Journal: Int J Cardiol

Sorted by: date / impact
Abstract

Comparison of fluoroscopy and transesophageal echocardiogram for intra-procedure device surveillance assessment during implantation of Watchman.

Zhang X, Jin Q, Kong D, Jiang Y, ... Zhou D, Ge J
Objectives
To evaluate intraprocedural assessments using transesophageal echocardiography (TEE) and fluoroscopy during left atrial appendage occlusion (LAAO) with the WATCHMAN device.
Method
A total of 208 patients with non-valvular atrial fibrillation (AF) undergoing LAAO were included in this study[101 standard procedures (retrospective cohort) and 107 with fluoroscopy-alone approach (prospective cohort). Individual device position, anchoring, compression and peri-device leak (PDL) were successively analyzed based on TEE and fluoroscopy in the retrospective cohort to summarize detailed fluoroscopic assessments for prospective application. Clinical outcomes were assessed between two cohorts.
Results
For retrospective cohort, TEE and fluoroscopy agreed on device position and anchoring. Compression upon fluoroscopy was well correlated with 2D-TEE (r = 0.908) and the difference in overall detection of PDL was not statistically significant between two imaging modalities (p = 0.304). For the prospective cohort with fluoroscopy-guidance alone, implantation success was similar to that of the retrospective cohort (98.13% vs 100%, p = 0.498). The incidence rate of major clinical adverse events was relatively higher in prospective cohort during hospitalization and follow-up but did not reach significant difference (5.61% vs 1.98%; 0.99% vs 0.93%, p > 0.05). Moreover, the prospective group presented with shorter procedural duration, shorter in-hospital stay and lower total hospitalization cost than retrospective group.
Conclusion
LAAO performed by experienced operators in large volume centers is feasible under fluoroscopy guidance. However, there is still a trend in favor of TEE for greater procedural safety and more complete LAA seal. We suggest that this minimalist approach could be proposed in cases with contraindication to general anesthesia and/or TEE.

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

Int J Cardiol: 31 Jan 2021; 324:72-77
Zhang X, Jin Q, Kong D, Jiang Y, ... Zhou D, Ge J
Int J Cardiol: 31 Jan 2021; 324:72-77 | PMID: 32882298
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Abstract

Radio-contrast medium exposure and dialysis risk in patients with chronic kidney disease and congestive heart failure: A case-only study.

Wu MY, Chen TT, Wu MS, Tu YK
Background
Dialysis for end stage renal disease is considered a major public health challenge. Pre-existing chronic kidney disease (CKD) and congestive heart failure (CHF) may be independent risk factors for contrast-induced acute kidney injury. The aim of this study is to investigate dialysis risk in patients with CKD and CHF after radio-contrast medium exposure or coronary catheterization.
Method
This case-crossover design used the Health Insurance Database to identify incident dialysis patients with CKD and CHF. Patients themselves in 6 months ago serve as their own controls. This prevents selection bias in the control group, such as healthy volunteer bias and confounding bias. Conditional logistic regression model was used to estimate the risk of dialysis shortly after radio-contrast medium exposure.
Results
In total, 36,709 patients with CKD and CHF underwent dialysis after radio-contrast medium exposure. At 1 week, the odds ratio (OR) for dialysis was 4.49 (95% Confidence Interval: 3.99-5.05). The ORs for acute-temporary (N = 23,418) and chronic dialysis (N = 13,291) were 5.57 (4.83-6.42) and 2.37 (1.90-2.95) after radio-contrast medium exposure, respectively. The ORs for dialysis after radio-contrast medium exposure in advanced CKD patients (N = 12,030) were 3.25 (2.53-4.19) and 4.85 (4.24-5.54) in early CKD patients (N = 24,679). The ORs for dialysis after coronary catheterization in patients with CKD and CHF was 3.75 (2.57-5.48).
Conclusions
In this study, the clinical risk for acute-temporary or chronic dialysis was significantly high when the bias was fully considered. We need strategies to reduce the subsequent risk of dialysis after radio-contrast medium exposure, especially in patients with CKD and CHF.

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

Int J Cardiol: 31 Jan 2021; 324:199-204
Wu MY, Chen TT, Wu MS, Tu YK
Int J Cardiol: 31 Jan 2021; 324:199-204 | PMID: 32926946
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Abstract

Left atrial strain as a pre-operative prognostic marker for patients with severe mitral regurgitation.

Mandoli GE, Pastore MC, Benfari G, Bisleri G, ... Mondillo S, Cameli M
Background
In patients with severe mitral regurgitation (MR), additional echocardiographic indices could be helpful to optimize surgical timing before irreversible left heart myocardial dysfunction has occurred. We investigated the correlation of left atrial (LA) strain by speckle tracking echocardiography with prognosis after mitral surgery for severe MR, and its association with LA fibrosis.
Method
71 patients with primary severe MR undergoing pre-operative echocardiographic assessment were initially enrolled. Exclusion criteria were: other valvular disease>moderate, history of coronary artery disease, heart failure (HF), hypertrophic cardiomyopathy, left bundle branch block, previous pacemaker implantation, heart transplantation, poor acoustic window. The primary endpoint was the occurrence of composite events (HF and mortality); the secondary endpoint was post-operative functional capacity (NYHA and Borg CR10 class). LA fibrosis was assessed by atrial biopsy specimens in a subset of patients.
Results
Of 65 eligible patients, the primary endpoint occurred in 30 patients (medium follow-up: 3.7 ± 1 years for event-group, 6.8 ± 1 years for non-event group). After Kaplan-Meier analysis, peak atrial longitudinal strain (PALS) provided good risk stratification (5-year event-free survival:90 ± 5% for PALS≥21% vs 30 ± 9% for PALS<21%, p < 0.0001); it was an independent and incremental predictor of outcome in four multivariate Cox adjusted models. There was also an association between PALS and the secondary endpoint (NYHA: r = 0.11, p = 0.04; Borg CR10: r = 0.10, p = 0.02) and an inverse correlation between PALS<21% and LA fibrosis (r 0.80, fibrosis: 76.6 ± 20.7% vs 31.9 ± 20.8%;p < 0.0001).
Conclusions
Global PALS emerged as a reliable predictor of outcome and functional capacity for severe primary MR, and as a marker of LA fibrosis.

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

Int J Cardiol: 31 Jan 2021; 324:139-145
Mandoli GE, Pastore MC, Benfari G, Bisleri G, ... Mondillo S, Cameli M
Int J Cardiol: 31 Jan 2021; 324:139-145 | PMID: 32920069
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Abstract

Recovery of atrial contractile function after cut-and-sew maze for long-standing persistent valvular atrial fibrillation.

Jin Y, Wang HS, Han JS, Zhang J, ... Yu Y, Zhao Y
Objective
The recovery of atrial contractile (AC) after maze has been concerned and even questioned. Now, studied the AC recovery degree and its influencing factors.
Method
237 patients with valvular long-standing persistent atrial fibrillation (AF) were retrospectively grouped according to whether sinus rhythm(SR) maintained and AC restored: SR-AC (163 cases), SR-no-AC (41 cases) and AF-no-AC (33 cases). SR-AC were grouped according to Em/Am ratio. Em/Am≤2 showed that the AC recovered well.
Results
The SR maintained rate (161/177, 90.96%) in patients underwent the cut-and-sew maze III (CSM) was significantly higher than that in cryoablation (43/60, 71.7%). Preoperative AF duration had no significant difference among three groups (P = 0.679). Maze methods had significant relationship with whether SR recovered, P < 0.05, but no significant relationship with whether AC recovered in SR maintained patients (P = 0.280). Nearly 80% (163/204) patients can recover AC, among 156 patients (156/204, 76.5%) recovered contractile of left and right atrium, and 63 (63/204, 30.1%) recovered significant left atrial contractile, that is, Em/Am≤2. Whether AC was significantly restored was not related to maze methods, P = 0.370. AC recovered degree in rheumatic heart disease (RHD) patients was worse than that in mitral valve prolapse (MVP) patients, P = 0.004.
Conclusion
To sum up, the CSM is safe and effective, and the atrial contractile function recovery was found in 80%. The key to the success of maze is to form a complete and lasting electrical isolation, and there was no difference in the rate of atrial contractile recovery when postoperative SR was maintained, no matter what maze method is used. MVP patients should be treated with maze more actively than RHD patients.

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

Int J Cardiol: 31 Jan 2021; 324:84-89
Jin Y, Wang HS, Han JS, Zhang J, ... Yu Y, Zhao Y
Int J Cardiol: 31 Jan 2021; 324:84-89 | PMID: 32920067
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Abstract

Spectrum of cardiac involvement in patients with dengue fever.

Shah C, Vijayaraghavan G, Kartha CC
Background
Dengue fever (DF) is an infectious disease of viral origin common in the tropics. Studies on a large number of patients with dengue infection to assess associated cardiac involvement are rare.
Methods
We analyzed the incidence and spectrum of cardiac abnormalities in 320 patients with dengue fever admitted to our hospital located in an endemic area for dengue infection. All patients were evaluated following the WHO guidelines. Those confirmed to have dengue infection by serology had detailed clinical evaluation, 12‑lead electrocardiography (ECG), assay for cardiac markers (troponin T, CK-MB, NT Pro BNP) and 2-D echocardiography.
Results
Among the 320 patients selected for the study 112 (35%) had changes of cardiac involvement as detected by investigations. Changes in ECG were seen in all of them. Sinus bradycardia in spite of fever was the most common abnormality (n = 63;19.7%). Forty-two (13.1%) patients had left ventricular ejection fraction less than 40%. Forty-eight patients (15%) had increased serum levels of troponin-T. Serum levels of CK-MB were elevated in 34 (10.6%) and serum levels of NT-pro BNP was increased in 19 (5.9%). Fourteen patients died and all of them had abnormalities in electrocardiogram, echocardiogram and serum markers.
Conclusion
Our study reveals that cardiac involvement in patients with dengue infection is not uncommon. We found that ECHO or ECG abnormalities or elevated serum levels of markers of cardiac injury are predictors of risk for adverse outcome. Absence of these abnormalities has a 100% negative predictive value.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 31 Jan 2021; 324:180-185
Shah C, Vijayaraghavan G, Kartha CC
Int J Cardiol: 31 Jan 2021; 324:180-185 | PMID: 32931859
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Abstract

Prevalence and clinical significance of totally occluded infarct-related arteries in patients with non-ST-segment elevation acute coronary syndromes.

Almendro-Delia M, Seoane García T, Villar Calle P, García González N, ... Hidalgo Urbano RJ, García-Rubira JC


Background:
Seemingly conflicting findings exist regarding the prognostic impact of totally occluded infarct-related arteries (oIRA) in non-ST elevation acute coronary syndromes (NSTE-ACS). Methods Retrospective analysis of prospective multicenter registry data comprising a single-center NSTE-ACS cohort, aimed at assessing the impact of occluded (TIMI flow 0/1) versus patent culprit vessels (pIRA, TIMI flow 2/3) on the composite endpoint of all-cause death and cardiogenic shock events at 30 days. Results Of 568 patients, 183 (32.5%) had oIRA. Male sex, refractory angina, ECG suggestive of multivessel or left main disease, and larger infarct sizes with inferior/posterolateral wall involvement, were identified as highly specific markers of oIRA. Successful culprit-lesion revascularization occurred more frequently in patent than in oIRA (90% vs. 96%; P = 0.013). Conversely, patients with oIRA more frequently achieved successful revascularization of concurrent non-IRAs including chronic total occlusions than did those with pIRA (28% vs. 3%; P = 0.0005). Multivariate analysis revealed neutral effects of oIRA on outcomes and identified incomplete revascularization as a powerful predictor of mortality. Moderation analysis revealed a significant interaction between completeness of revascularization and IRA patency, whereby among the incompletely revascularized patients, those with oIRA enjoyed a significant survival advantage over their counterparts with pIRA (11.8% vs. 28%, adjusted OR 0.34; 95% CI 0.10-0.73; P = 0.012).
Conclusions:
Approximately one third of NSTE-ACS patients in this cohort had oIRA. However, compared with pIRA, the occurrence of oIRA did not portend poor outcomes, likely resulting from the higher rate of incomplete revascularization and increased risk of subsequent mortality in patients with pIRA. These exploratory findings warrant further investigation.

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

Int J Cardiol: 31 Jan 2021; 324:1-7
Almendro-Delia M, Seoane García T, Villar Calle P, García González N, ... Hidalgo Urbano RJ, García-Rubira JC
Int J Cardiol: 31 Jan 2021; 324:1-7 | PMID: 32931857
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Abstract

Association of Body Mass Index with Endothelial Function in Asian Men.

Kajikawa M, Maruhashi T, Kishimoto S, Hashimoto H, ... Nakashima A, Higashi Y
Background
The association of body weight with cardiovascular events is still controversial. We evaluated the relationship between body mass index (BMI) and endothelial function.
Methods
We measured flow-mediated vasodilation (FMD) and BMI in 7682 men. All participants were divided into four groups by BMI: underweight (<18.5 kg/m), normal weight (18.5 to 24.9 kg/m), overweight (25.0 to 29.9 kg/m), and obesity (≥30.0 kg/m).
Results
Multiple logistic regression analysis revealed that overweight (OR: 1.30, 95% CI: 1.14-1.47; P < 0.001) and obesity (OR: 1.40, 95% CI: 1.09-1.80; P = 0.009) were associated with an increased risk of a low quartile of FMD. In 5571 younger adults (<60 years), overweight (OR: 1.34, 95% CI: 1.16-1.55; P < 0.001) and obesity (OR: 1.37, 95% CI: 1.04-1.81; P = 0.03) were associated with an increased risk of a low quartile of FMD, and underweight (OR: 0.56, 95% CI: 0.35-0.89; P = 0.01) was associated with a reduced risk of a low quartile of FMD. In 2111 older adults (≥60 years), underweight (OR: 2.16, 95% CI: 1.22-3.80; P = 0.008) was associated with an increased risk of a low quartile of FMD, and overweight and obesity were not associated with a risk of a low quartile of FMD.
Conclusions
In Asian men, endothelial function was impaired in the overweight and obesity groups compared with that in the normal weight group. The risk for endothelial dysfunction was higher in obese younger adults than in obese older adults. The association of BMI with endothelial function may be different in young and elderly men.
Clinical trial registration information
http://www.umin.ac.jp (University Hospital Medical Information Network Clinical Trials Registry) (UMIN000012952).

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

Int J Cardiol: 31 Jan 2021; 324:186-192
Kajikawa M, Maruhashi T, Kishimoto S, Hashimoto H, ... Nakashima A, Higashi Y
Int J Cardiol: 31 Jan 2021; 324:186-192 | PMID: 32931855
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Abstract

\"Concealed cardiomyopathy\" as a cause of previously unexplained sudden cardiac arrest.

Isbister JC, Nowak N, Butters A, Yeates L, ... Bagnall RD, Semsarian C
Background
Genetic heart disease is a common cause of sudden cardiac arrest (SCA) in the young and those without an ischaemic precipitant. Identifying a cause of SCA in these patients allows for targeted care and family screening. Current guidelines recommend limited, phenotype-guided genetic testing in SCA survivors where a specific genetic condition is suspected and genetic testing is not recommended in clinically-idiopathic SCA survivors.
Objective
To investigate the diagnostic utility of broad, multi-phenotype genetic testing in clinically-idiopathic SCA survivors.
Methods
Clinically-idiopathic SCA survivors underwent analysis of genes known to be associated with either cardiomyopathy or primary arrhythmia syndromes, following referral to a specialised genetic heart disease clinic in Sydney, Australia between 1997 and 2019. Comprehensive review of clinical records, investigations and re-appraisal of genetic data according to current variant classification criteria was performed.
Results
In total, 22% (n = 8/36) of clinically-idiopathic SCA survivors (mean age 36.9 ± 16.9 years, 61% male) had a disease-causing variant identified on broad genetic testing. Of these, 7 (88%) variants resided in cardiomyopathy-associated genes (ACTN2, DES, DSP, MYBPC3, MYH7, PKP2) despite structurally normal hearts or sub-diagnostic structural changes at the time of arrest, so-called \"concealed cardiomyopathy\". Only one SCA survivor had a variant identified in a channelopathy associated gene (SCN5A).
Conclusion
Extended molecular analysis with multi-phenotype genetic testing can identify a \"concealed cardiomyopathy\", and increase the diagnosis rate for clinically-idiopathic SCA survivors.

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

Int J Cardiol: 31 Jan 2021; 324:96-101
Isbister JC, Nowak N, Butters A, Yeates L, ... Bagnall RD, Semsarian C
Int J Cardiol: 31 Jan 2021; 324:96-101 | PMID: 32931854
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Abstract

Direct oral anticoagulants in the prevention of stroke in breast cancer patients with atrial fibrillation during adjuvant endocrine therapy: A cohort study.

Pacholczak-Madej R, Bazan-Socha S, Zaręba L, Undas A, Dropiński J
Background
Atrial fibrillation (AF) is a frequent comorbidity in malignant patients. Anticancer therapies complicate anticoagulant strategy. We evaluated the safety and efficacy of long-term use of direct oral anticoagulants (DOACs) in breast cancer women.
Methods
In a prospective cohort study we enrolled 48 consecutive radically treated breast cancer women with AF (median age 63 [interquartile range 56-69] years, CHADS-VASc 2 [2,3]) score) and adjuvant hormonal therapy. Thromboembolic complications (stroke, transient ischemic attack [TIA], venous thromboembolism [VTE]) and bleeding events (major and clinically relevant non-major bleeding [CRNMB]) were recorded in follow-up.
Results
During a median follow-up of 40 (interquartile range 28-50.5) months 13 (27%) patients received apixaban, 22 (46%) rivaroxaban, and 13 (27%) dabigatran. One stroke (2.3%/year) and two CRNMBs (4.6%/year) were observed on apixaban. One TIA (1.3%/year), three major bleedings and two CRNMBs (6.7%/year, combined) were reported on rivaroxaban. Three VTE were documented in dabigatran treated individuals (7.8%/year), without any bleeding or cerebrovascular events. Women with thromboembolic events had higher body mass index (32 [29-33]) vs. 26 [24-29]) kg/m, p = 0.02) and CHADS-VASc score (3 [3]) vs. 2 [1-3]), p = 0.02). Most thromboembolic complications (n = 4, 80%) and all three major bleedings were observed in tamoxifen users, while three of four CRNMBs occurred on aromatase inhibitors. Mortality rates were low (apixaban, n = 1 [2.3%/year], rivaroxaban, n = 3 [5.22%/ year], and dabigatran, n = 2 [4%/ year]). No death was related to bleeding.
Conclusions
This study suggests that DOACs are an effective and safe therapeutic option in breast cancer patients with AF during adjuvant hormonal therapy.

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

Int J Cardiol: 31 Jan 2021; 324:78-83
Pacholczak-Madej R, Bazan-Socha S, Zaręba L, Undas A, Dropiński J
Int J Cardiol: 31 Jan 2021; 324:78-83 | PMID: 32931852
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Impact:
Abstract

Regional variation in patients and outcomes in the GLOBAL LEADERS trial.

Gao C, Takahashi K, Garg S, Hara H, ... Onuma Y, Serruys PW
Background
Despite the overall neutral results of the GLOBAL-LEADERS trial, results from a prespecified subgroup analysis showed that patients from Western Europe had a significantly lower rate of the primary endpoint when treated with ticagrelor monotherapy. Therefore, we aimed to examine the regional disparities in patients\' baseline characteristics and their response to ticagrelor monotherapy.
Methods
Patients\' baseline characteristics and the treatment effects of ticagrelor combined with aspirin for 1 month, followed by ticagrelor monotherapy for 23-months versus 12-months of standard dual antiplatelet therapy (DAPT) were compared according to participating countries. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at two years.
Results
Significant variances in patients\' baseline characteristics were found between participating countries. The primary endpoint varied significantly according to the country (P = 0.027). Patients from France (1.6% versus 5.2%, HR: 0.31, 95%CI: 0.13-0.73) and The Netherlands (2.4% versus 4.8%, HR, 0.50, 95%CI: 0.26-0.94) had lower rates of the primary endpoint when allocated to ticagrelor monotherapy, compared with the standard DAPT regimen. Of the 26 baseline and post-randomization factors explored, variance in the rate of complex PCI between countries was identified as the top contributor to this regional interaction.
Conclusions
Patients\' baseline characteristics varied between participating countries in the GLOBAL-LEADERS trial. There is a significant regional variance in the treatment effect of ticagrelor monotherapy, which could partly be explained by the differences in complex PCI being performed.
Clinical trial registration
ClinicalTrials.gov (NCT01813435).

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

Int J Cardiol: 31 Jan 2021; 324:30-37
Gao C, Takahashi K, Garg S, Hara H, ... Onuma Y, Serruys PW
Int J Cardiol: 31 Jan 2021; 324:30-37 | PMID: 32941872
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Abstract

Diagnostic utility of right atrial reservoir strain to identify elevated right atrial pressure in heart failure.

Miah N, Faxén UL, Lund LH, Venkateshvaran A
Background
Accurate non-invasive estimation of right atrial pressure (RAP) is essential to assess volume status and optimize therapy in heart failure (HF). This study aimed to evaluate the utility of right atrial reservoir strain (RASr) assessed by speckle-tracking echocardiography to identify elevated RAP in HF and compare diagnostic performance with estimated RAP employing inferior vena cava size and collapsibility (RAP), in addition to RA area.
Method
Association between RASr and invasive RAP (RAP) was examined in 103 HF subjects that underwent standard echocardiography with speckle-tracking strain analysis directly followed by right heart catheterization. The discriminatory ability of RASr to identify RAP > 7 mmHg was evaluated and compared with RAP and RA area.
Results
RASr demonstrated association with RAP (β = -0.41, p < 0.001) and was an independent predictor when adjusted for potential confounders (β = -0.25, p < 0.001). Further, RASr showcased strong discriminatory ability to identify subjects with RAP > 7 mmHg (AUC = 0.78; 95% CI 0.68-0.87; p < 0.001). At a cut-off value of -15%, RASr displayed 78% sensitivity and 72% specificity to identify elevated RAP In comparison, RAP (AUC = 0.71; 95% CI 0.61-0.81; p < 0.001) demonstrated 89% sensitivity and 32% specificity with high false positive rate. RA area (AUC = 0.66; 95% CI 0.55-0.76, p = 0.005) displayed 64% sensitivity and 53% specificity.
Conclusions
RASr demonstrates good ability to identify elevated RAP and relatively stronger diagnostic performance when compared with conventional non-invasive measures. RASr may be useful as a novel noninvasive estimate of RAP in HF management.

