Journal: Int J Cardiol

Sorted by: date / impact
Abstract

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

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

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

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

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 © 2021 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 May 2021; 331:46-56
Bettink S, Löchel M, Peters D, Haider W, Speck U, Scheller B
Int J Cardiol: 14 May 2021; 331:46-56 | PMID: 33418002
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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 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 May 2021; 331:199-205
Nachar W, Merlet N, Maafi F, Mihalache-Avram T, ... Rhéaume E, Tardif JC
Int J Cardiol: 14 May 2021; 331:199-205 | PMID: 33421451
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Abstract

Impact of history of depression on 1-year outcomes in patients with chronic coronary syndromes: An analysis of a contemporary, prospective, nationwide registry.

De Luca L, 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 B.V. All rights reserved.

Int J Cardiol: 14 May 2021; 331:273-280
De Luca L, Temporelli PL, Amico AF, Gonzini L, ... Gabrielli D, Gulizia MM
Int J Cardiol: 14 May 2021; 331:273-280 | PMID: 33422564
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Abstract

No antiarrhythmic effect of direct oral anticoagulants versus vitamin K antagonists in paroxysmal atrial fibrillation patients undergoing catheter ablation.

Zweiker D, Manninger M, Sieghartsleitner R, Ebner J, ... Schotten U, Scherr D
Introduction
Direct oral anticoagulants (DOACs) are superior to vitamin K antagonists (VKAs) for the prevention of stroke in atrial fibrillation (AF) patients with elevated stroke risk. Possible antiarrhythmic effects of DOACs have been discussed. We analyzed impact of DOAC treatment on recurrence-free survival after AF catheter ablation.
Methods
Two-hundred and thirty-nine consecutive patients (median age 57 [IQR 48-64] years, 26.4% female) undergoing ablation for paroxysmal AF were included into this study. 68.6% of them received DOACs (DOAC group), 31.4% VKA (VKA group). The primary outcome was arrhythmia-free one-year survival.
Results
DOAC patients had lower BMI, shorter history of AF, less arterial hypertension, less vascular disease, less use of antiarrhythmics and consequently lower CHA2DS2-VASc and HAS-BLED Scores. There was no difference in arrhythmia-free survival between DOAC and VKA groups (DOAC: 86.6%, VKA: 76.7%, p = 0.286).
Conclusions
Despite baseline characteristics favouring a better outcome of DOAC patients, arrhythmia-free survival was similar in both groups. Consequently, DOAC treatment did not have clinically relevant antiarrhythmic properties in these patients.

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

Int J Cardiol: 14 May 2021; 331:106-108
Zweiker D, Manninger M, Sieghartsleitner R, Ebner J, ... Schotten U, Scherr D
Int J Cardiol: 14 May 2021; 331:106-108 | PMID: 33508338
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Abstract

Current challenges for hypertension management: From better hypertension diagnosis to improved patients\' adherence and blood pressure control.

Parati G, Lombardi C, Pengo M, Bilo G, Ochoa JE
Hypertension control still remains a largely unmet challenge for public health systems. Despite the progress in blood pressure (BP) measurement techniques, and the availability of effective and safe antihypertensive drugs, a large number of hypertensive patients are not properly identified, and a significant proportion of those who receive antihypertensive treatment fail to achieve satisfactory control of their BP levels. It is thus not surprising that hypertension is still a major contributor to disease burden and disability worlwide, even in developed countries. This paper will address current challenges in hypertension management and potential strategies for an improvement in this field. In its first part relevant issues related to hypertension diagnosis will be addressed, in particular how to improve identification of sustained BP elevation and specific BP phenotypes such as white coat and masked hypertension trough the combined use of office and out-of-office BP monitoring techniques. In its second part focus will be on how to improve achievement of hypertension control in treated patients by optimization and simplification of medication regimens, including more efficient selection and titration of antihypertensive drugs and their combinations, aimed at achieving a more consistent 24hBP control; and by favoring a more active patients\' and physicians\' involvement in hypertension management also through BP telemonitoring and mobile health technologies.

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

Int J Cardiol: 14 May 2021; 331:262-269
Parati G, Lombardi C, Pengo M, Bilo G, Ochoa JE
Int J Cardiol: 14 May 2021; 331:262-269 | PMID: 33548384
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Abstract

Empagliflozin increases plasma levels of campesterol, a marker of cholesterol absorption, in patients with type 2 diabetes: Association with a slight increase in high-density lipoprotein cholesterol.

