women than in men with HFrEF, whereas associations seem similar for temporal patterns of creatinine, eGFR, Cystatin C, KIM-1 and NAG. Larger studies are needed to confirm these potential sex differences.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Jun 2021; 334:126-134
Schreuder MM, Schuurman A, Akkerhuis KM, Constantinescu AA, ... Roeters van Lennep JE, Kardys I
Int J Cardiol: 30 Jun 2021; 334:126-134 | PMID: 33940096
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Impact:
Abstract

Mismatch between morphological and functional assessment of the length of coronary artery disease.

Lodi Rizzini M, Nagumo S, Gallo D, Sonck J, ... Chiastra C, Collet C
Background
Morphological evaluation of coronary lesion length is a paramount step during invasive assessment of coronary artery disease. Likewise, the extent of epicardial pressure losses can be measured using longitudinal vessel interrogation with fractional flow reserve (FFR) pullbacks. We aimed to quantify the mismatch in lesion length between morphological (based on quantitative coronary angiography, QCA, and optical coherence tomography, OCT) and functional evaluations.
Methods
This is a prospective and multicenter study of patients evaluated by QCA, OCT and motorized fractional flow reserve pullbacks (mFFR). The difference in lesion length between the functional and anatomical evaluations was referred to as FAM.
Results
117 patients (131 vessels) were included. Median lesion length derived from angiography was 16.05 mm [11.40-22.05], from OCT was 28.00 mm [16.63-38.00] and from mFFR 67.12 mm [25.38-91.37]. There was no correlation between QCA and mFFR lesion length (r = 0.124, 95% CI -0.168-0.396, p = 0.390). OCT lesion length did correlate with mFFR (r = 0.469, 95% CI 0.156-0.696, p = 0.004). FAM was strongly associated with the improvement in vessel conductance with percutaneous coronary intervention (PCI), higher mismatch was associated with lower post-PCI FFR.
Conclusions
Lesion length assessment differs between morphological and functional evaluations. The morphological-functional mismatch in lesion length is frequent, and influences the results of PCI in terms of post-PCI FFR. Integration of the extent of pressure losses provides clinically relevant information that may be useful for clinical decision-making concerning revascularization strategy.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Jun 2021; 334:1-9
Lodi Rizzini M, Nagumo S, Gallo D, Sonck J, ... Chiastra C, Collet C
Int J Cardiol: 30 Jun 2021; 334:1-9 | PMID: 33933514
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Impact:
Abstract

Antiarrhythmic therapy and risk of cumulative ventricular arrhythmias in arrhythmogenic right ventricle cardiomyopathy.

Cappelletto C, Gregorio C, Barbati G, Romani S, ... Stolfo D, Sinagra G
Objectives
The aim of our study was to investigate the benefit of antiarrhythmic drugs (AAD) - beta-blockers, sotalol or amiodarone - in a cohort of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) patients with long-term longitudinal follow up.
Background
AAD are prescribed in ARVC to prevent ventricular arrhythmias and control symptoms. However, there are no controlled clinical trials and knowledges regarding the efficacy of AAD in ARVC are limited.
Methods
The study population included 123 patients with definite diagnosis of ARVC and ≥ 2 clinical evaluations. The primary outcome was a composite of sudden cardiac death (SCD)/recurrent major ventricular arrythmias (MVA): sudden cardiac arrest, sustained ventricular tachycardia (VT) and appropriate implantable cardioverter defibrillator interventions, including recurrent events in patients with >1 MVA. Time to first event (SCD or MVA) was considered as secondary composite endpoint.
Results
Sixteen patients were taking AAD at baseline and 75 started at least one AAD during a median follow-up of 132 months [61-255]. A total of 37 patients experienced ≥1 MVA with a total count of 83 recurrent MVA. After adoption of a propensity score analysis, no AAD were associated with lower risk of recurrent MVA. However, if dosage of AAD was considered, beta-blockers at >50% target dose were associated with a significant reduction in the risk of MVA compared to patients not taking beta-blockers (HR 0.10, 95% CI 0.02-0.46, p = 0.004).
Conclusions
In a large cohort of ARVC patients with a long-term follow-up, only beta-blockers administrated at >50% target dose were associated with lower risk of SCD/recurrent MVA.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Jun 2021; 334:58-64
Cappelletto C, Gregorio C, Barbati G, Romani S, ... Stolfo D, Sinagra G
Int J Cardiol: 30 Jun 2021; 334:58-64 | PMID: 33961942
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Impact:
Abstract

Prognostic relevance of exercise testing in hypertrophic cardiomyopathy. A systematic review.