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

Int J Cardiol: 31 Jan 2021; 324:227-232
Miah N, Faxén UL, Lund LH, Venkateshvaran A
Int J Cardiol: 31 Jan 2021; 324:227-232 | PMID: 32941871
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Abstract

Cardiac implantable device outcomes and lead survival in adult congenital heart disease.

Bowman HC, Shannon KM, Biniwale R, Moore JP
Background
Long-term outcomes of cardiac implantable electronic devices (CIEDs) are ill-defined in adult congenital heart disease (ACHD).
Objective
To assess outcomes of transvenous (TV) and epicardial (EPI) CIEDs in ACHD.
Methods
A retrospective review of CIEDs implanted in patients >18 yrs. followed at the Ahmanson/UCLA ACHD Center was performed. Patients were grouped by implant approach. Primary outcomes included time to CIED dysfunction, lead dysfunction and unplanned CIED reintervention.
Results
Over a 27-year period, 283 CIEDs (208 TV, 75 EPI) were implanted in 260 ACHD patients. Dysfunction developed in 77 CIEDs (50 TV, 27 EPI) for which 62 underwent unplanned reintervention (47 TV, 15 EPI). Time to CIED dysfunction and unplanned reintervention did not differ by implant approach; however lead dysfunction was greater for EPI vs TV (HR 2.0, 95% CI 1.2-3.2, p = 0.01). Independent predictors of lead failure included cyanosis (HR 2.6, 95% CI 1.1-6.3; p = 0.03), implant indication other than bradycardia (HR 3.3, 95% CI 1.6-6.5; p < 0.01), right-sided Maze operation (HR 2.5, 95% CI 1.3-5.0; p = 0.01), and unipolar lead design (HR 4.5, 95% CI 1.8-11.5; p < 0.01). Importantly, EPI vs TV approach was not associated with lead dysfunction after adjusting for baseline covariates (HR 0.6, 95% CI 0.6-4.3; p = 0.3).
Conclusion
Overall CIED system dysfunction and reinterventions are similar, whereas lead dysfunction is greater among EPI than TV devices. Patient and procedural differences, rather than EPI vs TV implant approach alone, appear to drive CIED lead outcomes in the ACHD population.

Published by Elsevier B.V.

Int J Cardiol: 31 Jan 2021; 324:52-59
Bowman HC, Shannon KM, Biniwale R, Moore JP
Int J Cardiol: 31 Jan 2021; 324:52-59 | PMID: 32941867
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Abstract

Are all left bundle branch blocks the same? Myocardial mechanical implications by cardiovascular magnetic resonance.

Baritussio A, Biglino G, Moharem-Elgamal S, De Garate E, ... Milano EG, Bucciarelli-Ducci C
Aims
Left bundle branch block (LBBB) is usually associated with structural myocardial diseases progressively leading to left ventricular (LV) dysfunction. We sought to determine the mechanical implications of LBBB (as defined based on Strauss\' criteria) by Cardiovascular Magnetic Resonance (CMR).
Method and results
We included consecutive patients referred to CMR to assess the structural cause of LBBB. CMR scans consisted of cine, stress perfusion, and late gadolinium enhancement (LGE) sequences. Myocardial deformation was assessed by tissue tracking analysis; LGE was quantified using the full width at half maximum method. We included 86 patients [63% male, 70 years (60-72)] with mean QRS duration 150 ± 13 msec. A structural disease was identified on CMR in 53% of patients (ischemic heart disease, IHD, 31%; non-ischemic heart disease, NIHD, 22%), while LBBB-related septal dyssynchrony (SD) was the only abnormality in 47%. LGE was found in 42% of patients. LVEF and myocardial deformation were impaired. Despite similar ECG characteristics, myocardial strain differed significantly between IHD, NIHD and SD patients, and patients with SD showed less impaired myocardial deformation. Indexed LV end-systolic volume and LGE extent were independently associated with impaired strain.
Conclusions
Patients with LBBB show different structural and mechanical properties, and LGE extent has an unfavourable effect on myocardial mechanics.

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

Int J Cardiol: 31 Jan 2021; 324:221-226
Baritussio A, Biglino G, Moharem-Elgamal S, De Garate E, ... Milano EG, Bucciarelli-Ducci C
Int J Cardiol: 31 Jan 2021; 324:221-226 | PMID: 32941866
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Abstract

High prevalence of subtle systolic and diastolic dysfunction in genotype-positive phenotype-negative relatives of dilated cardiomyopathy patients.

Paldino A, De Angelis G, Dal Ferro M, Faganello G, ... Merlo M, Sinagra G
Background
The early diagnosis of genetically determined dilated cardiomyopathy (DCM) could improve the prognosis in mutation carriers. Left ventricular global longitudinal strain (LV GLS) and peak left atrial longitudinal strain (PALS) are promising techniques for the detection of subtle systolic and diastolic dysfunction. We sought to evaluate the prevalence of subtle systolic and diastolic dysfunction by LV GLS and PALS in a cohort of genotype-positive phenotype-negative (GPFN) DCM relatives.
Methods and results
In this retrospective study, we analyzed echocardiograms of forty-one GPFN relatives of DCM patients. They were compared with age and sex matched healthy individuals (control group). Reduced LV GLS and PALS were defined as >18% and <23.1%, respectively. GPFN relatives (37 ± 14 years, 48.8% male) and controls were similar according to standard echocardiographic measurements. Conversely, LV GLS was -18.8 ± 2.7% in the GPFN group vs. -24.0 ± 1.8% in the control group (p < 0.001). Twenty subjects (48.8%) in the GPFN group and no subjects in the control group had a reduced LV GLS. PALS was 29.2 ± 6.7% in the GPFN group vs. 40.8 ± 8.5% in the control group (p < 0.001). Seven subjects (18.4%) in the GPFN group and one (2%) in the control group had a reduced PALS. A cohort of 17 genotype-negative phenotype-negative relatives showed higher values of LV GLS compared to GPFN.
Conclusions
Despite standard echocardiographic parameters are within the normal range, LV GLS and PALS are lower in GPFN relatives of DCM patients when compared to healthy individuals, suggesting a consistent proportion of subtle systolic and diastolic dysfunction in this population.

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

Int J Cardiol: 31 Jan 2021; 324:108-114
Paldino A, De Angelis G, Dal Ferro M, Faganello G, ... Merlo M, Sinagra G
Int J Cardiol: 31 Jan 2021; 324:108-114 | PMID: 32949639
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Impact:
Abstract

Clinical impact of red blood cell transfusion on adverse clinical events in acute heart failure patients with anemia.

Higuchi S, Hata N, Shibata S, Hirabuki K, ... Hasegawa H, Matsuda T
Background
Anemia has been recognized as an important comorbidity in patients with acute heart failure (AHF) and is associated with adverse clinical events. However, the clinical impact of red blood cell (RBC) transfusion in such patients is unclear.
Method
This study was a retrospective single-center registry including AHF patients admitted to Kyorin University Hospital between 2007 and 2014. Anemia was defined as a hemoglobin level < 130 g/L in males or < 120 g/L in females. Those with major bleeding with a fall in hemoglobin concentration of >20 g/L were excluded. AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were evaluated.
Results
Of 501 AHF patients, 38 were excluded owing to major bleeding; finally, 463 (age, 77 ± 11 years; males, 58%) were evaluated. RBC transfusion during hospitalization was performed in 112 patients (24%). Hemoglobin level on admission was 105 ± 16 g/L (transfusion, 89 ± 17 g/L; no transfusion, 110 ± 12 g/L; p < 0.001). AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were observed in 46 (10%), 16 (3%), and 121 (26%) patients, respectively. Univariate Cox regression analysis demonstrated that RBC transfusion was not associated with AHF readmission at 3 months (hazard ratio: 0.80; 95% confidence interval: 0.39-1.66) The association did not differ at any hemoglobin concentration or left ventricular ejection fraction value. Multivariate Cox regression analysis revealed similar results. Furthermore, RBC transfusion was not correlated with in-hospital and 2-year all-cause mortality.
Conclusions
RBC transfusion was not associated with AHF readmission or all-cause mortality.

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

Int J Cardiol: 31 Jan 2021; 324:102-107
Higuchi S, Hata N, Shibata S, Hirabuki K, ... Hasegawa H, Matsuda T
Int J Cardiol: 31 Jan 2021; 324:102-107 | PMID: 32946954
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Impact:
Abstract

Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA).

Ammirati E, Brambatti M, Braun OÖ, Shah P, ... Frigerio M, Adler ED
Background
Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown.
Methods
We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months.
Results
The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU.
Conclusions
Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.

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

Int J Cardiol: 31 Jan 2021; 324:122-130
Ammirati E, Brambatti M, Braun OÖ, Shah P, ... Frigerio M, Adler ED
Int J Cardiol: 31 Jan 2021; 324:122-130 | PMID: 32950592
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Impact:
Abstract

MicroRNA-3614 regulates inflammatory response via targeting TRAF6-mediated MAPKs and NF-κB signaling in the epicardial adipose tissue with coronary artery disease.

Huang W, Wu X, Xue Y, Zhou Y, ... Yang W, Wei Y
Objective
The inflammatory status of epicardial adipose tissue (EAT) is one of the factors leading to the development of related diseases such as coronary artery disease (CAD). The thickness of CAD EAT increases and is accompanied with increased macrophage infiltration and heightened inflammatory responses. However, microRNAs (miRNAs) regulating the inflammatory responses of macrophages in CAD EAT remain unclear.
Method
miRNA expression profiles of CAD EATs and non-CAD EATs were determined by miRNA microarrays. Quantitative real-time reverse transcription-polymerase chain reaction, Western blotting, immunohistochemical assay, and fluorescence in-situ hybridization were adopted to detect miR-3614 expression and function in EATs and macrophages. The interaction between miR-3614 and tumor necrosis factor receptor-associated factor 6 (TRAF6) was identified using an online website combined with a dual-luciferase reporter assay. Enzyme-linked immunosorbent assay was performed to detect the expression of inflammatory cytokines.
Results
The decreased expression of miR-3614 was identified in CAD EAT. The level of miR-3614 was down-regulated by lipopolysaccharide (LPS) in macrophages, whereas LPS-induced inflammatory injury can be reduced by miR-3614 overexpression. TRAF6 was predicted and verified to be a target of miR-3614. The phosphorylated levels of kinases in the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways were inhibited by miR-3614 overexpression. Importantly, the knockdown of TRAF6 inhibited the LPS-induced inflammatory cytokine expressions in cells.
Conclusion
A novel negative feedback loop by miR-3614 possibly contribute to the regulation of inflammatory processes via targeting the TRAF6/MAPK/NF-κB pathway in EATs and prevents an overwhelming inflammatory response.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 31 Jan 2021; 324:152-164
Huang W, Wu X, Xue Y, Zhou Y, ... Yang W, Wei Y
Int J Cardiol: 31 Jan 2021; 324:152-164 | PMID: 32950591
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Impact:
Abstract

Assessing QT interval in COVID-19 patients:safety of hydroxychloroquine-azithromycin combination regimen.

Bernardini A, Ciconte G, Negro G, Rondine R, ... Menicanti L, Pappone C
Background
Hydroxychloroquine (HCQ) and azithromycin (AZT) have been proposed for COVID-19 treatment. Data available in the literature reported a potential increased risk of fatal arrhythmias under these therapies. The aim of this study was to assess the effects of these drugs on QT interval and outcome in a COVID-19 population.
Method
A total of 112 consecutive COVID-19 patients were included in this analysis and were divided in 3 groups according to the receiving therapeutic regimens: 19 (17%) patients in Group 1 (no treatment), 40 (36%) in Group 2 (HCQ only), 53 (47%) in Group 3 (HCQ/AZT).
Results
A prolonged QTc interval was found in 61% of patients treated with HCQ alone or in combination with AZT, but only 4 (4%) patients showed a QTc > 500 ms. HCQ/AZT combination determined a greater increase of QTc duration compared to the other two strategies (Group 3 452 ± 26.4 vs Group 2 436.3 ± 28.4 vs Group 1 424.4 ± 24.3 ms, respectively; p < 0.001). Multivariate analysis demonstrated that HCQ/AZT combination (OR 9.02, p = 0.001) and older age (OR 1.04, p = 0.031) were independent predictors of QTc prolongation. The risk increased with age (incremental utility analysis p = 0.02). Twenty patients (18%) died, and no cardiac arrest neither arrhythmic fatalities were documented.
Conclusions
The HCQ/AZT combination therapy causes a significantly increase of QT interval compared to HCQ alone. Older patients under such regimen are at higher risk of experiencing QT prolongation. The use of such drugs may be considered as safe relating to arrhythmic risk in the treatment of COVID-19 patients as no arrhythmic fatalities occurred.

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

Int J Cardiol: 31 Jan 2021; 324:242-248
Bernardini A, Ciconte G, Negro G, Rondine R, ... Menicanti L, Pappone C
Int J Cardiol: 31 Jan 2021; 324:242-248 | PMID: 32956782
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Impact:
Abstract

Association between time of out-of-hospital cardiac arrest and survival: Examination of the all-Japan Utstein registry and comparison with the 2005 and 2010 international resuscitation guidelines.

Kato K, Otsuka T, Seino Y, Tahara Y, ... Tsutsui H, Japanese Circulation Society with Resuscitation Science Study (JCS-ReSS) Group
Background
Existing studies have yielded conflicting results regarding the relationship between the time of occurrence of out-of-hospital cardiac arrests and the associated outcomes. We examined whether the one-month survival rate for out-of-hospital cardiac arrests differed depending on whether the cardiac arrest occurred during the day or night. Further, we examined whether this rate differed when comparing the period succeeding the 2005 International Resuscitation Guidelines (2006-2010) with that following the 2010 guidelines (2011-2015).
Method
Using data from the All-Japan Utstein Registry for 2006-2015, adult out-of-hospital cardiac arrest patients whose collapse was witnessed and for whom the collapse-to-hospital-arrival interval was shorter than 120 min were included in this study. Patients were categorized in terms of whether their arrest occurred during the post-2005- or post-2010-guideline period. The primary measure was the one-month survival with a favorable neurological outcome.
Results
Of 481,624 cases analyzed, 20% occurred at night. For both guideline periods, nighttime out-of-hospital cardiac arrests were associated with significantly lower one-month survival rates than daytime incidents (used as a reference; adjusted odds ratio: 0.69 and 0.63, 95% confidence interval: 0.65-0.73 and 0.60-0.65, and P < 0.001 and <0.001 for the 2005 and 2010 guideline periods, respectively).
Conclusions
One-month survival with a favorable neurological outcome was significantly lower for patients who experienced nighttime out-of-hospital cardiac arrests, compared to daytime out-of-hospital cardiac arrests. This could be addressed by improving cardiopulmonary resuscitation training for bystanders and expanding and improving nighttime emergency medical services.

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

Int J Cardiol: 31 Jan 2021; 324:214-220
Kato K, Otsuka T, Seino Y, Tahara Y, ... Tsutsui H, Japanese Circulation Society with Resuscitation Science Study (JCS-ReSS) Group
Int J Cardiol: 31 Jan 2021; 324:214-220 | PMID: 32961310
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Impact:
Abstract

Impact of instantaneous wave-free ratio on graft failure after coronary artery bypass graft surgery.

Wada T, Shiono Y, Kubo T, Honda K, ... Nishimura Y, Akasaka T
Background
We aimed to assess an impact of instantaneous wave-free ratio (iFR) on a graft failure after coronary artery bypass grafting (CABG).
Methods and results
A total of 131 coronary arteries from 88 patients who underwent invasive coronary angiography, intracoronary pressure measurements, CABG, and scheduled follow-up coronary computed tomography angiography within one year were investigated. All studied arteries had FFR <0.80. The rate of graft failure was significantly higher in vessels with negative iFR (>0.89) than in those with positive iFR (<0.89) (25.7% vs. 7.3%, p = 0.012). The graft failure rates increased as the preoperative iFR values rose (iFR <0.80, 3.3%; iFR: 0.80-0.84, 5.6%; iFR: 0.85-0.89, 16.0%; iFR: 0.90-0.94, 28.0%; and iFR: 0.95-1.00, 50.0%; p = 0.002). A cut-off value of iFR to predict graft failures was determined as 0.84 by receiver-operating characteristic curve analysis with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 88%, 62%, 25%, 97%, and 66%, respectively.
Conclusions
The risk of graft failure becomes higher, as the preoperative iFR increases. The graft failure is significantly more frequent when a bypass graft is anastomosed on vessels with negative iFR than those with positive iFR.

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

Int J Cardiol: 31 Jan 2021; 324:23-29
Wada T, Shiono Y, Kubo T, Honda K, ... Nishimura Y, Akasaka T
Int J Cardiol: 31 Jan 2021; 324:23-29 | PMID: 32966833
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Impact:
Abstract

Short term outcomes of Impella in cardiogenic shock: A review and meta-analysis of observational studies.

Iannaccone M, Albani S, Giannini F, Colangelo S, ... de Ferrari GM, Colombo A
Introduction
The clinical impact of invasive hemodynamic support with Impella in patients with cardiogenic shock (CS) remains to be defined.
Method
Only studies including patients treated with Impella in CS were selected. The primary endpoint was short term mortality, while secondary endpoints were major vascular complications and major bleeding.
Results
17 studies and 3933 patients were included in the analysis. Median age was 61.9 (IQR 59.2-63.5) years, CS was mainly related to acute coronary syndrome (ACS): 79.6% (IQR 75.1-79.6). Thirty-day mortality was 47.8% (CI 43.7-52%). Based on metaregression analysis, the Impella 5.0 (point estimate -0.006, 95% CI -0.01 - - 0.02, p < 0.01) and the Impella CP (point estimate -0.007, 95% CI -0.01 - - 0.03, p < 0.01) devices were related to a higher survival rate, whereas the Impella 2.5 was not. Furthermore, a correlation with reduced mortality was found when Impella was initiated in CS not complicated by cardiac arrest (CA), and before revascularization, (point estimate 0.01, 95% CI 0.002-0.02, p < 0.01 and point estimate -0.02, 95% CI 0.023-0.01, p < 0.001 respectively). The vascular complication and major bleeding rate were 7.4% (95% CI 5.6-9.6%) and 15.2% (95% CI 10.7-21%) respectively, and were associated with older age and comorbidities, while the implantation of an Impella CP/2.5 L was associated with fewer complications.
Conclusions
Despite the use of Impella the 30 day mortality of CS still remains high. Our data suggest that the use of an Impella CP, initiation of Impella prior to PCI and in patients without cardiac arrest was correlated with outcome improvements.

Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Jan 2021; 324:44-51
Iannaccone M, Albani S, Giannini F, Colangelo S, ... de Ferrari GM, Colombo A
Int J Cardiol: 31 Jan 2021; 324:44-51 | PMID: 32971148
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Impact:
Abstract

An exploration of the heterogeneity in effects of SGLT2 inhibition on cardiovascular and all-cause mortality in the EMPA-REG OUTCOME, CANVAS Program, DECLARE-TIMI 58, and CREDENCE trials.

Yu J, Zhou Z, Mahaffey KW, Matthews DR, ... Neal B, Arnott C
Background
Large-scale outcome trials of sodium glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes have identified consistent effects on major adverse cardiovascular events, heart failure, and progression of kidney disease. However, the magnitude of effects on cardiovascular and all-cause death appeared to vary between some of the studies.
Methods
We explored the impact of differences in trial methodologies, participant characteristics, types of deaths, follow-up duration, effects on intermediate markers of risk, and drug selectivity for SGLT2 on the magnitude of the protective effect against fatal events achieved in the 4 trials.
Results
The trial populations differed substantively in the proportions with baseline atherosclerotic cardiovascular disease history (99.2% in EMPA-REG OUTCOME to 40.6% in DECLARE-TIMI 58), and macroalbuminuria (88.0% in CREDENCE to 7.6% in the CANVAS Program). Meta-regression analyses identified no clear effect of these (both P > 0.09) or other participant characteristics on mortality benefits (all P > 0.55). Other differences between the trials (duration, selectivity of the SGLT2 inhibitor, or effects on intermediate markers of risk) also did not explain the heterogeneity in effects on mortality observed (all P > 0.30).
Conclusion
No clear explanation for the statistical evidence of heterogeneity in effects of SGLT2 inhibition on fatal outcomes between the trials could be identified. While the analyses had limited statistical power, these results raise the possibility that the observed variations in treatment effects on fatal outcomes between trials may be at least partly due to chance.

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

Int J Cardiol: 31 Jan 2021; 324:165-172
Yu J, Zhou Z, Mahaffey KW, Matthews DR, ... Neal B, Arnott C
Int J Cardiol: 31 Jan 2021; 324:165-172 | PMID: 32979427
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Impact:
Abstract

ECG changes at rest and during exercise in lowlanders with COPD travelling to 3100 m.