Rodrigues T, Raposo SC, Brito D, Lopes LR
Background
Cardiopulmonary exercise test (CPET) is indicated as part of the assessment in hypertrophic cardiomyopathy (HCM) patients and stress echocardiography is often used to assess symptoms. However, the role of exercise testing for prognostic stratification in HCM is still not established.
Aims
To systematically review the evidence on the role of exercise testing for prognostic stratification in hypertrophic cardiomyopathy.
Methods
A systematic review was conducted for eligible publications, between 2010 and 2020, that included evaluation of outcomes and prognosis. In these studies, patients underwent exercise echocardiography and/or cardiopulmonary exercise testing, performed according to predefined protocols. Diverse parameters were assessed in order to determine which were relevant for the prognosis. Analyzed outcomes included death from any cause, sudden cardiac death (SCD) and equivalents, cardiovascular death, heart failure requiring hospitalization or progression to New York Heart Association classes III or IV, cardiac transplantation, non-sustained ventricular tachycardia, stroke, myocardial infarction and invasive septal reduction therapy.
Results
Eighteen publications were included, corresponding to a total of 7525 patients. The mean follow-up period varied between 1 and 8 years. The main findings of these studies revealed that the major predictors of outcomes were abnormal heart rate recovery, abnormal blood pressure response exercise induced wall motion abnormalities, lower peak VO2, higher VE/VCO2, and pulmonary hypertension/exercise-induced pulmonary hypertension.
Conclusion
Although most studies concluded that exercise test results are useful to determine prognosis in HCM, further investigation is needed regarding whether it adds independent value to the current risk stratification strategies.

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 29 Jun 2021; epub ahead of print
Rodrigues T, Raposo SC, Brito D, Lopes LR
Int J Cardiol: 29 Jun 2021; epub ahead of print | PMID: 34214502
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Impact:
Abstract

Long-term mortality in patients undergoing lower-limb revascularization with Paclitaxel eluting devices.

Liistro F, Angioli P, Reccia MR, Ducci K, ... Scatena A, Bolognese L
Background
Paclitaxel-eluting devices (PED) reduce restenosis and target lesion revascularization (TLR) in femoropopliteal intervention. Recent data suggest a two-fold increased long-term mortality in patients treated with PED. The aim of our study is to evaluate if endovascular therapy (EVT) with PED increases mortality risk in patients with symptomatic lower limb peripheral artery disease (PAD) compared to non-eluting devices (NED).
Methods
The study is a retrospective, single-center registry on patients undergoing EVT for PAD from January 2009 to June 2018. Propensity score analysis on logistic regression model for independent predictors of long-term mortality was used to match PED and NED patients. Mortality was assessed at 2, 5 and 7 years in the entired matched population and in a sub-group of patients ≤75 years.
Results
During the study period, 1294 patients, 718 NED and 576 PED, met the inclusion/exclusion criteria and entered in the study. Propensity score matching analysis identified 854 matched patients, 414 PED and 440 NED. The population was mainly characterized by diabetic patients with CLI (80%) and high prevalence of CAD (30%), heart failure (15%) and renal insufficiency (20%). Mean follow-up length was 58 ± 34 months, (median 52.5). Mortality was 18% in NED vs 12% in PED patients at two years (p = 0.01), 36% vs 30% at 5 years (p = 0.03) and 41% vs 39% at seven years (p = 0.2) respectively. In patients ≤75 years, mortality at 7-year was 28% in PED vs 36% in NED, p = 0.07.
Conclusion
These results suggest a reduced mortality at 2 and 5 years with PED as compare to NED treatment in a real-world CLI scenario. At 7-year follow-up, the advantage was numerically evident only in patients ≤75 years.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 29 Jun 2021; epub ahead of print
Liistro F, Angioli P, Reccia MR, Ducci K, ... Scatena A, Bolognese L
Int J Cardiol: 29 Jun 2021; epub ahead of print | PMID: 34216710
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Impact:
Abstract

Effects of empagliflozin on CA125 trajectory in patients with chronic congestive heart failure.

de la Espriella R, Miñana G, Santas E, Núñez G, ... Bayés-Genís A, Núñez J
Introduction
We aimed to evaluate the trajectory of two surrogates of fluid overload -antigen carbohydrate 125 (CA125) and amino-terminal pro-brain natriuretic peptide (NT-proBNP)- after the addition of oral empagliflozin to usual care in a cohort of patients with chronic heart failure (CHF) and type 2 diabetes (T2D).
Methods and results
From October 2015 to February 2019, 60 ambulatory patients with CHF and T2D were retrospectively included. The primary endpoint was to assess the longitudinal trajectory of plasma levels of CA125 and NT-proBNP after empagliflozin initiation. Changes in quantitative variables were evaluated using linear mixed regression. Median CA125 and NT-proBNP at baseline were 17 (11-75) U/mL and 1662 (647-4230) pg/mL, respectively. A total of 510 outpatient visits were recorded [median (interquartile range) of visits per patient: 6 (4-11)] during a median of 1.78 years. We found a significant and steady decrease in the log of CA125 after empagliflozin initiation (p < 0.001). Conversely, the log of NT-proBNP predicted trajectory did not significantly change (p = 0.425).
Conclusion
In this cohort of patients with CHF and T2D, empagliflozin initiation was associated with a significant decrease in CA125 levels without modifying the trajectory of NT-proBNP. Considering that CA125 has emerged as a surrogate marker of tissue congestion, we hypothesize that empagliflozin might predominantly promote extravascular decongestion.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 29 Jun 2021; epub ahead of print
de la Espriella R, Miñana G, Santas E, Núñez G, ... Bayés-Genís A, Núñez J
Int J Cardiol: 29 Jun 2021; epub ahead of print | PMID: 34216708
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Impact:
Abstract

The effect of long-term left ventricular assist device support on flow-sensitive plasma microRNA levels.

Dlouha D, Ivak P, Netuka I, Novakova S, ... Hubacek JA, Pitha J
Background
Implantation of current generation left ventricular assist devices (LVADs) in the treatment of end-stage heart failure (HF), not only improves HF symptoms and end-organ perfusion, but also leads to cellular and molecular responses, presumably in response to the continuous flow generated by these devices. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in multiple biological processes, including the pathogenesis of HF. In our study, we examined the influence of long-term LVAD support on changes in flow-sensitive miRNAs in plasma.
Materials and methods
Blood samples from patients with end-stage heart failure (N = 33; age = 55.7 ± 11.6 years) were collected before LVAD implantation and 3, 6, 9, and 12 months after implantation. Plasma levels of the flow-sensitive miRNAs; miR-10a, miR-10b, miR-146a, miR-146b, miR-663a, miR-663b, miR-21, miR-155, and miR-126 were measured using quantitative PCR.
Results
Increasing quantities of miR-126 (P < 0.03) and miR-146a (P < 0.02) was observed at each follow-up visit after LVAD implantation. A positive association between miR-155 and Belcaro score (P < 0.04) and an inverse correlation between miR-126 and endothelial function, measured as the reactive hyperemia index (P < 0.05), was observed.
Conclusions
Our observations suggest that after LVAD implantation, low pulsatile flow up-regulates plasma levels of circulating flow-sensitive miRNAs, contributing to endothelial dysfunction and vascular remodeling.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 28 Jun 2021; epub ahead of print
Dlouha D, Ivak P, Netuka I, Novakova S, ... Hubacek JA, Pitha J
Int J Cardiol: 28 Jun 2021; epub ahead of print | PMID: 34197842
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Impact:
Abstract

Cardiac imaging in ischemic stroke or transient ischemic attack of undetermined cause: Systematic review & meta-analysis.

van der Maten G, Dijkstra S, Meijs MFL, von Birgelen C, van der Palen J, den Hertog HM
Background
Patients with ischemic stroke or transient ischemic attack (TIA) of undetermined cause often undergo cardiac imaging in search of a cardioembolic source. As the choice of the most appropriate imaging approach is controversial and therapeutic implications have changed over time, we aimed to identify in patients with \"cryptogenic stroke or TIA\" the yield of transthoracic or transesophageal echocardiography (TTE or TEE) and cardiac computed tomography (CT).
Methods and results
We performed a systematic review and meta-analysis according to the PRISMA guidelines. Included were studies that assessed consecutive patients with ischemic stroke or TIA of undetermined cause to evaluate the yield of TTE, TEE, or cardiac CT for detecting cardioembolic sources. For each type of cardioembolic source the pooled prevalence was calculated. Only six out of 1458 studies fulfilled the inclusion criteria (1022 patients). One study reported the yield of TTE, four of TEE, and one of both TTE and TEE; no study assessed cardiac CT. Mean patient age ranged from 44.3-71.2 years, 49.2-59.7% were male. TTE detected 43 cardioembolic sources in 316 patients (4 (1.3%) major, 39 (12.3%) minor), and TEE 248 in 937 patients (55 (5.9%) major, 193 (20.6%) minor). The most prevalent major cardioembolic source was left atrial appendage thrombus, yet results were heterogeneous among studies.
Conclusions
TTE and TEE infrequently detect major cardioembolic sources that require a change of therapy. Findings should be interpreted with caution due to the limited number of studies. A large-sized prospective clinical trial is warranted to support evidence-based decision-making.

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 28 Jun 2021; epub ahead of print
van der Maten G, Dijkstra S, Meijs MFL, von Birgelen C, van der Palen J, den Hertog HM
Int J Cardiol: 28 Jun 2021; epub ahead of print | PMID: 34197841
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Impact:
Abstract

Coronary artery calcium on standard chest computed tomography predicts cardiovascular events after liver transplantation.