Carta AF, Bitos K, Furian M, Mademilov M, ... Bloch KE, Ulrich S
Background
The incidence and magnitude of cardiac ischemia and arrhythmias in patients with chronic obstructive pulmonary disease (COPD) during exposure to hypobaric hypoxia is insufficiently studied. We investigated electrocardiogram (ECG) markers of ischemia at rest and during incremental exercise testing (IET) in COPD-patients travelling to 3100 m.
Study design and methods
Lowlanders (residence <800 m) with COPD (forced volume in the first second of expiration (FEV) 40-80% predicted, oxygen saturation (SpO) ≥92%, arterial partial pressure of carbon dioxide (PaCO) <6 kPa at 760 m) aged 18 to 75 years, without history of cardiovascular disease underwent 12‑lead ECG recordings at rest and during cycle IET to exhaustion at 760 m and after acute exposure of 3 h to 3100 m. Mean ST-changes in ECGs averaged over 10s were analyzed for signs of ischemia (≥1 mm horizontal or downsloping ST-segment depression) at rest, peak exercise and 2-min recovery.
Results
80 COPD-patients (51% women, mean ± SD, 56.2 ± 9.6 years, body mass index (BMI) 27.0 ± 4.5 kg/m, SpO 94 ± 2%, FEV 63 ± 10% prEd.) were included. At 3100 m, 2 of 53 (3.8%) patients revealed ≥1 mm horizontal ST-depression during IET vs 0 of 64 at 760 m (p = 0.203). Multivariable mixed regression revealed minor but significant ST-depressions associated with altitude, peak exercise or recovery and rate pressure product (RPP) in multiple leads.
Conclusion
In this study, ECG recordings at rest and during IET in COPD-patients do not suggest an increased incidence of signs of ischemia with ascent to 3100 m. Whether statistically significant ST changes below the standard threshold of clinical relevance detected in multiple leads reflect a risk of ischemia during prolonged exposure remains to be elucidated.

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Jan 2021; 324:173-179
Carta AF, Bitos K, Furian M, Mademilov M, ... Bloch KE, Ulrich S
Int J Cardiol: 31 Jan 2021; 324:173-179 | PMID: 32987054
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Impact:
Abstract

Identification of high-risk Fontan candidates by intraoperative pulmonary flow study.

Baek JS, Park CS, Yun TJ, Bae EJ
Background
Pre-Fontan risk stratification is still less than optimal. We aimed to evaluate the effectiveness of intraoperative pulmonary flow study (IOFS), in combination with conventional preoperative evaluation, in the identification of high-risk candidates for the Fontan operation.
Method
Data from 37 patients (age: 38.1 ± 4.9 months) who underwent the Fontan operation with IOFS were retrospectively reviewed. After anastomosing the Gore-Tex vascular graft to the confluent pulmonary artery, IOFS was performed through the graft at various cardiac indices (CI) (1-4 L/min/m) generated from a roller pump. Mean pulmonary artery pressure (mPAP) and left atrial pressure (LAP) were recorded. The patients were divided into two groups: those who required Fontan circuit fenestration (group Ff) and those who did not (group Fn).
Results
Eleven patients (29.7%) required fenestration, intraoperatively (n = 4) and postoperatively (n = 7), due to hemodynamic instability. Heterotaxy syndrome (P = 0.005) and atrioventricular valvar regurgitation (P = 0.04) were more frequent, and ventricle posterior wall thickness (VPWT) was higher (P = 0.024) in group Ff. On IOFS, the increase in mPAP by CI was sharper in group Ff than in group Fn (P < 0.001) owing to an increase in LAP. On multivariable analysis, mPAP at a CI of 3.0 L/min/m from IOFS was the only predictor of fenestration and correlated with preoperative VPWT (R = 0.543, P = 0.001).
Conclusions
IOFS may be helpful to identify high-risk Fontan candidates, and high mPAP at CI of 3.0 L/min/m on IOFS is a significant predictor of the requirement for fenestration. VPWT is an important preoperative risk factor which correlates with the IOFS results.

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

Int J Cardiol: 31 Jan 2021; 324:60-65
Baek JS, Park CS, Yun TJ, Bae EJ
Int J Cardiol: 31 Jan 2021; 324:60-65 | PMID: 32987053
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Impact:
Abstract

Impact of disease stage on the performance of strain markers in the prediction of atrial fibrillation.

Ramkumar S, Pathan F, Kawakami H, Ochi A, ... Potter EL, Marwick TH
Background
Assessing atrial fibrillation (AF) risk may be useful in primary prevention (PP; people with risk factors) and secondary prevention (SP; eg. embolic stroke of unknown source). We sought whether disease stage influenced the prediction of AF by echocardiography.
Methods
We compared a PP cohort (351 community-based participants ≥65 years with ≥1 risk factor for AF) and a SP cohort (453 patients after transient ischemic attack or stroke). LV global longitudinal strain (GLS) and left atrial reservoir strain (LARS) were measured from DICOM images. AF was diagnosed by 12 lead ECG, Holter or by single lead monitor over median follow-up of 22 months (PP) and 35 months (SP). The clinical and echocardiographic characteristics of those with AF were compared to those in sinus rhythm. Nested Cox-regression models assessed for independent and incremental predictive value of LARS and GLS in both cohorts.
Results
AF developed in 42 PP (12%) and 60 SP (13%), and was associated with age, higher CHARGE-AF score, increased LA volume and LV mass (p < 0.05). Patients developing AF had reduced GLS (17 ± 3.5% vs. 20 ± 3%, p < 0.001) and LARS (28 ± 11% vs. 35 ± 8%, p < 0.001). However, the predictive value of both GLS (area under the ROC curve 0.83 vs 0.56, p < 0.001) and LARS (0.83 vs 0.57, p < 0.001) was greater in SP than PP. LARS was independently associated with AF in both cohorts (p < 0.05), but GLS was only independently associated in the SP cohort.
Conclusion
AF risk assessment with LARS is suitable for different risk cohorts, but GLS is more useful in SP.

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

Int J Cardiol: 31 Jan 2021; 324:233-241
Ramkumar S, Pathan F, Kawakami H, Ochi A, ... Potter EL, Marwick TH
Int J Cardiol: 31 Jan 2021; 324:233-241 | PMID: 32987052
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Impact:
Abstract

Systolic dysfunction of the subpulmonary left ventricle is associated with the severity of heart failure in patients with a systemic right ventricle.

Surkova E, Segura T, Dimopoulos K, Bispo D, ... Gatzoulis MA, Li W
Background
The study aimed to assess the relation between echocardiographic parameters of subpulmonary left ventricular (LV) size and function, and the severity of heart failure in patients with a systemic right ventricle (SRV).
Methods and results
A total of 157 patients (89 post Mustard/Senning operations, 68 with congenitally corrected transposition of great arteries [ccTGA]) were included. The size and function of the SRV and subpulmonary LV were assessed on the most recent echocardiographic exam. Clinical data were collected from the electronic records. The majority (133, 84.7%) were in NYHA functional class 1-2. Median BNP concentration was 79.5[38.3-173.3] ng/l, and 100 (63.7%) patients were receiving heart failure therapy. Both LV and SRV fractional area change (FAC) differed significantly between patients with NYHA class 1-2 vs 3-4 (48[41.5-52.8]% vs 34[28.6-38.6]%, p < 0.0001 and 29.5[23-35]% vs 22[20-27]%, p < 0.0001, respectively), but LV FAC had a higher discriminative power for functional class >2 than SRV FAC (AUC 0.90, p < 0.0001 vs 0.79; p < 0.0001, respectively). A LV FAC cut-off value <39.2% had the highest accuracy in identifying patients with NYHA class 3-4 (sensitivity 83% and specificity 88%). In multivariable logistic regression analysis, LV FAC and SRV FAC independently associated to NYHA class 3-4 (OR 0.80 [95%CI 0.72-0.88], p < 0.0001 and OR 0.85 [95%CI 0.76-0.96], p = 0.007, respectively).
Conclusions
Subpulmonary LV systolic dysfunction is associated with NYHA functional class 3-4 in patients with ccTGA or after Mustard or Senning operation. Careful evaluation of the subpulmonary LV should be a part of the routine assessment of patients with a SRV.

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

Int J Cardiol: 31 Jan 2021; 324:66-71
Surkova E, Segura T, Dimopoulos K, Bispo D, ... Gatzoulis MA, Li W
Int J Cardiol: 31 Jan 2021; 324:66-71 | PMID: 32987051
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Impact:
Abstract

Higher oxidized high-density lipoprotein to apolipoprotein A-I ratio is associated with high-risk coronary plaque characteristics determined by CT angiography.

Suruga K, Miyoshi T, Kotani K, Ichikawa K, ... Morita H, Ito H
Background
Oxidized high-density lipoprotein (oxHDL), unlike native HDL, is characterized by reduced cholesterol efflux capability and anti-inflammatory properties. The ratio of oxHDL to apolipoprotein A-I (oxHDL/apoAI) is a possible marker of dysfunctional HDL. The aim of this study was to evaluate the association between oxHDL/apoAI and coronary plaque characteristics that increase the likelihood of cardiovascular events as determined by coronary computed tomography (CT) angiography.
Methods
A total of 297 patients (mean age; 67 years, men; 63%) who underwent coronary CT angiography for suspected stable coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined by three characteristics: positive remodeling; low-density plaques; and spotty calcification. Significant stenosis was defined as a luminal narrowing of >70%. Serum concentrations of oxHDL were measured using an enzyme-linked immunosorbent assay.
Results
Patients with higher oxHDL/ApoAI showed significantly greater prevalence of HRP (p = 0.03) and significant stenosis (p < 0.01) compared with patients with low oxHDL/ ApoAI. The multivariate logistic analysis demonstrated that oxHDL/ApoAI significantly associated with the presence of HRP and significant coronary stenosis (p = 0.01 and < 0.01). In the follow-up study including 243 patients for a median period of 1.8 years, univariate cox regression analysis showed that oxHDL/ApoAI, HRP and significant stenosis were significant predictors of cardiovascular events.
Conclusions
A high oxHDL/apoAI was associated with the presence of HRP and significant stenosis determined by coronary CT angiography, which can lead to cardiovascular events in patients with suspected stable CAD.

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

Int J Cardiol: 31 Jan 2021; 324:193-198
Suruga K, Miyoshi T, Kotani K, Ichikawa K, ... Morita H, Ito H
Int J Cardiol: 31 Jan 2021; 324:193-198 | PMID: 32987049
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Impact:
Abstract

The role of anti-hypertensive treatment, comorbidities and early introduction of LMWH in the setting of COVID-19: A retrospective, observational study in Northern Italy.

Desai A, Voza G, Paiardi S, Teofilo FI, ... Voza A, Humanitas COVID-19 task force
Background
There is a great deal of debate about the role of cardiovascular comorbidities and the chronic use of antihypertensive agents (such as ACE-I and ARBs) on mortality on COVID-19 patients. Of note, ACE2 is responsible for the host cell entry of the virus.
Methods
We extracted data on 575 consecutive patients with laboratory-confirmed SARS-CoV-2 infection admitted to the Emergency Department (ED) of Humanitas Center, between February 21 and April 14, 2020. The aim of the study was to evaluate the role of chronic treatment with ACE-I or ARBs and other clinical predictors on in-hospital mortality in a cohort of COVID-19 patients.
Results
Multivariate analysis showed that a chronic intake of ACE-I was associated with a trend in reduction of mortality (OR: 0.53; 95% CI: 0.27-1.03; p = 0.06), differently from a chronic intake of ARB (OR: 1.1; 95% CI: 0.5-2.8; p=0.8). Increased age (ORs ranging from 3.4 to 25.2 and to 39.5 for 60-70, 70-80 and >80 years vs <60) and cardiovascular comorbidities (OR: 1.90; 95% CI: 1.1-3.3; p = 0.02) were confirmed as important risk factors for COVID-19 mortality. Timely treatment with low-molecular-weight heparin (LMWH) in ED was found to be protective (OR: 0.36; 95% CI: 0.21-0.62; p < 0.0001).
Conclusions
This study can contribute to understand the reasons behind the high mortality rate of patients in Lombardy, a region which accounts for >50% of total Italian deaths. Based on our findings, we support that daily intake of antihypertensive medications in the setting of COVID-19 should not be discontinued and that a timely LMWH administration in ED has shown to decrease in-hospital mortality.

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

Int J Cardiol: 31 Jan 2021; 324:249-254
Desai A, Voza G, Paiardi S, Teofilo FI, ... Voza A, Humanitas COVID-19 task force
Int J Cardiol: 31 Jan 2021; 324:249-254 | PMID: 32980434
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Impact:
Abstract

Antithrombotic therapy in patients with COVID-19? -Rationale and Evidence.

Godino C, Scotti A, Maugeri N, Mancini N, ... Margonato A, Landoni G

In patients with severe or critical Coronavirus disease 2019 (COVID-19) manifestations, a thromboinflammatory syndrome, with diffuse microvascular thrombosis, is increasingly evident as the final step of pro-inflammatory cytokines storm. Actually, no proven effective therapies for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exist. Preliminary observations on anticoagulant therapy appear to be associated with better outcomes in moderate and severe COVID-19 patients with signs of coagulopathy and in those requiring mechanical ventilation. The pathophysiology underlying the prothrombotic state elicited by SARS-CoV-2 outlines possible protective mechanisms of antithrombotic therapy (in primis anticoagulants) for this viral illness. The indications for antiplatelet/anticoagulant use (prevention, prophylaxis, therapy) are guided by the clinical context and the COVID-19 severity. We provide a practical approach on antithrombotic therapy management for COVID-19 patients from a multidisciplinary point of view.

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

Int J Cardiol: 31 Jan 2021; 324:261-266
Godino C, Scotti A, Maugeri N, Mancini N, ... Margonato A, Landoni G
Int J Cardiol: 31 Jan 2021; 324:261-266 | PMID: 33002521
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Impact:
Abstract

Impact of predictive value of Fibrosis-4 index in patients hospitalized for acute heart failure.

Shibata N, Kondo T, Kazama S, Kimura Y, ... Shimizu K, Murohara T
Background
Abnormalities in liver function tests commonly occur in patients with acute heart failure (AHF). The Fibrosis-4 (FIB4) index, a non-invasive and easily calculated marker, has been used for hepatic diseases and reflects adverse prognosis. It is not clearly established whether the FIB4 index at admission can predict adverse outcomes in patients with AHF.
Methods and results
From a multicenter AHF registry, we retrospectively evaluated 1162 consecutive patients admitted due to AHF (median age 78 [69-85] years and 702 patients [60.4%] were male). The FIB4 index at admission was calculated as: age (yrs) × aspartate aminotransferase [U/L]/(platelets count [10/μL] × √alanine aminotransferase [U/L]. The median value of the FIB4 index at admission was 2.79. All-cause mortality and rehospitalization due to HF at 12 months were investigated as a composite endpoint and occurred in 142 (12.2%) patients and 232 (20%) patients, respectively. Kaplan-Meyer analysis shows a significant increase in the composite endpoint from the first to fourth quartile group of the FIB4 index values (log-rank, p < 0.001). Multivariate Cox regression model revealed the FIB4 index was an independent risk predictor for composite endpoint in patients with AHF (3 months: HR ratio 1.013 [95% Confidence interval (CI):1.001-1.025]; p = 0.03, 12 months: HR 1.015 [95% CI:1.005-1.025]; p = 0.003, respectively). However, neither aspartate aminotransferase, alanine aminotransferase, nor platelet count was found to be a significant predictor.
Conclusions
Hepatic dysfunction evaluated with the FIB4 index at admission is a predictor of the composite endpoint of all-cause mortality and rehospitalization in AHF patients.

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

Int J Cardiol: 31 Jan 2021; 324:90-95
Shibata N, Kondo T, Kazama S, Kimura Y, ... Shimizu K, Murohara T
Int J Cardiol: 31 Jan 2021; 324:90-95 | PMID: 33007325
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Impact:
Abstract

Education and heart failure: New insights from the atherosclerosis risk in communities study and mendelian randomization study.

Liao LZ, Zhuang XD, Zhang SZ, Liao XX, Li WD
Introduction
We aim to characterize the nature and magnitude of the prospective association between education and incident heart failure (HF) in the Atherosclerosis Risk in Communities (ARIC) Study and investigate any causal relevance to the association between them.
Methods
The final sample size was 12,315 in this study. Baseline characteristics between education levels were compared using 1-way ANOVA test, the Kruskal-Wallis test, or the χ2 test. We used the Kaplan-Meier estimate to compute the cumulative incident of HF by education levels and the difference in estimate was compared using the log-rank test. Cox hazard regression models were used to explore the association between education levels and incident HF. Two-sample Mendelian randomization (MR) based on publicly available summary-level data from genome-wide association studies (GWASs) was used to estimate the causal influence of the education and incident HF.
Results
During a median follow-up of 25.1years, 2453 cases (19.9%) of incident HF occurred. After multiple adjustments in the final model, participants in the intermediate and advanced education levels were still associated with 18% and 21% decreased rate of incident HF separately. In MR analysis, we detected a protective causal association between education and HF (P=0.005).
Conclusions
Participants with higher education levels were associated with a decreased rate of incident HF. There was a causal association between education and HF.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 31 Jan 2021; 324:115-121
Liao LZ, Zhuang XD, Zhang SZ, Liao XX, Li WD
Int J Cardiol: 31 Jan 2021; 324:115-121 | PMID: 33017630
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Impact:
Abstract

Relationship between epicardial adipose tissue volume and coronary artery spasm.

Kataoka T, Harada K, Tanaka A, Onishi T, ... Amano T, Murohara T
Background
Epicardial adipose tissue (EAT) is considered to play a critical role in vascular endothelial function. Coronary artery spasm has been postulated to be a causal factor in vascular endothelial abnormalities and atherosclerosis. This study aimed to investigate the relationship between coronary artery spasm and EAT volume, total abdominal adipose tissue (AAT) area, and abdominal visceral adipose tissue (AVAT) area.
Method
Among patients undergoing coronary computed tomography (CT) to evaluate coronary artery disease, we identified 110 patients who did not have significant coronary artery stenosis and underwent a coronary spasm provocation test with cardiac catheterization. They were divided into two groups according to the results of the spasm provocation test: spasm-positive and spasm-negative. EAT volume, total AAT area, and AVAT area were evaluated using CT images.
Results
Seventy-seven patients were included in the spasm-positive group and 33 patients in the spasm-negative group. There were no significant differences in baseline clinical characteristics between the two groups, except for the prevalence of current smoking (48% vs. 27%, p = 0.04). EAT volume was significantly higher in the spasm-positive group (108 ± 38 mL vs. 87 ± 34 mL, p = 0.007), while no significant difference was seen in total AAT area (280 ± 113 cm vs. 254 ± 128 cm, p = 0.32) or AVAT area (112 ± 54 cm vs. 98 ± 55 cm, p = 0.27). Multivariate logistic analysis indicated that EAT volume (per 10 cm) (odds ratio, 1.198; 95% confidence interval, 1.035-1.388; p = 0.016) was a significant predictor of coronary artery spasm.
Conclusion
Our results suggest that EAT has a strong association with coronary artery spasm, while AAT may not.

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

Int J Cardiol: 31 Jan 2021; 324:8-12
Kataoka T, Harada K, Tanaka A, Onishi T, ... Amano T, Murohara T
Int J Cardiol: 31 Jan 2021; 324:8-12 | PMID: 33017629
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Impact:
Abstract

Revascularisation therapies improve the outcomes of ischemic stroke patients with atrial fibrillation and heart failure.

Pana TA, Mohamed MO, Clark AB, Fahy E, Mamas MA, Myint PK
Background
Atrial fibrillation (AF) and heart failure (HF) carry a poor prognosis in acute ischaemic stroke (AIS). The impact of revascularisation therapies on outcomes in these patients is not fully understood.
Method
National Inpatient Sample (NIS) AIS admissions (January 2004-September 2015) were included (n = 4,597,428). Logistic regressions analysed the relationship between exposures (neither AF nor HF-reference, AF-only, HF-only, AF + HF) and outcomes (in-hospital mortality, length-of-stay >median and moderate-to-severe disability on discharge), stratifying by receipt of intravenous thrombolysis (IVT) or endovascular thrombectomy (ET).
Results
69.2% patients had neither AF nor HF, 16.5% had AF-only, 7.5% had HF-only and 6.7% had AF + HF. 5.04% and 0.72% patients underwent IVT and/or ET, respectively. AF-only and HF-only were each associated with 75-85% increase in the odds of in-hospital mortality. AF + HF was associated with greater than two-fold increase in mortality. Patients with AF-only, HF-only or AF + HF undergoing IVT had better or at least similar in-hospital outcomes compared to their counterparts not undergoing IVT, except for prolonged hospitalisation. Patients undergoing ET with AF-only, HF-only or AF + HF had better (in-hospital mortality, discharge disability, all-cause bleeding) or at least similar (length-of-stay) outcomes to their counterparts not undergoing ET. Compared to AIS patients without AF, AF patients had approximately 50% and more than two-fold increases in the likelihood of receiving IVT or ET, respectively.
Conclusions
We confirmed the combined and individual impact of co-existing AF or HF on important patient-related outcomes. Revascularisation therapies improve these outcomes significantly in patients with these comorbidities.

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

Int J Cardiol: 31 Jan 2021; 324:205-213
Pana TA, Mohamed MO, Clark AB, Fahy E, Mamas MA, Myint PK
Int J Cardiol: 31 Jan 2021; 324:205-213 | PMID: 33022289
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Impact:
Abstract

Association between cardioplegia and postoperative atrial fibrillation in coronary surgery.