Zorzi A, Brunetti G, Cardaioli F, D\'Arcangelo F, ... Cillo U, Pontisso P
Aims
Cardiac complications are a leading cause of mortality after orthotopic liver transplantation (LT) and pre-operative risk stratification is challenging. We evaluated whether coronary artery calcium (CAC) score calculated on a standard (non-thin layer, non-ECG gated) chest computed tomography (CT) predicted cardiac outcome after LT.
Methods
We included a consecutive series of LT recipients who underwent pre-operative cardiac evaluation including stress-testing or cardiac catheterization in high-risk patients. Patients with a history of coronary artery disease or coronary revascularization were excluded. The CAC score was calculated from the chest CT routinely performed before LT. CAC values were not available at the time of pre-transplant cardiac evaluation and did not affect LT eligibility. The primary end-point included peri-operative arrhythmic cardiac arrest and sustained ventricular arrhythmias; heart failure, myocardial infarction and cardiac death within 1-year after LT.
Results
The study population consisted of 301 patients (median age 56 years, 76% males). At chest CT, 49% had CAC = 0; 27% had CAC = 1-99, 15% had CAC = 100-399 and 9% CAC > 400. The primary end-point incidence increased from 7% in patients with CAC = 0 to 27% in patients with CAC > 400 (p = 0.007). At multivariable analysis including traditional risk factors, CAC remained an independent predictor of cardiac events (p = 0.01).
Conclusions
CAC score calculated on a standard chest CT stratified the risk of cardiac events in patients who underwent LT after negative pre-transplant cardiac evaluation. These findings suggest that evaluation of CAC from a standard chest CT performed for other reasons can be used as an early cardiac risk stratification tool before LT.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 25 Jun 2021; epub ahead of print
Zorzi A, Brunetti G, Cardaioli F, D'Arcangelo F, ... Cillo U, Pontisso P
Int J Cardiol: 25 Jun 2021; epub ahead of print | PMID: 34181996
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Abstract

Clinical and prognostic values of urinary alpha1-microglobulin as a tubular marker in acute heart failure.

Ishiwata S, Matsue Y, Nakamura Y, Dotare T, ... Kasai T, Minamino T
Background
Although urinary alpha-1-microglobulin has been used as a marker of tubular dysfunction, its clinical and prognostic values in patients with acute heart failure have not been validated.
Methods
We analyzed 623 patients (74 ± 13 years old, 60.0% male) with acute heart failure in whom urinary alpha-1-microglobulin (A1MG) levels were measured as tubular markers at the time of admission. The primary endpoint was all-cause mortality.
Results
The median levels of urinary alpha-1-microglobulin with and without correction for urinary creatinine concentration were 8.80 (interquartile range: 4.20-17.7) mg/dL and 12.9 (5.92-30.7) mg/gCr, respectively. Urinary A1MG levels were significantly correlated with all of beta-2-microglobulin (r = 0.77), N-acetyl-β-D-glucosaminidase (r = 0.51), and estimated glomerular filtration rate (r = -0.42); however, alpha-1-microglobulin was most often predicted using beta-2-microglobulin or N-acetyl-β-D-glucosaminidase. During the 488-day (interquartile range: 185-938 days) follow-up, 141 deaths occurred. Higher A1MG levels were associated with higher mortality even after adjustment for other covariates. Only A1MG, but not beta-2-microglobulin or N-acetyl-β-D-glucosaminidase, yielded incremental prognostic information in addition to the preexisting prognostic factors (net-reclassification improvement: 0.254, P = 0.023; integrated discrimination improvement: 0.015, P = 0.028).
Conclusions
In patients hospitalized due to acute heart failure, urinary alpha-1-microglobulin was a marker of tubular dysfunction. High alpha-1-microglobulin was associated with all-cause mortality independent of glomerular function and was a better predictor of mortality than urinary beta-2-microglobulin.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 25 Jun 2021; epub ahead of print
Ishiwata S, Matsue Y, Nakamura Y, Dotare T, ... Kasai T, Minamino T
Int J Cardiol: 25 Jun 2021; epub ahead of print | PMID: 34181994
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Abstract

Causal effect of sex hormone-binding globulin and testosterone on coronary heart disease: A multivariable and network Mendelian randomization analysis.

Li Y, Si S, Hou L, Yuan T, ... Liu Y, Xue F
Background
Although observational studies have shown an association between sex hormone-binding globulin (SHBG), testosterone (T) and cardiovascular diseases (CVD), controversy remains. In this study, we aim to explore the causal effects of SHBG and T on Coronary heart disease (CHD).
Methods
We used univariable, network and multivariable mendelian randomization (MR) analysis to investigate the causal effect of SHBG and T on CHD. We performed inverse variance weighted (IVW) MR as the primary analysis, with the robustness of this approach further tested by other methods in sensitivity analysis. The SHBG and T were collected from the UK Biobank data, about 180,000 men aged 40 to 69 years. CHD was collected from CARDIoGRAMplusC4D 1000 Genomes-based GWAS, which was a meta-analysis including 48 studies and involving 60,801 CHD cases and 123,504 controls.
Results
Using univariable MR-IVW, the results suggested that a one standard deviation (SD) increase in SHBG, the risk of CHD decreased by approximately 14% (OR (95% CI): 0.86(0.76,0.97)), and that a SD increase in total testosterone (TT), the risk also decreased, approximately 8% (OR (95% CI): 0.92(0.85,0.99)). Multivariable MR showed that both SHBG and TT had no direct causal effect with CHD (a SD increase in SHBG: OR (95% CI):0.75(0.57,1.00), P = 0.053; a SD increase in TT: OR (95% CI): 1.05(0.90,1.22), P = 0.53). In the network MR analysis, the results suggested that TT might act as mediator in the causal pathway from SHBG to CHD and account for 93% of the total effect of SHBG on CHD, and that SHBG might be a mediator in the causal pathway from TT to CHD and account for 67% of the total effect of TT on CHD.
Conclusions
Genetically predicted SHBG and TT were negatively correlated with CHD in both univariable and network MR, which may provide a causal explanation behind the observed conclusion. In addition, TT and SHBG had a bidirectional causal effect. Further work is required to disentangle the downstream effects of SHBG/TT on CHD and the molecular pathways involved, as the simultaneous regulation of SHBG and TT may make it a viable strategy for the prevention or treatment of CHD.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 24 Jun 2021; epub ahead of print
Li Y, Si S, Hou L, Yuan T, ... Liu Y, Xue F
Int J Cardiol: 24 Jun 2021; epub ahead of print | PMID: 34181993
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Abstract

Echocardiographic predictors of new-onset atrial arrhythmias in patients undergoing hematopoietic stem cell transplantation.

Singh N, Singh A, Besser SA, Lang RM, ... Bishop MR, DeCara JM
Background
Atrial arrhythmias following hematopoietic stem cell transplantation (HSCT) have been associated with increased length of stay, need for intensive care, and increased mortality within one-year post-transplant. We sought to identify echocardiographic parameters that may predict the development of new atrial arrhythmias post-HSCT.
Methods
We performed a retrospective chart review of 753 consecutive patients who underwent HSCT at the University of Chicago from January 2015 through December 2019. Patients with baseline echocardiogram within 6 months prior to transplantation were included. Those with prior transplants, history of atrial arrhythmias, or unavailable echocardiographic images were excluded, resulting in 187 patients included for final analysis. Baseline clinical and demographic variables, as well as echocardiographic parameters, were compared between patients who developed new atrial arrhythmias post-HSCT versus those who did not.
Results
Of the 187 patients included for analysis, 25 (13%) developed new atrial arrhythmias, with 13 of these occurring within 30 days of transplantation. Despite no significant difference in left atrial (LA) end-systolic volume between those with and without new arrhythmia following HSCT (OR 1.04; 95% CI 0.91-1.09, p = 0.233), univariable analysis demonstrated that patients who developed atrial arrhythmias had reduced LA function, as reflected by lower LA emptying fraction (OR 0.94; 95% CI 0.91-0.98, p = 0.003) and lower LA reservoir strain (OR 0.95; 95% CI 0.92-0.99, p = 0.009).
Conclusions
Echocardiographic indices of LA function, namely LA emptying fraction and LA reservoir strain, can identify patients at risk for developing new atrial arrhythmias post-HSCT, prior to the development of morphologic changes in the LA.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 22 Jun 2021; epub ahead of print
Singh N, Singh A, Besser SA, Lang RM, ... Bishop MR, DeCara JM
Int J Cardiol: 22 Jun 2021; epub ahead of print | PMID: 34174337
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Abstract

Inflammatory markers in Eisenmenger syndrome and their association with clinical outcomes. A cross-sectional comparative study.