Mauro MD, Calafiore AM, Di Franco A, Nicolini F, ... Gaudino M, Lorusso R
Objective
The aim of this multicenter study was to evaluated whether cold or warm cardioplegia are associated with postoperative atrial fibrillation (POAF) and the prognostic role of the latter on early stroke and neurological mortality.
Method
This was a retrospective analysis of prospective collected data from 9 cardiac centers in Italy and the United States including patients undergoing surgery between 2010 and 2018. From the 9 institutional databases, 17,231 patients underwent isolated CABG on-pump, using either warm cardioplegia (n = 7730) or cold cardioplegia (n = 9501); among the latter group blood and crystalloid cardioplegia were used in 691 and 8810 patients, respectively. After matching, two pairs of 4162 patients (overall cohort 8324) were analyzed.
Results
In matched population, the rate of POAF was 18% (1472 cases), 15% (608) in warm group versus 21% (864) in cold group (p < 0.001). Multivariable analysis confirmed that cold cardioplegia was associated with higher rate of POAF, along with age, hypercholesterolemia, LVEF, reoperation, preoperative IABP, previous stroke, cardiopulmonary and cross-clamp. Moreover, cold cardioplegia as well as POAF increased the rate of postoperative stroke as well as early mortality and neurological mortality Propensity-weighted cohort included 11,830 (70%) patients out of 17,231. After adjustment, both cold blood and cold crystalloid cardioplegia negatively influenced POAF, stroke and neurological mortality.
Conclusions
Warm cardioplegia may reduce the rate of POAF in CABG patients with respect to cold cardioplegia, either blood or crystalloid. This has a prognostic impact on postoperative stroke and neurological mortality.

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

Int J Cardiol: 31 Jan 2021; 324:38-43
Mauro MD, Calafiore AM, Di Franco A, Nicolini F, ... Gaudino M, Lorusso R
Int J Cardiol: 31 Jan 2021; 324:38-43 | PMID: 33022288
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Impact:
Abstract

Remote ischemic preconditioning in isolated valve intervention. A pooled meta-analysis.

Moscarelli M, Angelini GD, Emanueli C, Suleiman S, ... Contegiacomo G, Punjabi PP
Objective
Recent studies have shown no benefits from remote ischemic preconditioning (RIPC) in patients undergoing coronary artery bypass surgery. One possible explanation is that given previous exposure to angina and ischemia/reperfusion injury these patients, may be already \'naturally preconditioned\'. The role of RIPC in a context of isolated valve intervention, both surgical and particularly transcatheter is less clear and remains under investigated, with few high-quality studies.
Methods
A systematic literature review identified 8 candidate studies that met the meta-analysis criteria. We analyzed outcomes of 610 subjects (312 RIPC and 298 SHAM) with random effects modeling. Each study was assessed for heterogeneity. The primary outcome was the extent of periprocedural myocardial injury, as reflected by the area under the curve for serum troponin concentration. Secondary endpoints included relevant intra- and post-operative outcomes; sensitivity and high-quality subgroup analysis was also carried out.
Results
Six and two studies reported the effect of RIPC in surgical and transcatheter valve intervention. There was a significant difference between-group in terms of periprocedural Troponin release (standardized mean difference (SMD: 0.74 [95% CI: 0.52; 0.95], p = 0.02) with no heterogeneity (χ 2.40, I 0%, p = 0.88). RIPC was not associated with any improvement in post-operative outcomes. No serious adverse RIPC related events were reported.
Conclusions
RIPC seems to elicit overall periprocedural cardioprotection in patients undergoing valvular intervention, yet with no benefit on early clinical outcomes.

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

Int J Cardiol: 31 Jan 2021; 324:146-151
Moscarelli M, Angelini GD, Emanueli C, Suleiman S, ... Contegiacomo G, Punjabi PP
Int J Cardiol: 31 Jan 2021; 324:146-151 | PMID: 33069785
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Impact:
Abstract

Revascularization versus medical therapy for the treatment of stable coronary artery disease: A meta-analysis of contemporary randomized controlled trials.

Laukkanen JA, Kunutsor SK
Background
We conducted a systematic review and meta-analysis of contemporary randomized controlled trials (RCTs) to compare clinical outcomes among stable coronary artery disease (CAD) patients treated with revascularization [percutaneous coronary intervention (PCI), coronary-artery bypass grafting (CABG) or both] plus medical therapy (MT) versus MT alone.
Methods
Prospective RCTs were sought from MEDLINE, Embase, The Cochrane Library, and Web of Science up to April 2020. Data was extracted on study characteristics, methods, and outcomes. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled for the composite of all-cause mortality, myocardial infarction (MI), revascularizations, rehospitalizations, or stroke; its individual components and other cardiovascular endpoints.
Results
Twelve unique RCTs comprising of 15,774 patients were included. There was no significant difference in all-cause mortality risk (0.95, 95% CI: 0.86-1.06); however, revascularization plus MT reduced the risk of the composite outcome of all-cause mortality, MI, revascularizations, rehospitalizations, or stroke (0.69, 95% CI: 0.55-0.87); unplanned revascularization (0.53, 95% CI: 0.40-0.71); and fatal MI (0.65, 95% CI: 0.49-0.84). Revascularization plus MT reduced the risk of stroke at 1 year (0.44, 95% CI: 0.30-0.65) and unplanned revascularization and the composite outcome of all-cause mortality, MI, revascularizations, rehospitalizations, or stroke at 2-5 years.
Conclusions
Revascularization plus MT does not confer survival advantage beyond that of MT among patients with stable CAD. However, revascularization plus MT may reduce the overall risk of the combined outcome of mortality, MI, revascularizations, rehospitalizations, or stroke, which could be driven by a decrease in the risk of unplanned revascularizations or fatal MI.

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

Int J Cardiol: 31 Jan 2021; 324:13-21
Laukkanen JA, Kunutsor SK
Int J Cardiol: 31 Jan 2021; 324:13-21 | PMID: 33068645
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Impact:
Abstract

Spontaneous reported cardiotoxicity induced by lopinavir/ritonavir in COVID-19. An alleged past-resolved problem.

Fresse A, Viard D, Romani S, Gérard A, ... Drici MD, French Network of Pharmacovigilance Centers

The antiretroviral drug lopinavir/ritonavir has been recently repurposed for the treatment of COVID-19. Its empirical use has been associated with multiple cardiac adverse reactions pertaining to its ancillary multi-channel blocking properties, vaguely characterized until now. We aimed to characterize qualitatively the cardiotoxicity associated with lopinavir/ritonavir in the setting of COVID-19. Spontaneous notifications of cardiac adverse drug reactions reported to the national Pharmacovigilance Network were collected for 8 weeks since March 1st 2020. The Nice Regional Center of Pharmacovigilance, whose scope of expertise is drug-induced long QT syndrome, analyzed the cases, including the reassessment of all available ECGs. QTc ≥ 500 ms and delta QTc > 60 ms from baseline were deemed serious. Twenty-two cases presented with 28 cardiac adverse reactions associated with the empirical use of lopinavir/ritonavir in a hospital setting. Most adverse reactions reflected lopinavir/ritonavir potency to block voltage-gated potassium channels with 5 ventricular arrhythmias and 17 QTc prolongations. An average QTc augmentation of 97 ± 69 ms was reported. Twelve QTc prolongations were deemed serious. Other cases were likely related to lopinavir/ritonavir potency to block sodium channels: 1 case of bundle branch block and 5 recurrent bradycardias. The incidence of cardiac adverse reactions of lopinavir/ritonavir was estimated between 0.3% and 0.4%. These cardiac adverse drug reactions offer a new insight in its ancillary multi-channel blocking functions. Lopinavir/ritonavir cardiotoxicity may be of concern for its empirical use during the COVID-19 pandemic. Caution should be exerted relative to this risk where lopinavir/ritonavir summary of product characteristics should be implemented accordingly.

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

Int J Cardiol: 31 Jan 2021; 324:255-260
Fresse A, Viard D, Romani S, Gérard A, ... Drici MD, French Network of Pharmacovigilance Centers
Int J Cardiol: 31 Jan 2021; 324:255-260 | PMID: 33075384
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Impact:
Abstract

Management perspectives from the 2019 Wuhan international workshop on fulminant myocarditis.

Veronese G, Ammirati E, Chen C, Klingel K, ... Cooper LT, Wang DW

Fulminant myocarditis (FM) is a form of acute myocardial inflammation leading to rapid-onset hemodynamic instability due to cardiogenic shock or life-threatening arrhythmias. As highlighted by recent registries, FM is associated with high rates of death and heart transplantation, regardless of the underlying histology. Because of a paucity of evidence-based management strategies exists for this disease, an International workshop on FM was held in Wuhan, China, in October 2019, in order to share knowledge on the disease and identify areas of consensus. The present report highlights both agreements and controversies in FM management across the world, focusing the attention on areas of opportunity, FM definition, the use of endomyocardial biopsy and viral identification on heart specimens, treatment algorithms including immunosuppression and the timing of circulatory support escalation. This report incorporates the most recent recommendations from national and international professional societies. Main areas of interest and aims of future prospective observational registries and randomized controlled trials were finally identified and suggested.

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

Int J Cardiol: 31 Jan 2021; 324:131-138
Veronese G, Ammirati E, Chen C, Klingel K, ... Cooper LT, Wang DW
Int J Cardiol: 31 Jan 2021; 324:131-138 | PMID: 33122017
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Impact:
Abstract

Infective endocarditis in patients after percutaneous pulmonary valve implantation with the stent-mounted bovine jugular vein valve: Clinical experience and evaluation of the modified Duke criteria.

Bos D, De Wolf D, Cools B, Eyskens B, ... Gewillig M, Heying R
Aims
Percutaneous pulmonary valve implantation (PPVI) has proven good hemodynamic results. As infective endocarditis (IE) remains a potential complication with limited available clinical data, we reviewed our patient records to improve future strategies of IE prevention, diagnosis and treatment.
Methods
Medical records of all patients diagnosed with Melody® valve IE according to the modified Duke criteria were retrospectively analyzed in three Belgian tertiary centers.
Results
23 IE episodes in 22 out of 240 patients were identified (incidence 2.4% / patient year) with a clear male predominance (86%). Median age at IE was 17.9 years (range 8.2-45.9 years) and median time from PPVI to IE was 2.4 years (range 0.7-8 years). Streptococcal species caused 10 infections (43%), followed by Staphylococcus aureus (n = 5, 22%). In 13/23 IE episodes a possible entry-point was identified (57%). IE was classified as definite in 15 (65%) and as possible in 8 (35%) cases due to limitations of imaging. Echocardiography visualized vegetations in only 10 patients. PET-CT showed positive FDG signals in 5/7 patients (71%) and intracardiac echocardiography a vegetation in 1/1 patient (100%). Eleven cases (48%) had a hemodynamically relevant pulmonary stenosis at IE presentation. Nine early and 6 late percutaneous or surgical re-interventions were performed. No IE related deaths occurred.
Conclusions
IE after Melody® valve PPVI is associated with a relevant need of re-interventions. Communication to patients and physicians about risk factors is essential in prevention. The modified Duke criteria underperformed in diagnosing definite IE, but inclusion of new imaging modalities might improve diagnostic performance.

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

Int J Cardiol: 14 Jan 2021; 323:40-46
Bos D, De Wolf D, Cools B, Eyskens B, ... Gewillig M, Heying R
Int J Cardiol: 14 Jan 2021; 323:40-46 | PMID: 32860844
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Impact:
Abstract

Disproportionate functional mitral regurgitation predicts a favourable response after MitraClip implant in patients with advanced heart failure. Real-world evidence of a new conceptual framework.

Frea S, Pidello Md S, Boretto Md P, Rettegno Md S, ... Rinaldi M, De Ferrari GM
Introduction
Accurate predictors of good clinical response after MitraClip implant in patients with heart failure (HF) are still lacking. Aim of this study was to investigate the role of regurgitant fraction >50% as a marker of disproportionate functional mitral regurgitation (FMR) in identifying best responders to Mitraclip.
Methods and results
Data from 58 advanced HF patients (age 66 ± 8 years, 81% males, 63% NYHA class IV, LV ejection fraction (EF) 25.5 ± 5.5%) with disproportionate and proportionate FMR who underwent successful MitraClip implant were analyzed. After MitraClip all patient achieved mild (≤ 2+/4+) MR. During 12-month follow-up 18 patients (31%) had a major adverse cardiac event (MACE, i.e. cardiac death, urgent LVAD implant or heart transplantation, HF hospitalization). Disproportionate FMR (n = 48, 83%) was associated with a better clinical outcome (p = .003) while regurgitant volume and EROA were not. TAPSE ≤14 mm was associated with worse outcome (p = .018). At multivariable analysis only disproportionate MR and TAPSE ≤14 mm showed a significant association with MACE (p = .017 and p = .02, respectively). A reverse left ventricular remodeling (i.e., reduction on LV end-diastolic diameter and end-diastolic volume) was achieved only in the disproportionate FMR group.
Conclusions
In conclusion, disproportionate FMR assessed by regurgitant fraction and RV dysfunction assessed by TAPSE may help the selection of HF patients candidates for MitraClip therapy.

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

Int J Cardiol: 14 Jan 2021; 323:208-212
Frea S, Pidello Md S, Boretto Md P, Rettegno Md S, ... Rinaldi M, De Ferrari GM
Int J Cardiol: 14 Jan 2021; 323:208-212 | PMID: 32795480
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Impact:
Abstract

Adherence to dabigatran and the influence of dabigatran-induced gastrointestinal discomfort in the real-world practice.

Hwang J, Lee SR, Park HS, Lee YS, ... Choi EK, Han S
Background
Dabigatran-induced gastrointestinal discomfort (DGID) is an important factor influencing the adherence to dabigatran. We investigated the incidence and risk factors of DGID and its impact on the adherence and persistence to dabigatran.
Methods
We prospectively enrolled the patients prescribed with dabigatran in 10 tertiary hospitals of the South Korea. The adherence was assessed using the percentage of the prescribed doses of the medication presumably taken by the patient (PDT by pill count). We evaluated the relationship between DGID and the baseline GI symptoms or the previous GI disease history using a questionnaire.
Results
A total of 474 patients (mean age 67.8 ± 9.3 years, male 68.6%, and mean CHADS-VASc score 2.2 ± 1.2) were enrolled. The adherence assessed by the PDT was 93.5 ± 5.5% at 1-month and 96.4 ± 8.4% at 6-months among the persistent patients. During the 6-month follow-up, 82 (18.1%) patients discontinued dabigatran, and the most common reason for dabigatran discontinuation was DGID (49, 59.8%). Sixty-eight (14.3%) patients experienced DGID, and there was no difference in the clinical factors between those with or without DGID. Among the patients who experienced DGID, 42 discontinued dabigatran (61.8%). In a multivariate analysis, DGID was the only predictor of dabigatran discontinuation and a low adherence.
Conclusion
Overall adherence of dabigatran was excellent, but those with DGID showed low adherence and persistence. Furthermore, it was challenging to predict DGID by clinical parameters. Therefore, it is recommended to follow the patients closely to check for DGID when prescribing dabigatran.

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

Int J Cardiol: 14 Jan 2021; 323:77-82
Hwang J, Lee SR, Park HS, Lee YS, ... Choi EK, Han S
Int J Cardiol: 14 Jan 2021; 323:77-82 | PMID: 32805331
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Impact:
Abstract

Cardiac mortality, diabetes mellitus, and multivessel disease in ST elevation myocardial infarction.

Burgess S, Juergens CP, Yang W, Shugman IM, ... Lo S, French J
Background
In patients with diabetes mellitus presenting with ST elevation myocardial infarction (STEMI) the degree to which cardiac death rates may be attributed to an increased burden of coronary artery disease is not clear.
Methods
This prospective observational study examines rates of cardiac death between those with and without diabetes at long term follow up, stratified by presence of multivessel disease (MVD), in consecutive STEMI patients from 5 Australian hospitals.
Results
Amongst 2083 patients, 393 patients had diabetes (18.8%), and 810 (38.8%) had MVD. Patients with diabetes were more likely to have MVD 48.6% (191/393) than patients without diabetes 36.6% (619/1690; p < .001). At final follow up (median 3.6 years [IQR 2.4-5.4]) cardiac death occurred in 37/393 diabetic patients and 92/1690 nondiabetic patients (adjusted HR1.67, 95% CI 1.10-2.52). In those with MVD cardiac death occurred in 27/191 diabetic patients, and 54/619 non-diabetic patients (adjusted HR 1.94; 95% CI 1.17-3.23). In single vessel disease (SVD) cardiac death occurred in 10/202 diabetic patients, and 38/1071 non-diabetic patients (adjusted HR 1.37; 95% CI 0.65-2.89). Both diabetes and MVD were independently associated with cardiac death.
Conclusions
STEMI patients with diabetes are more likely to have MVD, with an absolute difference in MVD rates of 12%, and higher rates of cardiac death. Randomized trials studying these high risk patients are needed to reduce cardiac mortality in patients with diabetes, MVD and STEMI.

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

Int J Cardiol: 14 Jan 2021; 323:13-18
Burgess S, Juergens CP, Yang W, Shugman IM, ... Lo S, French J
Int J Cardiol: 14 Jan 2021; 323:13-18 | PMID: 32805324
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Impact:
Abstract

Women\'s perspective on the COVID-19 pandemic: Walking into a post-peak phase.

Sabatino J, Moscatelli S, Rustamova Y, Kotlar I, ... Kemaloğlu Öz T,

The pandemic of Novel Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has provoked hundreds of thousands of deaths, resulting in catastrophe for humans. Although some insights have been garnered in studies on women, children and young adults infected with COVID-19, these often remain fragmented in literature. Therefore, we discussed the impact of COVID-19 pandemic on women, children and young patients, particularly those with underlying cardiovascular comorbidities or congenital heart disease. Furthermore, we gathered and distilled the existing body of literature that describes their cardiovascular complications and the recommended actions in favour of those patients toward the post-peak pandemic period. Although many questions still require answers, this article is sought to help the practicing clinician in the understanding and management of the threatening disease in special populations.

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

Int J Cardiol: 14 Jan 2021; 323:29-33
Sabatino J, Moscatelli S, Rustamova Y, Kotlar I, ... Kemaloğlu Öz T,
Int J Cardiol: 14 Jan 2021; 323:29-33 | PMID: 32800917
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Impact:
Abstract

Cardiotoxic mechanisms of cancer immunotherapy - A systematic review.

Lobenwein D, Kocher F, Dobner S, Gollmann-Tepeköylü C, Holfeld J

Cancer immunotherapy is a success story of translational medicine that has led to improved survival in patients with different difficult-to-treat types of cancer, such as metastasized melanoma, non-small cell lung cancer or renal cell carcinoma. These novel therapeutic agents exert their antitumor effects by activating the patients\' immune system against cancer cells. Immunotherapy can be divided into active agents, such as anti-tumour vaccines or adoptive T-cell transfer, and passive immunotherapies like monoclonal antibodies, checkpoint inhibitors, cytokine therapy, bispecific T-cell engagers. After initial experimental use, broad clinical application revealed a number of important cardiovascular side effects of immunotherapeutics, which limit treatment options and decrease patients\' prognosis and quality of life. With the rising rate of new immunotherapeutics at a hand, the number of patients receiving cancer immunotherapy will constantly increase, resulting in improved long-term survival rates. This review aims to summarize available cancer immunotherapies, their mechanism of action, currently known cardiovascular toxicities and their treatment. Further optimization of patient care will depend on the combined efforts by oncologists, cardiologists and cardiac surgeons to identify patients at risk and the implementation of interdisciplinary screening and treatment strategies. It is therefore crucial to familiarize heart specialists with novel cancer therapeutics and their potential adverse effects.

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2021; 323:179-187
Lobenwein D, Kocher F, Dobner S, Gollmann-Tepeköylü C, Holfeld J
Int J Cardiol: 14 Jan 2021; 323:179-187 | PMID: 32800915
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Impact:
Abstract

Cognitive impairment in patients with atrial fibrillation: Implications for outcome in a cohort study.

Malavasi VL, Zoccali C, Brandi MC, Micali G, ... Freedman B, Boriani G
Background
The impact of cognitive status on outcomes of patients with atrial fibrillation (AF) is not well defined.
Aims
To assess the prevalence of cognitive impairment in AF patients and evaluate its association with: i) all-cause mortality; ii) a composite endpoint of death, stroke/systemic embolism, hemorrhages, acute coronary syndrome, pulmonary embolism, new/worsening heart failure.
Methods
In a cohort study, cognitive status was assessed at baseline by the Mini Mental State examination adjusted for age and education (aMMSE). aMMSE <24 was considered indicative of cognitive impairment.
Results
The cohort included 437 patients (61.3% male, mean age 73.4 ± 11.7 years). Sixty-three patients (14.4%) had cognitive impairment at baseline aMMSE. Permanent AF (odds ratio [OR] 1.750; 95%CI 1.012-3.025; p = .045), haemoglobin levels (OR 0.827; 95%CI 0.707-0.967; p = .017) and previous treatment with antiplatelet drugs only, without oral anticoagulation, (OR 4.352; 95%CI 1.583-11.963; p = .004) were independently associated with cognitive impairment at baseline. After a median follow-up of 887 days (interquartile range 731-958) 30 patients died (7.1%), and 97 (22.9%) reached the composite endpoint. After adjustment for Elixhauser Comorbidy Measure, aMMSE <24 was significantly associated with all-cause mortality (hazard ratio [HR] 2.473, 95%CI 1.062-5.756, p = .036) and with the composite endpoint (HR 1.852, 95%CI 1.106-3.102, p = .019).
Conclusions
In patients with AF, cognitive impairment (aMMSE <24) is associated with worse outcomes, and the association of adverse outcomes with previous treatment with antiplatelet drugs only, without oral anticoagulation, highlights the potential role of appropriate antithrombotic treatment for improving patient prognosis.

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2021; 323:83-89
Malavasi VL, Zoccali C, Brandi MC, Micali G, ... Freedman B, Boriani G
Int J Cardiol: 14 Jan 2021; 323:83-89 | PMID: 32800908
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Impact:
Abstract

CHADS-VASc and readmission with new-onset atrial fibrillation, atrial flutter, or acute cerebrovascular accident.