Gonzaga LRA, Gomes WJ, Rocco IS, Matos-Garcia BC, ... Arena R, Guizilini S
Background
Inflammation may be an important factor contributing to the progression of Eisenmenger syndrome (ES). The purpose of the current study was to: characterize the inflammatory profile in ES patients and compare measures to reference values for congenital heart disease and pulmonary arterial hypertension (CHD-PAH); and investigate whether inflammatory markers are associated with other clinical markers in ES.
Methods
Twenty-seven ES patients were prospectively selected and screened for systemic inflammatory markers, including interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α) and IL-10. Clinical data and echocardiographic parameters were obtained, with concomitant analysis of ventricular function. Functional capacity was assessed using the 6-min walk test (6MWT). Renal function and blood homeostasis were evaluated by the level of blood urea nitrogen (BUN), creatinine, and plasma electrolytes.
Results
Patients with ES expressed higher IL-10, IL-1β and TNF-α compared to reference values of patients with CHD-PAH. IL-10 was negatively associated with BUN (r = -0.39,p = 0.07), creatinine (r = -0.35, p = 0.002), sodium (r = -0.45, p = 0.03), and potassium (r = -0.68, p = 0.003). IL-10 was positively associated with bicarbonate (r = 0.45, p = 0.02) and trended toward a positive association with right ventricular fractional area change (RVFAC) (r = 0.35, p = 0.059). IL-1β was negatively associated with potassium (r = -0.5, p = 0.01). TNF-α demonstrated positive association with creatinine (r = 0.4,p = 0.006), BUN (r = 0.63,p = 0.003), sodium (r = 0.44, p = 0.04), potassium (r = 0.41, p = 0.04), and was negatively associated with RVFAC (r = -0.38,p = 0.03) and 6MWT distance (r = -0.54, p = 0.004).
Conclusion
ES patients exhibit a more severe inflammatory profile compared to reference values for CHD-PAH. Furthermore, inflammatory markers are related to renal dysfunction, right ventricular impairment and poorer functional capacity.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 21 Jun 2021; epub ahead of print
Gonzaga LRA, Gomes WJ, Rocco IS, Matos-Garcia BC, ... Arena R, Guizilini S
Int J Cardiol: 21 Jun 2021; epub ahead of print | PMID: 34171450
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Abstract

Vericiguat, organic nitrates, and heart failure in African Americans.

Ilonze OJ, Guglin M
African Americans (AA) have a higher prevalence of heart failure (HF) when compared with White Americans (3% vs 2%), respectively and HF comes on at an earlier age and is more severe in AA. The A-HEFT trial with the combination of hydralazine and isosorbide dinitrate (ISDNHYD) for self-described AA with NYHA class III-IV heart failure with reduced ejection fraction (HFrEF) showed reduction in mortality and HF hospitalizations with a class I level of evidence A recommendation in the ACC/AHA guidelines. Vericiguat is an oral soluble guanylate cyclase stimulator that enhances the cyclic guanosine monophosphate (GMP) pathway. A randomized, double-blind, placebo-controlled trial in patients with higher risk HFrEF in which AA were underrepresented found that vericiguat reduced the composite primary outcome of cardiovascular death or first HF hospitalization. In the new era of guideline directed medical therapies of quadruple therapy - hydralazine and isosorbide dinitrate should be preferred over vericiguat in AA with HFrEF.

Copyright © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 18 Jun 2021; epub ahead of print
Ilonze OJ, Guglin M
Int J Cardiol: 18 Jun 2021; epub ahead of print | PMID: 34157357
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Abstract

Recognition of pre-hypertrophic cardiac involvement in Fabry Disease based on automated electrocardiographic measures.

Namdar M, Richardot P, Johner N, Shah D, ... Olivotto I, Macfarlane P
Background
Various electrocardiographic (ECG) indices have been shown to be useful for early recognition and staging of cardiac involvement in Fabry Disease (FD). However, many of them lack acceptable sensitivity and specificity. We assessed the value of automated ECG measures to discriminate between pre-hypertrophic FD and healthy individuals.
Methods and results
Normal ECGs from 1496 healthy individuals (57.4% male, age 37.4 ± 13 years) were compared to those of 142 FD patients without LVH (37.3% male, age 41.5 ± 18 years). All ECGs were analyzed centrally and a total of 429 automated ECG measures per individual were included for step-wise analysis. The Cramer V statistic was first used to pick out those parameters which were helpful in discriminating between the two groups and a final selection was made by using two models, namely the FLD (Fisher Linear Discrimination) and the Logistic model, to optimise diagnostic performance for the detection of cardiac involvement in FD patients vs. specificity in healthy individuals. The three-step statistical analysis identified 9 ECG parameters as most significant for the discrimination between the groups. The combined discriminant score yielded 64% sensitivity and 97% specificity for correct classification of FD patients in the test sample with a logistic area under curve of the ROC analysis of 0.97.
Conclusion
The combination of automated ECG measures identified via a stepwise statistical approach may be useful for detection of FD patients in the pre-hypertrophic stage. These data are promising for screening purposes in the very early stages of FD cardiomyopathy and warrant prospective confirmation.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 18 Jun 2021; epub ahead of print
Namdar M, Richardot P, Johner N, Shah D, ... Olivotto I, Macfarlane P
Int J Cardiol: 18 Jun 2021; epub ahead of print | PMID: 34157356
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Abstract

Transcatheter mitral valve repair may increase eligibility for heart transplant listing in patients with end-stage heart failure and severe secondary mitral regurgitation.