Rutland J, Ayoub K, Etaee F, Ogunbayo G, ... Masri A, Elayi CS
Background
Although risk factors for atrial fibrillation (AF) and atrial flutter (AFL) are known, identifying patients who will develop AF/AFL within the near future remains challenging. We sought to evaluate if the CHADS-VASc risk score (CVRS) can identify hospital readmissions with AF, AFL, or acute cerebrovascular accident (CVA) among hospitalized patients without prior history of AF/AFL.
Methods
Using the Nationwide Readmission Database, a study cohort included patients without prior AF/AFL or new diagnosis of AF/AFL at the index hospitalization from 2012 to 2014. Patients were stratified based on the CVRS into three groups: Low (CVRS ≤1), Intermediate (CVRS 2-5), and High (CVRS ≥6).The primary outcome of interest was 180-day readmission rate with a primary or secondary diagnosis of AF/AFL. Secondary outcomes of interest were acute CVA and 6-month mortality rate.
Results
A total of 17,820,640 patients were included in our study. Over a 6-month follow up duration from the index hospitalization, the overall re-admission rate for new onset atrial arrhythmias (AF/AFL) was 3.48% (n = 620,986), acute CVA 0.13% (n = 22,522), and all-cause mortality 0.31% (n = 55,632). When compared to other groups, patients with a higher CVRS were readmitted more frequently for AF/AFL [odds ratio (OR) 2.43; 95% confidence interval (CI) 2.41-2.45, P < .0001), acute CVA (OR 3.96; 95%CI 3.85-4.08, P < .0001), and all-cause mortality (OR 2.19; 95%CI 2.14-2.24, P < .0001).
Conclusion
In this large contemporary cohort, a CHADS2VA2SC score ≥ 6 identified patients without known prior atrial arrhythmias at an elevated risk of developing AF/AFL or acute CVA within 6 months of hospitalization.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Jan 2021; 323:72-76
Rutland J, Ayoub K, Etaee F, Ogunbayo G, ... Masri A, Elayi CS
Int J Cardiol: 14 Jan 2021; 323:72-76 | PMID: 32800906
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Impact:
Abstract

Impact of hypertension on left ventricular function in patients after anthracycline chemotherapy for malignant lymphoma.

Tanaka Y, Tanaka H, Hatazawa K, Yamashita K, ... Minami H, Hirata KI
Background
Hypertension is considered an important risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) as well as heart failure. However, the impact of hypertension and left ventricular (LV) hypertrophy (LVH), which is associated with hypertension, on LV function in patients treated with anthracycline chemotherapy for malignant lymphoma remains uncertain.
Method
We studied 92 patients with malignant lymphoma and with preserved LV ejection fraction (LVEF). Echocardiography was performed before and two-month after anthracycline chemotherapy. CTRCD was defined as the presence of an absolute decrease in LVEF ≥10% to a final value <53%. LVH was defined as concentric hypertrophy, which was determined as relative wall thickness ≥ 0.42 and LV mass index >95 g/m for females and > 115 g/m for males.
Results
Relative decrease in LVEF after anthracycline chemotherapy in patients with hypertension (n = 23) was significantly higher than that in patients without hypertension (n = 69) (-5.8% [-9.4, -1.3]) vs. (-1.1% [-4.1, 2.5]); P = .005). Moreover, the prevalence of CTRCD in patients with hypertension tended to be higher than in those without hypertension (17% vs. 5%, p = .09). A sequential logistic model for predicting CTRCD, based on baseline clinical variables including major clinical risk factors, was improved by the addition of the complication of hypertension (P = .049), and further improved by the addition of the presence of LVH (P = .023).
Conclusions
Hypertension, especially when complicated by LVH, was found to be associated with LV dysfunction after anthracycline chemotherapy in patients with malignant lymphoma and preserved LVEF. Watchful observation or early therapeutic intervention may thus be needed for such patients by the addition of the presence of LVH.

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

Int J Cardiol: 14 Jan 2021; 323:126-132
Tanaka Y, Tanaka H, Hatazawa K, Yamashita K, ... Minami H, Hirata KI
Int J Cardiol: 14 Jan 2021; 323:126-132 | PMID: 32800904
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Impact:
Abstract

Increased heart rate with sleep disordered breathing in hypertrophic cardiomyopathy.

Konecny T, Khoo M, Covassin N, Edelhofer P, ... Ommen SR, Somers VK
Background
Current guidelines recommend medications with rate control properties for symptomatic patients with hypertrophic cardiomyopathy (HCM) based on the rationale that lowering heart rate (HR) improves their symptoms. Whether sleep disordered breathing (SDB) is associated with increased HR in HCM patients is not known.
Method
We diagnosed uncontrolled SDB (oxygen desaturation index ≥5) in consecutive echocardiographically confirmed HCM patients seen at Mayo Clinic, Rochester, and analyzed their HR as recorded by a 24-h Holter monitor. We compared mean, minimum, maximum HR between those with vs without SDB. In a pilot subanalysis of HCM patients with SDB who also underwent subsequent diagnostic polysomnography (PSG), we analyzed RR interval changes coinciding with obstructive sleep apnea and hypopnea episodes.
Results
Of the 230 HCM patients included in this study (age 54 ± 16 years; 138 male; LVOT pressure gradient at rest 45 ± 39 mmHg), 115 (50%) patients had SDB. HCM patients with SDB were recorded to have higher mean HR (71 vs. 67 bpm; p = .002, adjusted p = .001), and this difference was most pronounced during night hours of 10 PM to 5 AM (61 vs. 67 bpm; p < .001). In the pilot analysis of the available PSG data, the release of obstructive sleep apneas and hypopneas coincided with fluctuation of HR.
Conclusions
SDB is independently associated with higher mean HR in patients with HCM, and this difference is most significant during sleep. Treatment of SDB, which is readily available, should be tested as a complementary modality to the currently recommended pharmacotherapy aimed at lowering HR in patients with symptomatic HCM.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Jan 2021; 323:155-160
Konecny T, Khoo M, Covassin N, Edelhofer P, ... Ommen SR, Somers VK
Int J Cardiol: 14 Jan 2021; 323:155-160 | PMID: 32798627
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Impact:
Abstract

The impact of transcatheter aortic valve implantation on arterial stiffness and wave reflections.

Terentes-Printzios D, Gardikioti V, Aznaouridis K, Latsios G, ... Tousoulis D, Vlachopoulos C
Background
The study of arterial properties in patients with aortic valve stenosis who undergo transcatheter aortic valve implantation (TAVI) remains challenging and results so far seem equivocal. We sought to investigate the acute and long-term effect of TAVI on arterial stiffness and wave reflections.
Methods
We enrolled 90 patients (mean age 80.2 ± 8.1 years, 50% males) with severe symptomatic aortic stenosis undergoing TAVI. Arterial stiffness was assessed by carotid-femoral and brachial-ankle pulse wave velocity (cfPWV and baPWV). Augmentation index corrected for heart rate ([email protected]), central pressures and subendocardial viability ratio (SEVR) were assessed with arterial tonometry. Measurements were conducted at baseline, after TAVI and at 1 year.
Results
Immediately after TAVI there was an increase in arterial stiffness (7.5 ± 1.5 m/s vs 8.4 ± 1.7 m/s, p = .001 for cfPWV and 1773 ± 459 vs 2383 ± 645 cm/s, p < .001 for baPWV) that was retained at 1 year (7.5 ± 1.5 m/s vs 8.7 ± 1.7 m/s, p < .001 and 1773 ± 459 cm/s vs 2286 ± 575, p < .001). Post-TAVI we also observed a decrease in [email protected] (32.2 ± 12.9% vs 27.9 ± 8.4%, p = .016) that was attenuated 1 year later (32.2 ± 12.9% vs 29.8 ± 9.1%, p = .38), and an increase in SEVR (131.2 ± 30.0% vs 148.4 ± 36.1%, p = .002), which remained improved at 1 year (131.2 ± 30.0% vs 146.0 ± 32.2%, p = .01).
Conclusions
After TAVI the arterial system exhibits an increase of stiffness in response to the acute relief of the obstruction, which is retained in the long term.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Jan 2021; 323:213-219
Terentes-Printzios D, Gardikioti V, Aznaouridis K, Latsios G, ... Tousoulis D, Vlachopoulos C
Int J Cardiol: 14 Jan 2021; 323:213-219 | PMID: 32798625
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Impact:
Abstract

Psychological and clinical characteristics of patients with spontaneous coronary artery dissection: A case-control study.

Smaardijk VR, Mommersteeg PMC, Kop WJ, Pellegrini D, van Geuns RJ, Maas AHEM
Background
The relative frequency of psychological factors in patients with spontaneous coronary artery dissection (SCAD) compared to patients with traditional atherosclerosis-related type 1 acute coronary syndrome (ACS) is unknown. This study examines whether psychological factors and emotional or physical precipitants are more common in SCAD patients versus atherosclerosis-related ACS patients.
Methods
Participants with SCAD were recruited from a Dutch SCAD database. Given the predominance of SCAD in women (>90%), only female patients were included. The age- and sex-matched atherosclerosis-related ACS group was identified from a registry database. Online questionnaires and medical records were used to investigate psychological factors and clinical information. Univariate and multivariate logistic regression models were used to examine differences between 172 SCAD patients and 76 ACS patients on emotional and physical precipitants prior to the event and psychological factors after the event.
Results
Patients with SCAD were more likely to experience an emotional precipitant in the 24 h prior to the event (56%), compared with the ACS group (39%) (OR = 1.98, 95%CI 1.14-3.44). Multivariate analyses showed that this association remained significant after adjustment for covariates (OR = 2.17, 95%CI 1.08-4.36). At an average of 3.2 years post-hospitalization for the SCAD or atherosclerosis-related ACS event, both patient groups had similar high levels of perceived stress (50% vs. 45%, p = .471) and fatigue (56% vs. 53%, p = .643).
Conclusions
This study shows that risk profiles for SCAD differ from traditional atherosclerosis-related ACS. Our findings may help health professionals to recognize SCAD and offer tailored rehabilitation and prevention programs.

Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2021; 323:1-6
Smaardijk VR, Mommersteeg PMC, Kop WJ, Pellegrini D, van Geuns RJ, Maas AHEM
Int J Cardiol: 14 Jan 2021; 323:1-6 | PMID: 32798624
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Impact:
Abstract

Association of renal insufficiency with treatments and outcomes in patients with acute coronary syndrome in China.

Peng Y, Du X, Li X, Ji J, ... Patel A,
Background
We aimed to analyze the association of estimated glomerular filtration rate (eGFR) levels of hospitalized patients with treatment decisions and clinical outcomes in Chinese patients with acute coronary syndrome (ACS).
Methods
This was a secondary analysis study from CPACS-2 Program which was a trial of a quality improvement intervention in China and recruited 15,141 patients from 75 hospitals between October 2007 and August 2010. All patients were divided into three groups by the eGFR level on admission. The primary outcomes were several key performance indicators (KPIs) reflecting the management of ACS and the secondary outcomes were clinical outcomes.
Results
A total of 14,437 ACS patients were enrolled in this analysis. Among patients with reduced eGFR levels, fewer patients received appropriate medical therapy (p for trend <0.001) and fewer high-risk patients received coronary angiography (p for trend <0.001) compared to patients with a normal eGFR. Furthermore, 436 cases of death, 357 cases of cardiac death, 686 cases of major adverse cardiovascular events, and 198 cases of major bleeding episodes were reported. Patients with a worse eGFR level had significantly higher rates of death (p for trend <0.001), cardiac death (p for trend <0.001), major adverse cardiovascular events (p for trend <0.001) and major bleeding episodes (p for trend <0.001).
Conclusion
Among Chinese ACS patients, those with renal insufficiency have a lower percentage of adherence to guideline-recommended treatments and worse clinical prognosis. Renal insufficiency is an important factor affecting guideline implementation in Chinese ACS patients.
Clinical trial registration
http://www.anzctr.org.au/default.aspx. Unique identifier: ACTRN12609000491268.

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

Int J Cardiol: 14 Jan 2021; 323:7-12
Peng Y, Du X, Li X, Ji J, ... Patel A,
Int J Cardiol: 14 Jan 2021; 323:7-12 | PMID: 32810549
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Impact:
Abstract

The endocannabinoid 2-arachidonoylglycerol inhibits endothelial function and repair.

Jehle J, Eich L, Danisch M, Bagheri S, ... Lutz B, Nickenig G
Background
Endothelial dysfunction promotes atherogenesis, vascular inflammation, and thrombus formation. Reendothelialization after angioplasty is required in order to prevent stent failure. Previous studies have highlighted the role of 2-arachidonoylglycerol (2-AG) in murine experimental atherogenesis and in human coronary artery disease. However, the impact of 2-AG on endothelial repair and leukocyte-endothelial cell adhesion is still unknown.
Methods
Endothelial repair was studied in two treatment groups of wildtype mice following electrical injury of the common carotid artery. One group received the monoacylglycerol lipase (MAGL)-inhibitor JZL184, which impairs 2-AG degradation and thus causes elevated 2-AG levels, the other group received DMSO (vehicle). The effect of 2-AG on human coronary artery endothelial cell (HCAEC) viability, leukocyte-endothelial cell adhesion, surface expression of adhesion molecules, and expression of endothelial NO synthase (NOS3) was studied in vitro.
Results
Elevated 2-AG levels significantly impaired reendothelialization in wildtype mice following electrical injury of the common carotid artery. In vitro, 2-AG significantly reduced viability of HCAEC. Additionally, 2-AG promoted adhesion of THP-1 monocytes to HCAEC following pre-treatment of the HCAEC with 2-AG. Adhesion molecules (E-selectin, ICAM-1 and VCAM-1) remained unchanged in arterial endothelial cells, whereas 2-AG suppressed the expression of NOS3 in HCAEC.

Conclusion:
and translational aspect
Elevated 2-AG levels hamper endothelial repair and HCAEC proliferation, while simultaneously facilitating leukocyte-endothelial cell adhesion. Given that 2-AG is elevated in patients with coronary artery disease and non-ST-segment elevation myocardial infarction, 2-AG might decrease reendothelialization after angioplasty and thus impact the clinical outcomes.

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

Int J Cardiol: 14 Jan 2021; 323:243-250
Jehle J, Eich L, Danisch M, Bagheri S, ... Lutz B, Nickenig G
Int J Cardiol: 14 Jan 2021; 323:243-250 | PMID: 32810540
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Impact:
Abstract

Outcomes of ablation in Wolff-Parkinson-White-syndrome: Data from the German Ablation Registry.

Brado J, Hochadel M, Senges J, Kuck KH, ... Kääb S, Sinner MF
Aims
Catheter ablation is recommended for symptomatic WPW-syndrome. Commonly perceived low recurrence rates were challenged recently. We sought to identify patient strata at increased risk.
Method
Of 12,566 patients enrolled at 52 German Ablation Registry sites from 2007 to 2010, 789 were treated for WPW-syndrome. Patients were included for symptomatic palpitations and tachycardia documentation. Follow-up duration was one year. Overall complications were defined as serious, access-related, and ablation-related. We adjudicated WPW-recurrence for re-ablation during follow-up. Risk strata included: admission for repeat ablation at registry entry; accessory pathway localization; antiarrhythmic medical treatment before the ablation.
Results
WPW-syndrome patients were 42.8 ± 16.2 years on average; 39.9% were women. A majority of 95.9% was symptomatic; in 84.4%, a tachycardia was documented. Seventy-six (9.6%) patients presented for repeat procedures. Accessory pathways were located in the left atrium (71.4%), right atrium (21.1%), septum (4.4%), or coronary sinus diverticula (2.1%). Prior antiarrhythmic medication was used in 43.7% of patients. No serious events occurred. The overall complication rate was 2.5% (ablation related 1.2%, access-related 1.3%). Major determinants for complications were presentation for re-ablation as registry index procedure (6.9% vs 2.2%; p = 0.016) and septal pathway location (left 2.0% vs septal 9.1%, p = 0.014). The overall re-ablation rate was 9.7%. Usage of prior antiarrhythmic medication was associated with higher recurrence rates (12.2% vs. 7.6%; p = 0.035).
Conclusions
Patients at higher complication risk may be identified by repeat procedure and septal pathway location. Prior antiarrhythmic medication was associated with higher recurrence rates. Our findings may help improving peri-procedural patient management and information.

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

Int J Cardiol: 14 Jan 2021; 323:106-112
Brado J, Hochadel M, Senges J, Kuck KH, ... Kääb S, Sinner MF
Int J Cardiol: 14 Jan 2021; 323:106-112 | PMID: 32890614
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Impact:
Abstract

Oral anticoagulation and cardiovascular outcomes in patients with atrial fibrillation and chronic kidney disease in Asian Population, Data from the COOL-AF Thailand registry.

Chantrarat T, Krittayaphong R
Background:
and objectives
Patients with AF and chronic kidney disease(CKD) encountered increased risks of stroke, bleeding, morbidity, and overall mortality. Oral anticoagulation in these populations definitely enhances major bleeding but the benefit of stroke reduction remained inconclusive.The aim of this study is to evaluate the effect of oral anticoagulation (OAC) on the 2-year cardiovascular outcomes in patients with AF and CKD.
Method
NVAF patients were consecutively enrolled from 27 hospitals located all across Thailand.Baseline demographic and clinical data were collected within 6 months from enrollment.GFR was calculated using CKD-EPI formula. CKD patients were defined as GFR less than 60 mL/min/1.73 m according to KDOQI of the National Kidney Foundation. Clinical outcomes included ischemic stroke or transient ischemic attack (TIA) and major bleeding.
Results
At 25.7 ± 10.6 months of follow up, we identified 2538 patients with complete renal follow-up data. Among these were 1594 patients with CKD (stage 3-5) and 944 patients without CKD. The rate of ischemic stroke in patients with and without CKD were 3.7% and 1.7% respectively (p = 0.004),the rate of major bleeding was 5.6 and 3.5% accordingly (p = 0.015) and, likewise, the death rate was substantially high in patients with CKD (10.0% and 6.5%, p = 0.02). The rate of ischemic stroke/TIA in patients with CKD who were and were not on OAC did not differ significantly, 3.6% and 4.2% respectively (p = 0.602). NOAC and warfarin did not differ significantly in the propensity score-matched rate of both ischemic stroke/TIA (0 and 1.2%, p = 0.554) and major bleeding (3.3% and 7.4%, p = 0.122).The net clinical benefit of NOAC over warfarin was 2.153 per 100-patient years.
Conclusions
COOL AF registry demonstrated that AF patients with CKD had increased risks of ischemic stroke/TIA, major bleeding and death. The benefit of stroke/TIA reduction was not significantly evident for either warfarin or NOAC. However, NOAC was associated with the positive net clinical benefit over no OAC.

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

Int J Cardiol: 14 Jan 2021; 323:90-99
Chantrarat T, Krittayaphong R
Int J Cardiol: 14 Jan 2021; 323:90-99 | PMID: 32828960
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Impact:
Abstract

Angioedema with sacubitril/valsartan: Trial-level meta-analysis of over 14,000 patients and real-world evidence to date.

Dani SS, Ganatra S, Vaduganathan M
Background
Sacubitril/valsartan reduces the risk of hospitalizations and death among patients with heart failure (HF) with reduced ejection fraction; its use is poised to increase worldwide. As bradykinin is a substrate of neprilysin, angioedema was a theoretical concern potentiated by neprilysin inhibition.
Methods
We explored angioedema in clinical trials and real-world pharmacovigilance data. We conducted a trial-level random-effects meta-analysis of 5 RCTs studying the effects of sacubitril/valsartan in heart failure. FDA Adverse Event Reporting System (FAERS) provided real-world pharmacovigilance data in the US.
Results
The 5 trials enrolled 14,841 patients with follow-up ranging from 2 to 27 months. The collective rate of angioedema in RCTs was 0.5% in sacubitril/valsartan arms vs. 0.3% in control arms (pooled odds ratio of 1.35; 95% confidence interval - 0.45 to 4.1; P = .59) with moderate heterogeneity (I 55.2.%). These relative effects were driven by the larger PARADIGM-HF and PARAGON-HF experiences. FAERS pharmacovigilance data identified 426 angioedema cases over the last 5 years out of 40,559 adverse events reported related to sacubitril/valsartan.
Conclusions
Rates of angioedema with sacubitril/valsartan are reported to be low in RCTs and real-world clinical practice.

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

Int J Cardiol: 14 Jan 2021; 323:188-191
Dani SS, Ganatra S, Vaduganathan M
Int J Cardiol: 14 Jan 2021; 323:188-191 | PMID: 32841619
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Impact:
Abstract

Impact of sex on timing and clinical outcome of septal myectomy for obstructive hypertrophic cardiomyopathy.

Huurman R, Schinkel AFL, de Jong PL, van Slegtenhorst MA, Hirsch A, Michels M
Background
Sex disparities are common in hypertrophic cardiomyopathy (HCM). Previous research has shown that at time of myectomy, women are older, have greater impairment of diastolic function and more advanced cardiac remodeling. The clinical impact of these differences is unknown.
Method
This study included 162 HCM patients (61% men) who underwent septal myectomy. Time to treatment was calculated in relation to symptom onset and diagnosis. Pre- and post-operative echocardiographic data were collected. Sex differences were assessed at baseline and in time-to-event survival analyses for the composite endpoint of all-cause mortality, cardiac transplantation, re-intervention and aborted sudden cardiac death.
Results
Women were generally older at time of myectomy (57 vs. 49 years, p < 0.01), with similar time to treatment as measured from symptom onset (2.3 [1.3-6.0] vs. 2.8 [1.1-5.3] years, p > 0.05), but a shorter time since diagnosis compared to men (2.6 [1.2-7.0] vs. 4.3 [2.4-8.3] years, p = 0.02). Mean wall thickness and left atrial diameter were the same for men and women, but were higher in women when correcting for body surface area (absolute: 20 vs. 19 mm, 48 vs 46 mm, p ≥ 0.05; corrected: 9.7 vs. 11.2 mm/m, 23.4 vs. 26.3 mm/m, p < 0.01). After 5.9 [3.0-9.1] years, 15% of men and 8% of women had reached the composite endpoint (p > 0.05).
Conclusion
In conclusion, although women present later in life and seem to have more advanced disease on echocardiography, time until myectomy was similar and clinical outcomes after myectomy are favourable for both men and women.

Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2021; 323:133-139
Huurman R, Schinkel AFL, de Jong PL, van Slegtenhorst MA, Hirsch A, Michels M
Int J Cardiol: 14 Jan 2021; 323:133-139 | PMID: 32841616
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Impact:
Abstract

Atrial fibrillation in dilated cardiomyopathy: Outcome prediction from an observational registry.

Nuzzi V, Cannatà A, Manca P, Castrichini M, ... Boriani G, Sinagra G
Background
Little is known about the role of different types of atrial fibrillation (AF) in dilated cardiomyopathy (DCM). We investigated the epidemiological and prognostic impact of different types of AF in DCM during long-term follow-up.
Method
We evaluated consecutive DCM patients enrolled in the Trieste Muscle Heart Disease Registry. Uni- and multivariable, extended Kaplan-Meier and propensity score-matching analyses were performed for a composite outcome including death/heart transplantation/ventricular-assist device implantation.
Results
Out of 1181 DCM patients (71% males, age 49 ± 15 years, left ventricular ejection fraction 33 ± 11%), 46 (3.9%) had baseline permanent AF (permAF), while 66 (5.6%) had a history of paroxysmal/persistent AF. Compared with sinus rhythm (SR) patients, permAF patients were older (48 ± 15 vs. 61 ± 11 respectively, p = 0.001), were more frequently in NYHA class III-IV (18% vs. 30%, p = 0.002) and had larger left atrium diameter (40 ± 8 vs. 50 ± 10 mm, respectively). Paroxysmal/persistent AF patients had intermediate characteristics between permAF and SR. During a median follow-up of 135 (75-210) months, 63 patients developed permAF (0.45 new cases/100patients/year). At multivariable analysis, permAF as a time-dependent variable was an independent outcome predictor (HR 2.45; 95% C.I. 2.61-3.63, p < 0.001), together with creatinine, NYHA class, restrictive filling pattern and moderate-severe mitral regurgitation, while paroxysmal/persistent AF was neutral. Propensity score-matching analysis confirmed the higher rate of primary outcome events in patients with baseline or incident permAF versus patients without permAF during a very long-term follow-up (70% vs. 20%, p < 0.001).
Conclusions
PermAF in a large DCM cohort had low prevalence and incidence but had a relevant. prognostic role on hard outcomes.

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

Int J Cardiol: 14 Jan 2021; 323:140-147
Nuzzi V, Cannatà A, Manca P, Castrichini M, ... Boriani G, Sinagra G
Int J Cardiol: 14 Jan 2021; 323:140-147 | PMID: 32853666
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Impact:
Abstract

Catheterization laboratory activity before and during COVID-19 spread: A comparative analysis in Piedmont, Italy, by the Italian Society of Interventional Cardiology (GISE).

Quadri G, Rognoni A, Cerrato E, Baralis G, ... Tarantini G, Musumeci G
Background
COronaVIrus Disease 19 (COVID-19) led to the reorganization of Cardiology Units in terms of working spaces and healthcare personnel. In this scenario, both outpatient visits and elective interventional cardiology procedures were suspended and/or postponed. We aimed to report the impact of COVID-19 on interventional coronary and structural procedures in Piedmont, Italy.
Methods
The number of coronary angiographies (CAG), percutaneous coronary interventions (PCI), primary PCI (pPCI), transcatheter aortic valve replacements (TAVR) and Mitraclip performed in Piedmont between March 1st and April 20th, 2020 (CoV-time) were collected from each catheterization laboratory and compared to the number of procedures performed the year before in the same months (NoCoV-time).
Results
Procedural data from 18 catheterization laboratories were collected. Both coronary (5498 versus 2888: difference: -47.5%; mean 305.4 VS 160.4; p = 0.002) and structural (84 versus 17: difference: -79.8%; mean 4.7 Vs 0.9; p < 0.001) procedures decreased during CoV-time compared to NoCoV-time. In particular, coronary angiographies (1782 versus 3460), PCI (1074 versus 1983), p PCI (271 versus 410), TAVR (11 versus 72) and Mitraclip (6 versus 12) showed a reduction of 48.5%, 45.7%, 33.7%, 84.7% and 50.0%, respectively (all p for comparison <0.05).
Conclusions
Compared to the same time-period in 2019, both coronary and structural interventional procedures during COVID-19 epidemic suffered a dramatic decrease in Piedmont, Italy. Organizational change and structured clinical pathways should be created, together with awareness campaigns.

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

Int J Cardiol: 14 Jan 2021; 323:288-291
Quadri G, Rognoni A, Cerrato E, Baralis G, ... Tarantini G, Musumeci G
Int J Cardiol: 14 Jan 2021; 323:288-291 | PMID: 32858138
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Impact:
Abstract

Side-dependent effect in the response of valve endothelial cells to bidirectional shear stress.

Faure E, Bertrand E, Gasté A, Plaindoux E, Deplano V, Zaffran S

Endothelial cells covering the aortic and ventricular sides of the aortic valve leaflets are exposed to different stresses, in particular wall shear stress (WSS). Biomechanical stimuli actively regulate valve tissue structure and induce remodeling events leading to valve dysfunction. Endothelial to mesenchymal transformation (EndMT), for example, has been associated with aortic valve disease. The biomechanical response of cells at different sides of the leaflets has not been clearly characterized. To analyze the mechanical response of valve endothelial cells (VECs) we developed a unique fluid activation device that applies physiologically relevant pulsatile WSS. We characterized the morphology and function of adult porcine aortic VECs derived from the opposite sides of aortic valve leaflets following exposure to different pulsatile WSS. We found that elongation and orientation of cells in response to pulsatile WSS depends on their side of origin. Quantification of gene expression confirms phenotypic differences between aortic and ventricular VECs. Aortic VECs exposed to pulsatile WSS similar to that in vivo at the tip of aortic side of the valve leaflet upregulated pro-EndMT (ACTA2, Snail, TGFβ1) and inflammation (ICAM-1, VCAM-1) genes, whereas expression of endothelial markers like PECAM-1 was decreased. Conversely, ventricular-VECs showed strong increase of PECAM-1 expression and no activation of pro-EndMT marker. Finally, we found that stress-induced genes are upregulated in both cell types, at higher levels in ventricular compared to aortic VECs. Application of physiological shear stress levels using a fluid activation device therefore reveals functional differences in VECs derived from opposite sides of the aortic valve leaflets.

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

Int J Cardiol: 14 Jan 2021; 323:220-228
Faure E, Bertrand E, Gasté A, Plaindoux E, Deplano V, Zaffran S
Int J Cardiol: 14 Jan 2021; 323:220-228 | PMID: 32858136
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Abstract

Characteristics, prognosis and treatment response in distinct phenogroups of heart failure with preserved ejection fraction.

Gu J, Pan JA, Lin H, Zhang JF, Wang CQ
Background
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. We aimed to derive HFpEF phenotype-based groups based on clinical features using machine learning, and to compare clinical characteristics, outcomes and treatment response across the phenogroups.
Methods
We applied model-based clustering to 11 clinical and laboratory variables collected in 970 HFpEF patients. An additional 290 HFpEF patients was enrolled as a validation cohort. During 5-year follow-up, all-cause mortality was used as the primary endpoints, and composite endpoints (all-cause mortality or HF hospitalization) were set as the secondary endpoint.
Results
We identified three phenogroups, for which significant differences in the age and gender, the prevalence of concomitant ischaemic heart disease, atrial fibrillation and type 2 diabetes mellitus, the burden of B-type natriuretic peptide level and HF symptoms. Patients with phenogroup 3 had higher all-cause mortality or composite endpoints, whereas patients in phenogroup 1 had less adverse events after 5-year follow-up. Moreover, it was indicated that beta-blockers or angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) use was associated with a lower risk of all-cause mortality or composite endpoints in phenogroup 3, instead of the other phenogroups. This HFpEF phenogroup classification, including its ability to stratify risk, was successfully replicated in a prospective validation cohort.
Conclusion
Machine-learning based clustering strategy is used to identify three distinct phenogroups of HFpEF that are characterized by significant differences in comorbidity burden, underlying cardiac abnormalities, and long-term prognosis. Beta-blockers or ACEI/ARB therapy is associated with a lower risk of adverse events in specific phenogroup.

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

Int J Cardiol: 14 Jan 2021; 323:148-154
Gu J, Pan JA, Lin H, Zhang JF, Wang CQ
Int J Cardiol: 14 Jan 2021; 323:148-154 | PMID: 32860842
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Abstract

QTc interval in survivors of out of hospital cardiac arrest.

Anilkumar A, Moore EJ, Gall AJ, Sammut E, Barman P
Background
QTc interval (QTc) prolongation is seen on the post-arrest electrocardiogram (ECG) of many out of hospital cardiac arrest (OHCA) survivors. It remains unclear whether this is a transient phenomenon or a manifestation of an underlying arrhythmic substrate. This observational study assessed the trend of QTc in an unselected group of patients presenting with OHCA. We sought to identify any relationship between QTc, gender and aetiology of arrest. We observed whether targeted temperature management (TTM) is associated with malignant arrhythmia.
Method
We analysed 60 patients presenting with OHCA to the Bristol Heart Institute during a 20-month period. We measured QTc on admission and assessed for persistence, development and resolution of prolongation at up to 5 time points post-OHCA. Aetiology of arrest was divided into coronary, non-coronary or primary arrhythmic to investigate for patterns in QTc behaviour.
Results
81.7% (49/60) of arrests were attributed to an acute coronary event. 55% (33/60) had QTc prolongation on admission, of which 79% resolved. There were no significant differences in QTc behaviour by aetiology. One patient presenting with a normal QTc, developed prolongation during admission and received a genetic diagnosis of Long QT Syndrome. TTM was employed in 57/60, with no increased incidence of malignant arrhythmia.
Conclusions
Prolonged QTc on admission does not imply a primary arrhythmic aetiology and resolves in the majority pre-discharge. However, an initial normal QTc post-OHCA does not preclude a diagnosis of Long QT syndrome, highlighting the importance of thorough investigations in these patients. TTM appears safe from a cardiac perspective.

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

Int J Cardiol: 14 Jan 2021; 323:118-123
Anilkumar A, Moore EJ, Gall AJ, Sammut E, Barman P
Int J Cardiol: 14 Jan 2021; 323:118-123 | PMID: 32871190
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Abstract

Comparison of transvenous vs subcutaneous defibrillator therapy in patients with cardiac arrhythmia syndromes and genetic cardiomyopathies.

Kuschyk J, Müller-Leisse J, Duncker D, Tülümen E, ... Veltmann C, Rudic B
Background
Inherited arrhythmia syndromes and genetic cardiomyopathies attribute in a significant proportion to sudden cardiac death. Implantable cardioverter defibrillators (ICDs) are the cornerstone in the prevention of sudden death in high-risk patients. However, ICD therapy is also associated with high rates of inappropriate shocks and/or device-related complications especially in young patients.
Objective
To determine the outcome of high-risk patients with inherited arrhythmia syndromes and genetic cardiomyopathies comparing two defibrillator technologies.
Method
Between 2010 and 2018, 183 consecutive patients from two large German tertiary care centers were enrolled in the study. The majority of patients (83%) had either cardiac channelopathies or idiopathic ventricular fibrillation without cardiac structural abnormalities, while the remaining 17% had a genetic cardiomyopathy (HCM/ARVC). Eighty-six patients (47%) received a transvenous ICD (TV-ICD), while a subcutaneous ICD (S-ICD) was implanted in another 97 patients (53%).
Results
During a mean follow-up of 4.3 years, 30 patients had an appropriate ICD therapy (annual rate 3.8%). Fifteen patients experienced an inappropriate shock (annual rate 1.9%). Lead failure occurred in 17 (9%) patients and was less frequent in the S-ICD group (OR 0.48, 95%CI 0.38-0.62). Adverse defibrillator events, defined as a composite of inappropriate shocks and lead failure requiring surgical revision were significantly lower in the S-ICD group as compared to the TV-ICD group (OR 0.55, 95%CI 0.41-0.72). There was a non-significant trend towards lower appropriate shocks in the S-ICD group, that in combination with all-cause shocks yielded in a significantly higher freedom of any shock in the S-ICD group (RR 39%, p = 0.003). No deaths occurred during follow-up.
Conclusion
The present data favor the use of the subcutaneous ICD for patients with inherited arrhythmia syndromes and genetic cardiomyopathies who do not need anti-bradycardia pacing.

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

Int J Cardiol: 14 Jan 2021; 323:100-105
Kuschyk J, Müller-Leisse J, Duncker D, Tülümen E, ... Veltmann C, Rudic B
Int J Cardiol: 14 Jan 2021; 323:100-105 | PMID: 32871189
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Abstract

Impact of the T-wave characteristics on distinguishing arrhythmogenic right ventricular cardiomyopathy from healthy children.

Imamura T, Sumitomo N, Muraji S, Yasuda K, ... Makiyama T, Yoshinaga M
Background
T-wave inversion (TWI) is not considered useful for diagnosing pediatric arrhythmogenic right ventricular cardiomyopathy (ARVC), because right precordial TWI in ARVC resembles a normal juvenile pattern.
Objectives
The aims of this study were to clarify the electrocardiographic (ECG) characteristics of pediatric ARVC to distinguish those patients from healthy children.
Methods
Between 1979 and 2017, 11 ARVC patients under 18 years old were registered and compared with school screening ECGs from 48,401 healthy children.
Results
The mean age at the first arrhythmic event or diagnosis was 13.3 ± 4.7 years. Nine patients were asymptomatic initially and were found by ECG screening, but 6 developed severe symptoms during the follow-up. Healthy children had a normal juvenile pattern, while ARVC children, especially symptomatic patients, had a significant tendency to have inferior and anterior TWI. The phenomenon of T-wave discontinuity (TWD) in which the TWI became deeper from V1 to V3 and suddenly turned positive in V5 was significantly more frequent in ARVC (60%) than healthy children (0.55%). Anterior TWI and TWD were also significantly more frequent in those who developed severe symptoms. The sensitivity and specificity of TWD were 60% (95% CI, 31-83%), and 99% (95% CI, 99-99%) to distinguish ARVC from healthy children, as well as 100% (95% CI, 71-100%) and 80% (95% CI, 51-80%), respectively, to predict severe symptoms in the future.
Conclusions
The ECG is useful to distinguish ARVC children, even in the early phase. Anterior TWI and TWD could detect ARVC children and to predict the possible serious conditions.

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

Int J Cardiol: 14 Jan 2021; 323:168-174
Imamura T, Sumitomo N, Muraji S, Yasuda K, ... Makiyama T, Yoshinaga M
Int J Cardiol: 14 Jan 2021; 323:168-174 | PMID: 32877757
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Abstract

Multimodal assessment of vascular and ventricular function in children and adults with repaired aortic coarctation.

Weismann CG, Maretic A, Grell BS, Åkesson A, Hlebowicz J, Liuba P
Background
Coarctation of the Aorta (CoA) is associated with increased aortic stiffness and diastolic left ventricular dysfunction. The mechanisms involved and impact of age remain unclear. It was the aim of this study to characterize arterial and cardiac function, their correlation, and the effect of age in children and adults with repaired CoA.
Methods
Multimodal cardiovascular assessment from the ascending aorta to microcirculation and endothelial function was performed prospectively. Statistical analyses included multivariable linear regression and correlation of vascular parameters with age and diastolic function.
Results
Fifty-seven patients with well-repaired CoA and 77 healthy controls were included (age 8-59). There was no significant difference in age, gender, body surface area and BMI between the groups. Ascending aortic distensibility was decreased while common carotid intima media thickness, central augmentation index corrected to a heart rate of 75/min [Aix75], peripheral Aix75 and aging index were increased in the CoA group. Interestingly, in a subgroup analysis of CoA patients with tricuspid vs. bicuspid aortic valves (BAV), only the latter had increased Aix75. Carotid-femoral pulse wave velocity [cfPWV], reactive hyperemia index and microcirculation were not significantly different between CoA and control patients. Diastolic function was impaired in the CoA group relative to controls. Both diastolic function and age correlated moderate-strongly with arterial parameters.
Conclusions
Patients with well repaired CoA have increased proximal arterial stiffness which correlates with diastolic function and age. Increased Aix75 may be attributed to a high prevalence of associated BAV. Neither cfPWV nor peripheral endothelial or microcirculatory function are impaired.

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

Int J Cardiol: 14 Jan 2021; 323:47-53
Weismann CG, Maretic A, Grell BS, Åkesson A, Hlebowicz J, Liuba P
Int J Cardiol: 14 Jan 2021; 323:47-53 | PMID: 32889020
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Abstract

Impact of COVID-19 lockdown on lifestyle adherence in stay-at-home patients with chronic coronary syndromes: Towards a time bomb.

Cransac-Miet A, Zeller M, Chagué F, Faure AS, ... Boulin M, Cottin Y
Background
We aimed to evaluate the impact of coronavirus disease 2019 (COVID-19)-related lockdown on adherence to lifestyle and drug regimens in stay-at-home chronic coronary syndromes patients living in urban and rural areas.
Methods
A cross-sectional population-based study was perfomed in patients with chronic coronary syndromes. A sample of 205 patients was randomly drawn from the RICO (Observatoire des infarctus de Côte d\'Or) cohort. Eight trained interviewers collected data by phone interview during week 16 (April 13 to April 19), i.e. 4 weeks after implementation of the French lockdown (start March 17, 2020).
Results
Among the 195 patients interviewed (of the 205, 3 had died, 1 declined, 6 lost), mean age was 65.5 ± 11.1 years. Only six patients (3%) reported drug discontinuation, mainly driven by media influence or family members. All 166 (85%) patients taking aspirin continued their prescribed daily intake. Lifestyle rules were less respected since almost half (45%) declared >25% reduction in physical activity, 26% of smokers increased their tobacco consumption by >25%, and 24% of patients increased their body weight > 2 kg. The decrease in physical activity and the increase in smoking were significantly greater in urban patients (P < .05).
Conclusions
The COVID-19-related lockdown had a negative impact on lifestyle in a representative sample of stay-at-home CCS patients.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Jan 2021; 323:285-287
Cransac-Miet A, Zeller M, Chagué F, Faure AS, ... Boulin M, Cottin Y
Int J Cardiol: 14 Jan 2021; 323:285-287 | PMID: 32889019
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Abstract

Heart failure with preserved ejection fraction or non-cardiac dyspnea in paroxysmal atrial fibrillation: The role of left atrial strain.

Katbeh A, De Potter T, Geelen P, Di Gioia G, ... Van Camp G, Penicka M
Background
Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular (LV) filling pressures and left atrial (LA) phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce.
Objective
To assess relationship between the LAS and the probability of HFpEF in patients with dyspnea and paroxysmal AF.
Methods
The study included 205 consecutive patients (62 ± 10 years, 58% males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%), who underwent speckle tracking echocardiography during sinus rhythm. Probability of HFpEF was estimated using HFPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides.
Results
Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e\', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p < 0.05). All components of LAS and LA strain rate showed proportional impairment with increasing probability of HFpEF (all p < 0.05). Out of the speckle tracking-derived parameters, reservoir LAS showed the largest area under the curve (AUC = 0.78, p < 0.001) and the strongest independent predictive value (OR: 1.22, 95% CI 1.08-1.38) to identify patients with high probability of HFpEF.
Conclusions
Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

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

Int J Cardiol: 14 Jan 2021; 323:161-167
Katbeh A, De Potter T, Geelen P, Di Gioia G, ... Van Camp G, Penicka M
Int J Cardiol: 14 Jan 2021; 323:161-167 | PMID: 32882295
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Abstract

Left ventricular strain and fibrosis in adults with repaired tetralogy of Fallot: A case-control study.

de Alba CG, Khan A, Woods P, Broberg CS
Background
Left ventricular (LV) systolic dysfunction and myocardial fibrosis have prognostic implications in repaired tetralogy of Fallot (rTOF), but their relationship with myocardial strain is not well understood. We evaluated systolic strain and fibrosis (extracellular volume fraction, ECV) of the left ventricle (LV) using feature tracking with magnetic resonance and determine their association with each other and clinical outcome.
Method
Adults with rTOF and age-matched controls underwent CMR to measure LV-ECV. Feature-tracking was used to quantify radial, circumferential, and longitudinal strain in both 2 and 3 dimensions. Clinical events (death, arrhythmia and heart-failure hospitalization) were obtained through chart review. Associations between strain, ECV and clinical events were explored.
Results
48 rTOF subjects (age 40.5 ± 14.3, 42% female) and 20 healthy controls were included. Both LV 2D and 3D global circumferential strain (GCS) and global longitudinal strain (GLS) were lower in rTOF subjects (p ≤0.01 for all). There was no association between strain and LV-ECV. Strain parameters correlated with ventricular volumes and function. After a median follow-up of 8.5 years (range 1-10.9 years) there were 5 deaths, 6 hospitalizations and 9 new arrhythmias. By multivariate Cox-regression, GLS was an independent predictor of both hospitalization and death, whereas LV-ECV was an independent predictor of arrhythmia.
Conclusion
While both LV strain abnormalities and fibrosis are present in rTOF, they are associated with different types of clinical outcome, and not to each other. The findings suggest that these measures reflect different long-term adverse adaptations to abnormal hemodynamics.

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

Int J Cardiol: 14 Jan 2021; 323:34-39
de Alba CG, Khan A, Woods P, Broberg CS
Int J Cardiol: 14 Jan 2021; 323:34-39 | PMID: 32882293
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Abstract

The effect of tropomyosin variants on cardiomyocyte function and structure that underlie different clinical cardiomyopathy phenotypes.