Doldi PM, Buech J, Orban M, Samson-Himmelstjerna P, ... Hausleiter J, Braun D
Background
Heart transplantation remains the gold standard for treatment of patients with end-stage heart failure and severely reduced ejection fraction (HFrEF). An increased pulmonary vascular resistance (PVR), which is often prevalent in HFrEF patients with secondary mitral regurgitation (SMR), limits the eligibility for transplantation. Therefore, we evaluated whether transcatheter mitral valve repair (TMVr) improves pulmonary circulatory hemodynamics and increases the eligibility for transplantation in end-stage HFrEF patients with severe SMR.
Methods
We retrospectively analysed the hemodynamics by right heart catheterization (RHC) as well as laboratory and clinical outcomes of end-stage HFrEF patients with SMR that underwent TMVr.
Results
Seventeen patients (age: 55 ± 10 yrs) underwent TMVr and repeat RHC at a mean follow-up of 5.7 ± 7.9 months. TMVr decreased PVR (3.5 ± 2.2 to 2.3 ± 1.2 wood units, p = 0.02) and systolic pulmonary artery pressure (55.4 ± 15 mmHg to 45.6 ± 9.8 mmHg, p = 0.02) from baseline to follow-up, respectively, while cardiac output was increased (3.7 ± 0.9 l/min to 4.6 ± 1.3 l/min, p = 0.02). In addition, transpulmonary gradient decreased significantly (12.0 ± 7.5 mmHg to 9.7 ± 5.3 mmHg, p = 0.04). The prevalence of New York Heart Association functional class ≥III at follow-up was reduced from 88% (15/17 patients) to 47% (8/17 patients, p = 0.01). All five patients with initially too high PVR (>3.5 WU) showed a significant decrease in PVR and three of them became potential candidates for heart transplantation after TMVr.
Conclusion
TMVr is associated with reduction in PVR which may increase eligibility for transplantation in some HFrEF patients with severe SMR.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 18 Jun 2021; epub ahead of print
Doldi PM, Buech J, Orban M, Samson-Himmelstjerna P, ... Hausleiter J, Braun D
Int J Cardiol: 18 Jun 2021; epub ahead of print | PMID: 34157353
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Abstract

Advanced deep learning methodology for accurate, real-time segmentation of high-resolution intravascular ultrasound images.

Bajaj R, Huang X, Kilic Y, Ramasamy A, ... Zhang Q, Bourantas CV
Aims
The aim of this study is to develop and validate a deep learning (DL) methodology capable of automated and accurate segmentation of intravascular ultrasound (IVUS) image sequences in real-time.
Methods and results
IVUS segmentation was performed by two experts who manually annotated the external elastic membrane (EEM) and lumen borders in the end-diastolic frames of 197 IVUS sequences portraying the native coronary arteries of 65 patients. The IVUS sequences of 177 randomly-selected vessels were used to train and optimise a novel DL model for the segmentation of IVUS images. Validation of the developed methodology was performed in 20 vessels using the estimations of two expert analysts as the reference standard. The mean difference for the EEM, lumen and plaque area between the DL-methodology and the analysts was ≤0.23mm2 (standard deviation ≤0.85mm2), while the Hausdorff and mean distance differences for the EEM and lumen borders was ≤0.19 mm (standard deviation≤0.17 mm). The agreement between DL and experts was similar to experts\' agreement (Williams Index ranges: 0.754-1.061) with similar results in frames portraying calcific plaques or side branches.
Conclusions
The developed DL-methodology appears accurate and capable of segmenting high-resolution real-world IVUS datasets. These features are expected to facilitate its broad adoption and enhance the applications of IVUS in clinical practice and research.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 17 Jun 2021; epub ahead of print
Bajaj R, Huang X, Kilic Y, Ramasamy A, ... Zhang Q, Bourantas CV
Int J Cardiol: 17 Jun 2021; epub ahead of print | PMID: 34153412
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Abstract

Knocking out c-Jun promotes cardiomyocyte differentiation from embryonic stem cells.

Su L, Zhang G, Zhong H, Luo L, ... Zhu P, Kang K
Background
Morbidity and mortality associated with cardiovascular diseases, such as myocardial infarction, stem from the inability of terminally differentiated cardiomyocytes to regenerate, and thus repair the damaged myocardial tissue structure. The molecular biological mechanisms behind the lack of regenerative capacity for those cardiomyocytes remains to be fully elucidated. Recent studies have shown that c-Jun serves as a cell cycle regulator for somatic cell fates, playing a key role in multiple molecular pathways, including the inhibition of cellular reprogramming, promoting angiogenesis, and aggravation of cardiac hypertrophy, but its role in cardiac development is largely unknown. This study aims to delineate the role of c-Jun in promoting early-stage cardiac differentiation.
Methods
The c-Jun gene in mouse embryonic stem cells (mESCs) was knocked out with CRISPR-Cas9, and the hanging drop method used to prepare the resulting embryoid bodies. Cardiac differentiation was evaluated up to 9 days after c-Jun knockout (ko) via immunofluorescence, flow cytometric, and qPCR analyses.
Results
Compared to the wild-type control group, obvious beating was observed among the c-Jun-ko mESCs after 6 days, which was also associated with significant increases in myocardial marker expression. Additionally, markers associated with mesoderm and endoderm cell layer development, essential for further differentiation of ESCs into cardiomyocytes, were also up-regulated in the c-Jun-ko cell group.
Conclusions
Knocking out c-Jun directs ESCs towards a meso-endodermal cell lineage fate, in turn leading to generation of beating myocardial cells. Thus, c-Jun plays an important role in regulating early cardiac cell development.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 13 Jun 2021; epub ahead of print
Su L, Zhang G, Zhong H, Luo L, ... Zhu P, Kang K
Int J Cardiol: 13 Jun 2021; epub ahead of print | PMID: 34139231
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Abstract