Dorsch LM, Kuster DWD, Jongbloed JDH, Boven LG, ... Brundel BJJM, van der Zwaag PA


Background:
- Variants within the alpha-tropomyosin gene (TPM1) cause dominantly inherited cardiomyopathies, including dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathy. Here we investigated whether TPM1 variants observed in DCM and HCM patients affect cardiomyocyte physiology differently. Methods - We identified a large family with DCM carrying a recently identified TPM1 gene variant (T201M) and a child with RCM with compound heterozygote TPM1 variants (E62Q and M281T) whose family members carrying single variants show diastolic dysfunction and HCM. The effects of TPM1 variants (T201M, E62Q or M281T) and of a plasmid containing both the E62Q and M281T variants on single-cell Ca transients (CaT) in HL-1 cardiomyocytes were studied. To define toxic threshold levels, we performed dose-dependent transfection of TPM1 variants. In addition, cardiomyocyte structure was studied in human cardiac biopsies with TPM1 variants. Results - Overexpression of TPM1 variants led to time-dependent progressive deterioration of CaT, with the smallest effect seen for E62Q and larger and similar effects seen for the T201M and M281T variants. Overexpression of E62Q/M281T did not exacerbate the effects seen with overexpression of a single TPM1 variant. T201M (DCM) replaced endogenous tropomyosin dose-dependently, while M281T (HCM) did not. Human cardiac biopsies with TPM1 variants revealed loss of sarcomeric structures.
Conclusion:
- All TPM1 variants result in reduced cardiomyocyte CaT amplitudes and loss of sarcomeric structures. These effects may underlie pathophysiology of different cardiomyopathy phenotypes.

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2021; 323:251-258
Dorsch LM, Kuster DWD, Jongbloed JDH, Boven LG, ... Brundel BJJM, van der Zwaag PA
Int J Cardiol: 14 Jan 2021; 323:251-258 | PMID: 32882290
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Abstract

Assessment of injury current during leadless pacemaker implantation.

Breitenstein A, Saguner AM, Gasperetti A, Hofer D, ... Regoli F, Steffel J
Background
Leadless pacemakers are an established treatment option for bradyarrhythmias. Similar to conventional transvenous pacemakers, satisfying pacing values during implantation are targeted for optimal long-term device function. The objective is to investigate the role of a local injury current (IC) in leadless pacemaker implantations.
Method
The IC, sensing value, capture threshold and impedance were collected in 30 consecutive patients receiving a leadless pacemaker.
Results
39 EGMs were recorded from 30 patients (including 9 device repositions). An IC was detected in 15 cases (38%). At implantation, the presence of an IC was associated with a significantly lower sensing (7.1 ± 3.7 mV vs 12.0 ± 4.0 mV; P = 0.004) and a higher capture threshold (median threshold 1.13 V at 0.24 ms [0.50-2.00] vs 0.50 V at 0.24 ms [0.25-0.75]; P = 0.002) and with a 26 fold higher likelihood of device repositioning compared to the absence of an IC (OR 26.3 [2.79-248], P < 0.001). Patients with an IC in their final implant position had a lower sensing (9.3 ± 4.4 mV vs 13.6 ± 4.7 mV at implantation, P = 0.04), while the initially similar capture threshold was lower after 24 h in the IC group. After 2 weeks, all parameters were similar between the two groups.
Conclusions
Our study shows that an IC can readily be observed during leadless pacemaker implantation associated with a lower sensing and a higher capture threshold at implantation but with similar to even better values during follow-up.

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

Int J Cardiol: 14 Jan 2021; 323:113-117
Breitenstein A, Saguner AM, Gasperetti A, Hofer D, ... Regoli F, Steffel J
Int J Cardiol: 14 Jan 2021; 323:113-117 | PMID: 32916226
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Abstract

Determinants of outcome in patients with heart failure with reduced ejection fraction & secondary mitral regurgitation.

Chasapi A, Karogiannis N, Zidros S, Patel K, Lloyd G, Bhattacharyya S
Background
The outcome of secondary mitral regurgitation (MR) in patients with heart failure is poor. Survival is related to the severity of MR. We sought to investigate the effect of left ventricular contractility, the ratio of left ventricular end-diastolic volume (LVEDV) to effective orifice area (EROA) and the ratio of regurgitant volume (RVol) to stroke volume (SV) on cardiovascular survival.
Methods
188 patients with a left ventricular ejection fraction (LVEF) < 50% and secondary MR were included. Groups were divided into tertiles. The Kaplan Meier method and log rank test were used to identify differences in survival between groups. Cox regression was used to identify independent predictors of cardiac mortality.
Results
Median follow-up was 30.4 months. Patients with a more abnormal global longitudinal strain (GLS) had lower survival, p = 0.001. There was no difference in survival between patients with an LVEF <30%, 30%-40% and >40%, p = 0.27. Patients with a higher RVol/SV ratio had lower survival than those with a lower ratio, p < 0.0001. Patients with a lower LVEDV/EROA ratio had worse survival than those with a higher ratio, p < 0.0001. Independent predictors of cardiovascular mortality were GLS (<5.6%) hazard ratio (HR) 2.7, the ratio of RVol/SV (>1.38) HR 4.96 and the ratio of LVDEV to EROA (<263) HR 4.49.
Conclusion
The main determinants of cardiovascular mortality in patients with secondary MR and heart failure are more abnormal GLS, lower LVEDV/EROA ratio and higher RVol/SV ratio. These may help risk stratify patients to help determine the optimal management strategy.

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

Int J Cardiol: 14 Jan 2021; 323:229-234
Chasapi A, Karogiannis N, Zidros S, Patel K, Lloyd G, Bhattacharyya S
Int J Cardiol: 14 Jan 2021; 323:229-234 | PMID: 32911003
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Impact:
Abstract

Oral anticoagulation and clinical outcomes in COVID-19: An Italian multicenter experience.

Schiavone M, Gasperetti A, Mancone M, Curnis A, ... Galli M, Forleo GB
Background
Since the body of evidence addressing the coagulation derangements caused by Coronavirus disease (COVID-19) has been constantly growing, we investigated whether pre-hospitalization oral anticoagulation (OAC) or in-hospital heparin treatment could have a protective role among COVID-19 patients.
Method
In this cohort study, consecutive COVID-19 patients admitted to four different Italian Institutions were enrolled. Baseline demographic, clinical, laboratory, and radiological characteristics, as well as in-hospital treatment and outcomes were evaluated. The primary outcome was mortality.
Results
A total of 844 COVID-19 patients were enrolled as study cohort, n = 65 (7.7%) taking OACs prior to hospitalization. Regarding clinical outcomes, OAC patients developed acute hypoxemic respiratory failure (AHRF) more frequently than non-OAC patients as well as presenting a higher mortality rate (44.6% vs 19.8%, p < 0.001). At overall multivariate logistical regression, use of heparin (n = 394, 46.6%) was associated with a better chance of survival to hospital discharge (OR 0.60 [0.38-0.94], p < 0.001), in particular in patients with AHRF, with no association found with the use of OACs. In a sub-analysis, the highest mortality rate was found for AHRF patients when heparin was not administered.
Conclusion
In our cohort, OACs appeared to be ineffective in reducing mortality rate, while heparin resulted to be a useful treatment when lung disease was sufficiently severe, potentially suggesting a crucial role of microthrombosis in severe COVID-19. Due to the relatively small number of COVID-19 patients treated with OACs included in our analysis and their higher number of comorbidities, larger studies are needed in order to confirm our findings.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Jan 2021; 323:276-280
Schiavone M, Gasperetti A, Mancone M, Curnis A, ... Galli M, Forleo GB
Int J Cardiol: 14 Jan 2021; 323:276-280 | PMID: 32911000
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Impact:
Abstract

Unusual arterial thrombotic events in Covid-19 patients.

de Roquetaillade C, Chousterman BG, Tomasoni D, Zeitouni M, ... Metra M, Mebazaa A
Introduction
COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. While several studies reported a high incidence of venous thromboembolic events. The occurrence of arterial thromboses are yet rarely described and could be underestimated.
Objectives
To describe the clinical and biological characteristics of COVID-19 patients presenting with an associated arterial thromboembolic event.
Material and methods
We performed a retrospective multicentric study in 3 centers between France and Italy. All patients with a confirmed SARS-CoV-2 infection and arterial thromboembolic events were included in the analysis.
Results
From March 8th to April 25th 2020, we identified 20 patients (24 events) with arterial thromboembolic events over 209 admitted patients (9.6%) with severe COVID-19 infection. Arterial thrombotic events included acute coronary occlusions (n = 9), stroke (n = 6), limb ischemia (n = 3), splenic infarcts (n = 3), aortic thrombosis (n = 2) and occlusive mesenteric ischemia (n = 1). At the time of the event, 10/20 (50%) of patients received thromboprohylaxis, 2/20 (10%) were receiving treatment dose anticoagulation and 5/20 (25%) were receiving antiplatelet therapy.
Conclusion
Our observations suggest that serious arterial thrombotic events might occur in Covid-19 patients. However, the exact incidence of such events and the best way to prevent them yet remains to be investigated.

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

Int J Cardiol: 14 Jan 2021; 323:281-284
de Roquetaillade C, Chousterman BG, Tomasoni D, Zeitouni M, ... Metra M, Mebazaa A
Int J Cardiol: 14 Jan 2021; 323:281-284 | PMID: 32918938
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Impact:
Abstract

Economic consequences of rheumatic heart disease: A scoping review.

Opara CC, Aghassibake N, Watkins DA
Background
Rheumatic heart disease (RHD) remains endemic in less-resourced regions and countries and results in high medical and non-medical costs to households, health systems, and society. This scoping review maps out the available evidence on the economic impact of RHD and its antecedents and suggests future research priorities.
Method
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. We identified articles through systematic electronic database search supplemented by expert knowledge of unpublished literature. Studies were included if they collected empirical RHD-related costing data as a primary or secondary objective and if the data were collected from 2000 onward. Main quantitative findings by intervention, costing perspective, and location were charted, and a standardized quality assessment tool was used to appraise included studies.
Results
The index search identified 2519 electronic records and two grey-literature graduate theses. Six full texts were included in the review. Primary prevention costs were modest, while secondary and especially tertiary prevention were more costly. Most estimates were of health sector costs and for tertiary interventions. Only two studies described RHD-related costs in non-high-income countries. Most studies were of adequate methodological quality.
Conclusion
Research into the costs of RHD has mostly been done in wealthy countries. Costs from the household perspective, which are particularly important in countries with limited public healthcare finance, are lacking. To inform advocacy and guide implementation of the 2018 World Health Assembly resolution on RHD, high-quality, local cost estimates will be needed from a range of representative, RHD-endemic countries.

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

Int J Cardiol: 14 Jan 2021; 323:235-241
Opara CC, Aghassibake N, Watkins DA
Int J Cardiol: 14 Jan 2021; 323:235-241 | PMID: 32920073
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Impact:
Abstract

Comparison of risk stratification models for pregnancy in congenital heart disease.

Denayer N, Troost E, Santens B, De Meester P, ... Budts W, Van De Bruaene A
Background
Pregnancy in women with congenital heart disease (CHD) is associated with increased risk for maternal cardiac complications. Several risk stratification models are used to predict adverse cardiac outcome in women with CHD who become pregnant. This study was set up as an exploratory study to provide a head-to-head comparison of the 4 most commonly used models: CARPREG, CARPREG II and ZAHARA risk scores and mWHO risk classification.
Methods and results
We randomly selected 100 women from the database of paediatric and congenital heart disease of the University Hospitals Leuven. Individual pregnancy risk scores were retrospectively calculated and summarized in a weighted average risk for each risk stratification model. To evaluate accuracy of each model, the weighted average risk was plotted against the actual observed number of \"cardiac events\" as defined in the respective risk models. Maternal adverse cardiac events occurred in 8% of our study population. Weighted average risks were plotted versus the observed number of events for each model: 10.1% versus 4.0% for CARPREG, 8.6% versus 5.0% for CARPREG II, 11.1% versus 8.0% for ZAHARA and 12.4% versus 8.0% for the mWHO classification.
Conclusion
All risk models overestimated maternal cardiac risk. The ZAHARA risk model appeared to be a closer reflection of maternal risk in our cohort of CHD patients. More research on a larger study population is needed.

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

Int J Cardiol: 14 Jan 2021; 323:54-60
Denayer N, Troost E, Santens B, De Meester P, ... Budts W, Van De Bruaene A
Int J Cardiol: 14 Jan 2021; 323:54-60 | PMID: 32931856
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Impact:
Abstract

A window into portal hemodynamics in adult fontan patients?

Simmons MA, Revzin M, To U, Liapakis A, Fahey J, Elder RW
Background
Fontan circulation alters portal venous hemodynamics, causing chronic passive hepatic congestion and fibrosis. This congestion increases liver stiffness (LS) leading to overestimates of liver fibrosis as measured by ultrasound shear wave elastography (SWE) of the liver. We evaluated whether Fontan circulation has a similar effect on spleen stiffness (SS) and SS/LS ratio as measured by SWE.
Methods
We retrospectively compared the SS of adult Fontan patients to age and gender matched, control patients without congenital heart disease. We correlated SS measurements to LS measurements and also performed a limited subgroup analysis of SS in Fontan patients with various manifestations of Fontan Associated Liver Disease.
Results
SS in Fontan patients was similar to healthy controls (1.43 vs. 1.36 m/s, p = 0.26). LS was elevated in 78% of the Fontan patients (mean 1.68 m/s, SD 0.31, 95% CI 1.53-1.85). The correlation between LS and SS was modest (Pearson\'s correlation coefficient, r = 0.5) but did not reach statistical significance (p = 0.06). The mean SS/LS ratio was 0.85 (95% CI 0.77-0.94).
Conclusion
Based on our study cohort, SS in Fontan patients is similar to age and gender matched control patients without congenital heart disease. The SS/LS ratio, however, is frequently less than 1, which is lower than that reported in both healthy patients and those with other forms of non-cardiac liver disease. SS and SS/LS ratio may be a useful indicator of portal hemodynamics in Fontan patients.

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

Int J Cardiol: 14 Jan 2021; 323:61-64
Simmons MA, Revzin M, To U, Liapakis A, Fahey J, Elder RW
Int J Cardiol: 14 Jan 2021; 323:61-64 | PMID: 32979426
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Impact:
Abstract

Abnormal aortic arch shape and vortical flow patterns are associated with descending aortic dilatation in patients with hypoplastic left heart syndrome.

Voges I, Scheewe J, Attmann T, Uebing A, Oechtering T, Gabbert D
Introduction
The descending aorta (DAo) in patients with hypoplastic left heart syndrome (HLHS) after Norwood procedure is frequenty enlarged and exhibits increased stiffness. Such findings of previous studies still remain unexplained given the fact that the DAo is not involved in the Norwood operation.
Methods
We studied five HLHS patients with DAo dilatation (aged: 2.9-15.1 years (y), median 9.0 y), four HLHS patients without DAo dilatation (aged: 3.5-9.7 years, median 6.45 y) and 7 healthy controls (aged 6.3-41.6 y, median 26.0 y) using cardiovascular magnetic resonance imaging with acquisition of cine images, contrast-enhanced angiograms and 4D flow. 4D flow data were analyzed based on in-house developed analysis software to quantify vortical flow patterns in terms of vorticity.
Results
All patients with DAo dilatation presented with a caliber reduction between the proximal and distal aortic arch of more than 40% (median reduction 71%, range 43%-79%) and with increased z-scores of the DAo. Vorticity in the DAo of patients with DAo dilatation (median: -24 s, range: -26 s - -8 s) was significantly increased in magnitude compared to controls (median: 0 s, range: -2 - +2) (p < 0.01). Vorticity in the DAo of patients without DAo dilatatation was not significantly increased compared to controls. DAo z-scores were associated with increased vorticity.
Conclusions
The findings of signficiantly increased vorticity and its association with increased DAo z-scores can potentially explain vascular alterations in the DAo of HLHS patients. This study gives motivation for further investigations and may ultimately lead to future Norwood procedure modifications.

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

Int J Cardiol: 14 Jan 2021; 323:65-67
Voges I, Scheewe J, Attmann T, Uebing A, Oechtering T, Gabbert D
Int J Cardiol: 14 Jan 2021; 323:65-67 | PMID: 32991943
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Impact:
Abstract

Extent of lung involvement over severity of cardiac disease for the prediction of adverse outcome in COVID-19 patients with cardiovascular disease.

Andreini D, Conte E, Mushtaq S, Gigante C, ... Assanelli E, Pepi M
Background
Aim of the present study was to assess if the presence of high cardiovascular risk, left ventricle systolic dysfunction or elevated BNP or Troponin are able to independently predict the outcome of patients with known cardiac disease and COVID-19 pneumonia.
Methods and results
From March 7th to April 28th, forty consecutive patients with known cardiac disease (chronic coronary artery disease, n=38; atrial fibrillation, n = 7; valvular disease, n = 13) referred to our emergency department for symptoms of suspected COVID-19, laboratory diagnosis of COVID-19 and typical signs of viral pneumonia at chest CT were enrolled in the study. The only predictor of the composite end-point (all cause of death + invasive ventilation + thromboembolic event) was the lung involvement % at chest CT (OR: 1.06; 95%CI: 1.01-1.11, P = 0.02). In the multivariate analysis, the lung involvement % at chest CT was the only independent predictor of the composite end-point (OR: 1.06; 95%CI: 1.01-1.11, P = 0.034).
Conclusions
The extent of lung involvement by COVID-19 is the only independent predictor of adverse outcome of patients and is predominant over the severity of cardiac disease.

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

Int J Cardiol: 14 Jan 2021; 323:292-294
Andreini D, Conte E, Mushtaq S, Gigante C, ... Assanelli E, Pepi M
Int J Cardiol: 14 Jan 2021; 323:292-294 | PMID: 33038410
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Impact:
Abstract

Long-term Follow-Up of Patients with Heart Failure and Reduced Ejection Fraction Receiving Autonomic Regulation Therapy in the ANTHEM-HF Pilot Study.

Sharma K, Premchand RK, Mittal S, Monteiro R, ... KenKnight BH, Anand IS
Background
The ANTHEM-HF pilot study was an open-label study that evaluated the safety and feasibility of autonomic regulation therapy (ART) utilizing cervical vagus nerve stimulation (VNS) for patients with chronic HF with reduced EF (HFrEF). Patients in NYHA class II-III with EF ≤40% (n = 60) received ART for 6 months post-titration. ART was associated with sustained improvement in left ventricular (LV) function and HF symptoms at 6 and 12 months.
Methods
Continuously cyclic VNS was maintained to determine longer-term safety and chronic effects of ART. Echocardiographic parameters and HF symptoms were assessed throughout a follow-up period of at least 42 months.
Results
Between 12 and 42 months after initial titration, there were no device-related SAEs or malfunctions. There were 10 SAEs adjudicated to be unrelated to VNS, including 5 deaths. There were 6 non-serious adverse events that were adjudicated to be device-related (2 oropharyngeal pain, 1 implant site pain, 2 voice alteration, and 1 hoarseness). At 42 months, there was significant improvement from baseline in LVEF, NYHA class, 6-min walk distance, and MLHFQ score. However, these improvements at 42 months were not significantly different from mean values at 6 and 12 months.
Conclusions
In a 42-month follow-up, ART was durable, safe, and was associated with beneficial effects on LVEF and 6-min walk distance. Long term, chronic, open-loop ART continued to be well-tolerated in patients with HFrEF. The open label, randomized, controlled, ANTHEM-HFrEF Pivotal Study is currently underway to further evaluate ART in patients with advanced HF.

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2021; 323:175-178
Sharma K, Premchand RK, Mittal S, Monteiro R, ... KenKnight BH, Anand IS
Int J Cardiol: 14 Jan 2021; 323:175-178 | PMID: 33038408
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Impact:
Abstract

Mid-term outcomes with adult endovascular treatment of coarctation of the aorta.

Nagendran J, Mathew A, Kang JJH, Bozso SJ, Hong Y, Taylor DA
Background
This study examines the contemporary medium- and long-term outcomes of endovascular repair of aortic coarctation in the adult.
Methods
We reviewed the clinical and imaging data of 56 consecutive adult patients with aortic coarctation who underwent endovascular repair at the Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada, from 2003 to 2018.
Results
There were 20 (35.7%) female and 36 (64.3%) male patients (including 9 re-intervention cases) with a mean age of 33.6 ± 13.6 years. Thirty-seven (66.1%) were treated with balloon-expandable covered stent and 12 (21.4%) were treated with balloon-expandable bare-metal stent. Pressure gradients decreased from baseline level of 27.99 ± 12.75 (8-70) mm Hg to 5.33 ± 4.42 (0-17.5) mm Hg following the procedure. There were 2 (3.6%) procedure related complications (aortic dissection [n = 1] and stent malposition [n = 1]). During a median (Q1 - Q3) follow up of 5.36 (2.28-7.58) years, 2 deaths (4.2%) and 9 (19%) re-interventions occurred, and the overall survival was 95.8%.
Conclusion
Percutaneous coarctoplasty, with either covered or bare metal stents, is a safe and durable option for aortic coarctation repair with excellent long-term survival.

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

Int J Cardiol: 14 Jan 2021; 323:267-270
Nagendran J, Mathew A, Kang JJH, Bozso SJ, Hong Y, Taylor DA
Int J Cardiol: 14 Jan 2021; 323:267-270 | PMID: 33148463
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Impact:
Abstract

Circulating growth factors and cardiac remodeling in the community: The Framingham Heart Study.

Castro-Diehl C, Song RJ, Sawyer DB, Wollert KC, ... Vasan RS, Xanthakis V
Background:
and aims
Cardiac and vascular growth factors (GF) may influence myocardial remodeling through cardiac growth and angiogenic effects. We hypothesized that concentrations of circulating GF are associated with cardiac remodeling traits.
Methods
We related blood concentrations of vascular endothelial GF (VEGF), VEGFR-1 (sFlt1), angiopoietin 2 (Ang-2), soluble angiopoietin type-2 receptor (sTie2), hepatocyte GF (HGF), insulin-like GF (IGF)-1, IGF binding protein (IGFBP)-3, and growth differentiation factor-15 (GDF-15) to echocardiographic traits in 3151 Framingham Study participants (mean age 40 years, 55% women). We evaluated the following measures: left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), global longitudinal strain (GLS), mitral E/e\', and aortic root diameter (AoR). All biomarker values were sex-standardized.
Results
In multivariable-adjusted analyses, higher GDF-15 concentrations were associated with higher log-LVMi (β = 0.009 per SD, P = 0.01). Similarly, sTie2 concentrations were positively associated with log-E/e\' (β = 0.011 per SD, P = 0.04). IGF-1 and Ang-2 concentrations were positively and negatively associated with GLS, respectively (β = 0.16 per SD and β = -0.15 per SD, both P < 0.05), whereas higher sFlt1 and Ang-2 levels were associated with smaller log-AoR (β = -0.004 per SD and β  = -0.005 per SD, respectively; P < 0.05).
Conclusion
In our large community-based sample, we observed patterns of associations between several circulating vascular GF and cardiac remodeling indices that are consistent with the known biological effects of these pro- and anti-angiogenic factors on the myocardium and conduit arteries. Additional studies are warranted to replicate our findings and assess their prognostic significance.

Copyright © 2021 Elsevier Ireland Ltd. All rights reserved.

Int J Cardiol: 06 Jan 2021; epub ahead of print
Castro-Diehl C, Song RJ, Sawyer DB, Wollert KC, ... Vasan RS, Xanthakis V
Int J Cardiol: 06 Jan 2021; epub ahead of print | PMID: 33422565
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Impact:
Abstract

Impact of History of Depression on 1-Year Outcomes in Patients with Chronic Coronary Syndromes: An Analysis of a Contemporary, Prospective, Nationwide Registry.

Luca , Temporelli PL, Amico AF, Gonzini L, ... Gabrielli D, Gulizia MM
Background
Depression is common in patients with acute cardiovascular conditions and it is associated with adverse clinical events.
Methods
Using the data from a nationwide, prospective registry on patients with chronic coronary syndromes (CCS), we assessed the impact of depression on major adverse cardiovascular events (MACE), a composite of all-cause death and hospitalization for myocardial infarction, revascularization, heart failure or stroke, and quality of life (QoL) at 1-year follow-up.
Results
From the 5070 consecutive CCS patients enrolled in the registry, 531 (10.5%) presented a history of depression and the remaining 4539 (89.5%) did not. At 1 year (median 369; IQR 362-378 days) from enrolment, the incidence of the primary composite outcome was 9.8% for patients with a history of depression and 7.2% for non-depressed patients (p = 0.03). Patients with history of depression had a significantly higher rate of all-cause mortality (3.0% vs 1.4%; p = 0.004) and hospital admission for heart failure (3.4% vs 1.3%; p = 0.0002) compared to the group without depression. However, history of depression did not result as an independent predictor of MACE at multivariable analysis [hazard ratio 1.17, 95% confidence interval (0.87-1.58), p = 0.31]. Depressed patients had worse QoL according to all domains of the EQ. 5D-5L questionnaire as compared to non-depressed patients (all p < 0.001), at both enrolment and follow-up.
Conclusions
In this contemporary, large cohort of consecutive patients with CCS, patients with a history of depression experienced a two-fold rate of mortality, a higher incidence of MACE and a worse QoL at 1-year follow-up, compared to non-depressed patients.

Copyright © 2021 Elsevier Ireland Ltd. All rights reserved.

Int J Cardiol: 06 Jan 2021; epub ahead of print
Luca , Temporelli PL, Amico AF, Gonzini L, ... Gabrielli D, Gulizia MM
Int J Cardiol: 06 Jan 2021; epub ahead of print | PMID: 33422564
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Impact:
Abstract

Polymorphisms in the IL-6 and TNF-α gene are associated with an increased risk of abdominal aortic aneurysm.

Jabłońska A, Zagrapan B, Neumayer C, Eilenberg W, ... Nanobachvili J, Huk I
Background
An abdominal aortic aneurysm (AAA) is a complex disease of the aging population that is associated with inflammation and the cellular immune response. To investigate the influence of interleukin (IL)-6 and tumor necrosis factor (TNF)-α single nucleotide polymorphisms (SNPs) on the risk of AAA formation and progression, the frequency of AAA and its associated risk factors were determined.
Method
Four SNPs in the IL-6 (-174G/C, rs1800795; -572G/C, rs1800796) and TNF-α (-238G/A, rs361525; -308G/A, rs1800629) genes were studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients with AAA and healthy volunteers. The mRNA expression and plasma IL-6 and TNF-α levels were also determined.
Results
A mutation detected in at least one allele of the IL-6 -174G/C SNP was associated with a 2-fold increased risk of AAA occurrence (OR: 2.08; 95% CI: 1.15-3.76; p = 0.014, in the dominant model). An increased risk of AAA incidence among heterozygous carriers of the TNF-α - 308G/A genotype was observed (OR: 2.06; 95% CI: 1.17-3.62; p = 0.011, in the overdominant model). The wild-type genotypes of the IL-6 -174G/C and the TNF-α -308G/A SNPs coexisted more frequently in healthy subjects than in AAA patients and was associated with decreased risk of AAA (p < 0.001). Moreover, elevated levels of IL-6 and TNF-α were associated with an increased risk of hypertension (p < 0.001 and p = 0.022, respectively).
Conclusions
The IL-6 -174G/C and the TNF-α -238G/A gene polymorphisms are associated with an increased risk of abdominal aortic aneurysm development.

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

Int J Cardiol: 05 Jan 2021; epub ahead of print
Jabłońska A, Zagrapan B, Neumayer C, Eilenberg W, ... Nanobachvili J, Huk I
Int J Cardiol: 05 Jan 2021; epub ahead of print | PMID: 33359288
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Impact:
Abstract

ApoA-I mimetic does not improve left ventricular diastolic dysfunction in rabbits without aortic valve stenosis.

Nachar W, Merlet N, Maafi F, Mihalache-Avram T, ... Rhéaume E, Tardif JC
Background
We previously demonstrated that high-density lipoprotein (HDL) infusions may improve left ventricular diastolic dysfunction (LVDD) in an aortic valve stenosis (AVS) model. Whether the benefit was direct or mediated by the observed reduction in AVS severity is not clear. Here, we aimed to test the direct effect of an ApoA-I mimetic on LVDD in the absence of AVS.
Methods
Rabbits were exposed to three different protocols to develop LVDD. First, rabbits were exposed to 0.5% cholesterol-rich diet for an average of 17 weeks. Second, rabbits were subjected to surgical ascending aortic constriction (AAC), to mimic the effect of fixed reduced aortic valve area, and studied after 10 weeks. The third model combined both cholesterol-enriched diet (for 12 weeks) and surgical AAC. The control group consisted of age-matched rabbits under normal diet. After development of LVDD, rabbits were randomized to receive infusions of saline or apoA-I mimetic (25 mg/kg) 3 times per week for 4 weeks. Detailed cardiac structure and function measurements were assessed at baseline and weekly during treatment period. Histological and molecular analyses were performed on LV samples.
Results
In the three models, echocardiographic results showed development of LVDD over time, with preserved LV systolic and aortic valve functions versus controls. ApoA-I mimetic infusions did not significantly improve echocardiographic parameters nor molecular markers of cardiac inflammation, oxidative stress and fibrosis.
Conclusion
ApoA-I mimetic therapy did not directly improve LVDD. These results indicate that previously observed changes of LVDD were caused by AVS improvement induced by this treatment.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 05 Jan 2021; epub ahead of print
Nachar W, Merlet N, Maafi F, Mihalache-Avram T, ... Rhéaume E, Tardif JC
Int J Cardiol: 05 Jan 2021; epub ahead of print | PMID: 33421451
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Impact:
Abstract

Constrictive pericarditis after open heart surgery: A-20 year case controlled study.

Moreyra AE, Cosgrove NM, Zinonos S, Yang Y, ... Kostis WJ,
Background
Constrictive pericarditis is a rare complication of open heart surgery (OHS), but little is known regarding the etiologic determinants, and prognostic factors. The purpose of this study was to investigate clinical predictors and long term prognosis of post-operative constrictive pericarditis (CP).
Methods
Using the Myocardial Infarction Data Acquisition System database, we analyzed records of 142,837 patients who were admitted for OHS in New Jersey hospitals between 1995 and 2015. Ninety-one patients were hospitalized with CP 30 days or longer after discharge from OHS. Differences in proportions were analyzed using Chi square tests. Controls were matched to cases for demographics, surgical procedure type, history of OHS, and propensity score. Cox proportional hazard models were used to evaluate the risk of all-cause death. Log-rank tests and Cox models were used to assess differences in the Kaplan-Meier survival curves with and without adjustments for comorbidities.
Results
Patients with CP were more likely to have history of valve disease (VD, p < 0.001), atrial fibrillation (AF, p = 0.024) renal disease (CKD, p = 0.028), hemodialysis (HD, p = 0.008), previous OHS (p < 0.001). Patients with CP compared to matched controls had a higher 7-year mortality (p < 0.001). This difference became statistically significant at 1-year after surgery.
Conclusion
CP is a rare complication of OHS that occurs more frequently in patients with VD, AF, CKD, HD, multiple OHS, and it is associated with an unfavorable long-term prognosis. Given the large number of OHS performed every year, the results highlight the need for clinicians to recognize and properly manage this complication of OHS.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 05 Jan 2021; epub ahead of print
Moreyra AE, Cosgrove NM, Zinonos S, Yang Y, ... Kostis WJ,
Int J Cardiol: 05 Jan 2021; epub ahead of print | PMID: 33421450
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Impact:
Abstract

Efficacy and safety of a magnesium stearate paclitaxel coated balloon catheter in the porcine coronary model.

Bettink S, Löchel M, Peters D, Haider W, Speck U, Scheller B
Background
Local administration of growth-inhibiting substances such as paclitaxel or sirolimus could reduce the risk of restenosis. In the drug coated balloon (DCB) technology the coating and the applied dose seem to play a major role. The aim of the present preclinical studies was to investigate the efficacy and safety of a specific DCB with paclitaxel as active ingredient and magnesium stearate as excipient.
Methods
Evaluation of the coating, drug release and transfer was done ex vivo and in vivo on peripheral arteries. A porcine coronary stent model was chosen to provoke intimal thickening. Conventional uncoated balloons were compared with paclitaxel urea and paclitaxel magnesium stearate coated balloons. QCA and histomorphometry was performed on treated vessels. Three areas of the heart were histologically examined for pathological changes.
Results
QCA and histomorphometry revealed no differences in baseline data between treatment groups. All DCB groups showed a significant reduction of angiographic and histologic parameters describing neointimal formation 4 weeks after treatment (e.g. mean angiographic late lumen loss all coated 0.31 ± 0.18 mm versus 0.91 ± 0.37 mm in the uncoated balloon group). There were no device-related animal deaths or clinical abnormalities. In spite of very slight-to-slight microscopic findings limited to small arterial vessels in downstream tissue there was no change in left ventricular ejection fraction or angiographic presentation of small side branches of treated arteries.
Conclusion
Paclitaxel DCB using stearate as excipient show a high efficacy in reducing neointima formation after experimental coronary intervention. No evidence of myocardial damage resulting from distal embolization was found.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 04 Jan 2021; epub ahead of print
Bettink S, Löchel M, Peters D, Haider W, Speck U, Scheller B
Int J Cardiol: 04 Jan 2021; epub ahead of print | PMID: 33418002
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Impact:
Abstract

Transcatheter aortic valve replacement in patients with extremely severe aortic stenosis.

Saji M, Higuchi R, Izumi Y, Takamisawa I, ... Takayama M, Isobe M
Background
Although most patients with severe aortic stenosis (AS) have high aortic valve velocities, outcomes of transcatheter aortic valve replacement (TAVR) in patients with extremely high aortic valve velocities remain unclear. We aimed to investigate the clinical outcomes of patients with peak aortic jet velocity (Vmax) values ≥ 6 m/s.
Methods
The study included 913 consecutive patients who underwent TAVR between 2013 and 2020. To better understand the impacts of the higher Vmax on outcomes, patients with Vmax values < 4.0 m/s, ejection fractions < 50%, valve-in-valve procedures, and unstable hemodynamics were excluded. Patients were grouped according to preprocedural Vmax as follows: 4-5 m/s, 5-6 m/s, and ≥ 6 m/s. According to guidelines describing Vmax ≥ 5.0 m/s as \"very\" severe AS, Vmax ≥ 6.0 m/s was defined as \"extremely\" severe AS in this study.
Results
New York Heart Association classification-III/IV and severe left ventricular hypertrophy were more frequent in the extremely severe AS group, which concurred with the advanced stage of severe AS, and they had a similar mortality rate to the other groups. Although they showed the greatest Vmax improvements after TAVR, they had higher paravalvular leak (PVL) rates. Even among the patients who received newer-generation transcatheter aortic valves, they had higher PVL rates, despite more frequent balloon dilation than the other groups.
Conclusion
Although patients with extremely severe AS have similar mortality rates to other patients with severe AS after TAVR, the risk of procedural complications caused by more frequent balloon dilation should be considered.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 04 Jan 2021; epub ahead of print
Saji M, Higuchi R, Izumi Y, Takamisawa I, ... Takayama M, Isobe M
Int J Cardiol: 04 Jan 2021; epub ahead of print | PMID: 33418001
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Impact:
Abstract

Long-term intermittent versus short continuous heart rhythm monitoring for the detection of atrial fibrillation recurrences after catheter ablation.

Hermans ANL, Gawalko M, Pluymaekers NAHA, Dinh T, ... Linz D, Luermans JGLM
Background
The utility of long-term intermittent heart rhythm monitoring after atrial fibrillation (AF) ablation remains unclear. Therefore, we compared the efficacy and usability of long-term intermittent (AliveCor Kardia® (ACK)) versus short continuous (Holter) heart rhythm monitoring for the detection of AF recurrences after AF ablation and evaluated ACK accuracy to detect AF.
Methods
Patients were provided with Holter (for ≥24 h) simultaneously with an ACK (4 weeks) used three times a day and in case of symptoms. The primary endpoint was the difference in proportion of patients diagnosed with recurrent AF by ACK as compared to Holter monitoring. Secondary endpoints were the usability (System Usability Scale and a four-item questionnaire) of ACK and Holter monitoring; and the accuracy of the ACK algorithm for AF detection.
Results
Out of 126 post-ablation patients, 115 (91.3%; 35 females, median age 64.0 [58.0-68.0] years) transmitted overall 7838 ACK ECG recordings. ACK and Holter monitoring detected 29 (25.2%) and 17 (14.8%) patients with AF recurrences, respectively (p < 0.001). More than 2 weeks of ACK monitoring did not have additional diagnostic yield for detection of AF recurrences. Patients graded ACK higher than Holter monitoring and found ACK more convenient in daily usage than Holter (p < 0.001). Sensitivity and specificity of ACK for AF detection were 95.3% and 97.5%, respectively.
Conclusions
Long-term intermittent monitoring by ACK more effectively detects AF recurrences after AF ablation and has a higher patients\' usability than short continuous Holter monitoring. ACK showed a high accuracy to detect AF.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 03 Jan 2021; epub ahead of print
Hermans ANL, Gawalko M, Pluymaekers NAHA, Dinh T, ... Linz D, Luermans JGLM
Int J Cardiol: 03 Jan 2021; epub ahead of print | PMID: 33412184
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Impact:
Abstract

Impact of a pharmacist-based multidimensional intervention aimed at decreasing the risk of hyperkalemia in heart failure patients: A Latin-American experience.

Gallo-Bernal S, Calixto CA, Molano-González N, Moreno MPD, ... Medina HM, Rodríguez MJ
Aims
Hyperkalemia is a potentially life-threatening condition associated with the use of heart failure (HF) medications, which can lead to increased morbidity and mortality. Novel approaches for hyperkalemia prevention are needed, especially in limited-resource settings. Despite multiple studies showing the beneficial impact of pharmaceutical-counseling in several outcomes, there is a knowledge-gap regarding its impact on hyperkalemia prevention.
Methods
A case-control study was performed in patients from the Adult Heart Failure Clinic Registry in our institution. Cases were selected using a definition of serum potassium K+ ≥5.5 mmol/L. To study the association between hyperkalemia and relevant risk factors, we performed a multivariate logistic regression analysis using the Least Absolute Shrinkage and Selection Operator (LASSO) method for variable selection. We also fitted a Classification and Regression Tree (CART) to establish complex interactions and effect modifiers between the selected variables.
Results
We matched 483 controls (eligible HF patients without hyperkalemia) to 132 cases (eligible HF patients with hyperkalemia based on age and calendar, yielding a total sample size of 615 patients (270 females) for this study. Cases had statistically significant lower odds of receiving a pharmacist-based multidimensional intervention (PBMI) (OR 0.57; 95% CI, 0.43-0.80) or having HF with reduced ejection fraction (OR 0.56; 95% CI, 0.18-0.72). On the other hand, patients who presented hyperkalemia had statistically significant higher odds of having a history of chronic kidney disease stage 4 (OR 4.97; 95% CI, 2.24-11.01) or 5 (OR 6.73; 95% CI, 1.69-26.84) and being on enalapril at doses =40 mg/day (OR, 9.90; 95% CI 5.81-16.87).
Conclusions
PBMI is a practical approach to prevent hyperkalemia in HF patients in a limited-resource setting. However, clinical trials are needed to assess its effectiveness.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 03 Jan 2021; epub ahead of print
Gallo-Bernal S, Calixto CA, Molano-González N, Moreno MPD, ... Medina HM, Rodríguez MJ
Int J Cardiol: 03 Jan 2021; epub ahead of print | PMID: 33412183
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Impact:
Abstract

Modern NCDR and ACTION risk models outperform the GRACE model for prediction of in-hospital mortality in acute coronary syndrome in a German cohort.

Parco C, Brockmeyer M, Kosejian L, Quade J, ... Kelm M, Wolff G
Background:
and purpose
Risk prediction with the Global Registry of Acute Coronary Events (GRACE) risk model is guideline-recommended in acute coronary syndrome (ACS) patients. However, the performance of more contemporary scores derived from ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and National Cardiovascular Data (NCDR) registries remains incompletely understood. We aimed to compare these models in German ACS patients.
Methods and results
A total of 1567 patients with (Non-)ST-segment elevation myocardial infarction (NSTEMI: 1002 patients, STEMI: 565 patients) undergoing invasive management at University Hospital Düsseldorf (Germany) from 2014 to 2018 were included. Overall in-hospital mortality was 7.5% (NSTEMI 3.7%, STEMI 14.5%). Parameters for calculation of GRACE 1.0, GRACE 2.0, ACTION and NCDR risk models and in-hospital mortality were assessed and risk model performance was compared. The GRACE 1.0 risk model for prediction of in-hospital mortality discriminated risk superior (c-index 0.84) to its successor GRACE 2.0 (c-index 0.79, P = 0.0008). The NCDR model performed best in discrimination of risk in ACS overall (c-index 0.89; P <0.0001; P <0.0001) and in NSTEMI and STEMI subgroups (P and P both <0.02). ACTION and GRACE risk models performed comparable to each other (both c-index 0.84, P=0.68), with advantages for ACTION in NSTEMI patients (c-index 0.87 vs. 0.84 (GRACE); P=0.02). ACTION and GRACE 2.0 showed the most accurate calibration of all models.
Conclusions
In a contemporary German patient population with ACS, modern NCDR and ACTION risk models showed superior performance in prediction of in-hospital mortality compared to the gold-standard GRACE model.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 03 Jan 2021; epub ahead of print
Parco C, Brockmeyer M, Kosejian L, Quade J, ... Kelm M, Wolff G
Int J Cardiol: 03 Jan 2021; epub ahead of print | PMID: 33412182
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Abstract

Transcatheter ablation of the Atrio-ventricular junction in refractory atrial fibrillation: A clinic-pathological study.

Rizzo S, Corrado A, De Gaspari M, Zoppo F, ... Basso C, Thiene G
Background
Catheter ablation of the specialized atrioventricular junction (AVJ) with a right-side approach is an effective therapy for refractory atrial fibrillation with fast ventricular rate. Our aim is to assess the efficacy of the procedure in a single center experience and investigate the histologic findings of AVJ after catheter ablation.
Methods
A) Analysis of AVJ ablation efficacy in a consecutive series of patients with refractory atrial fibrillation; B) Histo-pathologic study of the conduction system by serial section technique and clinical-electrophysiologic correlation in four patients who underwent AVJ ablation.
Results
A) Right sided AVJ ablation was successful in all 87 consecutive patients (mean procedural time 19.2±17.9 min). Energy applications ranged from 1 to 27 (mean 5.8±5.1) with eight patients (9%) requiring > 15 applications. B) Fibrotic disruption of AV node and/or His bundle interruption was found in three cases with previous AVJ ablation. In the case requiring a left side approach, the compact AV node and common His bundle appeared undamaged whereas extensive fibrosis of the summit of the ventricular septum, branching His bundle and proximal bundle branches was found.
Conclusion
Our data confirm that the ideal site for ablation of the specialized AVJ is the AV node. In selected cases with unsuccessful AV node ablation, a shift towards the His bundle is needed. A continuity between the septal and anterior leaflets of the tricuspid valve may protect the His bundle as to require multiple shocks and prolong the procedure.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 03 Jan 2021; epub ahead of print
Rizzo S, Corrado A, De Gaspari M, Zoppo F, ... Basso C, Thiene G
Int J Cardiol: 03 Jan 2021; epub ahead of print | PMID: 33412181
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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