Renin-angiotensin system inhibition and outcome after coronary artery bypass grafting: A population-based study from the SWEDEHEART registry.

Martinsson A, Nielsen SJ, Björklund E, Pivodic A, ... Hansson EC, Jeppsson A
Background
Renin-angiotensin system (RAS) inhibitors are recommended postoperatively to coronary artery bypass grafting (CABG) patients with reduced left ventricular function, diabetes, hypertension or previous myocardial infarction, but not to remaining patients. The aim of the study was to assess the long-term utilization of RAS inhibitors after CABG in patients with and without indication for treatment, and its association with outcome.
Methods
All patients (n = 28,782) not meeting exclusion criterion in Sweden who underwent isolated first time CABG from 2006 to 2015 were included using nationwide registries. The association between treatment and outcome was assessed using adjusted Cox regression models with time-updated data on medications. The primary outcome was major adverse cardiovascular events (MACE), defined as all-cause mortality, stroke and/or myocardial infarction.
Results
At baseline 26,284 (91.3%) of the patients had at least one indication for RAS inhibition while 2498 (8.7%) had not. RAS inhibitors were dispensed to 77.0% and 29.7% of patients with and without indication respectively. Dispense declined over time. RAS inhibition was associated with a reduction in MACE in the whole study population (adjusted hazard ratio (aHR) 0.88, 95% confidence interval (95% CI) 0.83-0.93, p < 0.0001), and in patients with (aHR 0.87 95% CI: 0.82-0.93, p < 0.0001) and without indication (aHR 0.75, 95% CI: 0.58-0.98, p = 0.034).
Conclusions
RAS inhibition is underutilized after CABG. The use of RAS inhibitors was associated with a reduction in MACE, both in patients with and without indication for treatment. The results suggest that RAS inhibition is beneficial for all CABG patients. Randomized controlled trials are necessary to confirm this hypothesis.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 May 2021; 331:40-45
Martinsson A, Nielsen SJ, Björklund E, Pivodic A, ... Hansson EC, Jeppsson A
Int J Cardiol: 14 May 2021; 331:40-45 | PMID: 33359277
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Abstract

The inter-rater reliability and individual reviewer performance of the 2012 world heart federation guidelines for the echocardiographic diagnosis of latent rheumatic heart disease.

Scheel A, Mirabel M, Nunes MCP, Okello E, ... Sable C, Beaton A
Background
In 2012, the World Heart Federation (WHF) published guidelines for the echocardiographic diagnosis of rheumatic heart disease (RHD). This study assesses individual reviewer performance and inter-rater agreement and reliability on the presence of any RHD, as well classification of RHD based on the 2012 WHF criteria.
Methods
Four cardiologists individually reviewed echocardiograms in the context of a randomized clinical trial (ClinicalTrials.gov:NCT03346525) and participated in a blinded adjudication panel. Panel decision was the reference standard for diagnosis. Performance of individual reviewers to panel adjudication was compared through sensitivity and specificity analyses and inter-rater reliability was assessed between individual panelists using Fleiss free marginal multirater kappa.
Results
Echocardiograms from 784 children had two independent reports and panel adjudication. The accuracy of independent reviewers for any RHD had high sensitivity (94%, 95% CI 93-95%) and moderate specificity (62%, 95% CI 53-70%). Sensitivity and specificity for definite RHD was 61.3 (95% CI, 55.3-67.1) and 93.1 (95% CI, 91.6-94.4), with 86.8 (84.7-88.7) and 65.8 (61.0-70.4) for borderline RHD. There was moderate inter-rater agreement (κ = 0.66) on the presence of any RHD while agreement for specific 2012 WHF classification was only fair (κ = 0.51).
Conclusions
The 2012 WHF guidelines are moderately reproducible when used by expert cardiologists. More cases of RHD were diagnosed by an consensus panel than by individual reviewers. A revision to the criteria is now warranted to further increase the reliability of the WHF criteria.

Copyright © 2020 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Apr 2021; 328:146-151
Scheel A, Mirabel M, Nunes MCP, Okello E, ... Sable C, Beaton A
Int J Cardiol: 30 Apr 2021; 328:146-151 | PMID: 33186665
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This program is still in alpha version.