Jojima T, Sakurai S, Wakamatsu S, Iijima T, ... Usui I, Aso Y
Background:
and aims
Sodium/glucose cotransporter 2 (SGLT2) inhibitors decrease plasma triglyceride levels and slightly increase low-density lipoprotein (LDL-c) and high-density lipoprotein cholesterol (HDL-c). However, the mechanisms underlying such changes in the blood lipid profile remain to be determined. We investigated how empagliflozin affects plasma markers of cholesterol absorption and synthesis, and evaluated the relationship between changes in these markers and blood lipids in patients with type 2 diabetes.
Methods and results
In a randomized, active-controlled, open-label trial, 51 patients were randomly allocated in 2:1 ratio to receive empagliflozin 10 mg/day (n = 32) or standard therapy (n = 19) for 12 weeks. We measured plasma levels of lathosterol as a marker of cholesterol synthesis, and campesterol and sitosterol as markers of cholesterol absorption, at baseline and 12 weeks after treatment. In the empagliflozin group, serum HDL-c, but not LDL-c, significantly increased between baseline and 12 weeks (54.4 ± 16.3 vs. 58.8 ± 19.6 mg/dl; p = 0.0006), whereas in the standard therapy group, HDL-c and LDL-c remained unchanged. In the empagliflozin group, plasma campesterol also increased significantly (4.14 ± 1.88 vs. 4.90 ± 2.26 μg/ml, p = 0.0008), whereas no change in plasma campesterol or sitosterol was found in the control group. Although plasma lathosterol showed no change in the whole empagliflozin group, it decreased significantly in patients who were not taking statins. In statin non-users, plasma lathosterol decreased significantly after treatment with empagliflozin (2.71 ± 0.99 vs. 1.91 ± 0.99 μg/ml, p < 0.05). In the empagliflozin group, changes in plasma campesterol correlated positively with changes in HDL-c.
Conclusion
Empagliflozin increases serum campesterol, a marker of cholesterol absorption, in patients with type 2 diabetes. This increase may be associated with SGLT2 inhibitor-induced increases in HDL cholesterol.

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

Int J Cardiol: 14 May 2021; 331:243-248
Jojima T, Sakurai S, Wakamatsu S, Iijima T, ... Usui I, Aso Y
Int J Cardiol: 14 May 2021; 331:243-248 | PMID: 33556413
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Impact:
Abstract

Quantitative assessment of the entire right ventricle from one acoustic window: An attractive approach in patients with congenital heart disease in daily practice.

Van Berendoncks AML, Bowen DJ, McGhie J, Cuypers J, ... Roos-Hesselink J, Van den Bosch AE
Background
Right ventricular (RV) function is recognized as an important prognostic factor in adult congenital heart disease (ACHD). The accuracy of established parameters including tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC) and tissue Doppler imaging (TDI S\') is limited as only a small RV region is reflected. We previously introduced a novel four-view approach with different RV walls visualized from one apical view using electronic plane rotation, also known as iRotate.
Aim
To evaluate the entire RV function using electronic plane rotation echocardiography within the spectrum of ACHD compared with healthy subjects.
Methods and results
One hundred and forty-two ACHD patients were recruited from the outpatient clinic and 89 healthy subjects. All subjects underwent a transthoracic echocardiogram with evaluation of TAPSE, TDI S\' and peak systolic longitudinal RV strain (RV-LS) from all RV walls using the four-view electronic plane rotation model. With exception of TDI S\' in inferior coronal view, all parameters were lower in ACHD vs healthy subjects (p < 0.001). Within the ACHD patients, RV strain was lower in anterior (-15.9 ± 4.9) and inferior coronal view (-15.1 ± 4.5) versus lateral (-17.6 ± 5.0) and inferior wall (-17.2 ± 4.7) (p < 0.05). RV-LS values of systemic RV were lower (p < 0.05), but no difference was observed between subpulmonic RV loading conditions.
Conclusion
The four-view electronic plane rotation model represents a reproducible, easily applicable and complete RV assessment in daily practice. RV function is significantly decreased in the ACHD group using both regional and global assessment parameters. Complete RV strain analysis reveals regional differences.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 May 2021; 331:75-81
Van Berendoncks AML, Bowen DJ, McGhie J, Cuypers J, ... Roos-Hesselink J, Van den Bosch AE
Int J Cardiol: 14 May 2021; 331:75-81 | PMID: 33529669
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Impact:
Abstract

Effects of long-term right ventricular apex pacing on left ventricular dyssynchrony, morphology and systolic function.

Xin MK, Gao P, Zhang SY
Background
Right ventricular apex (RVA) is still the most common implanted site in the world. There are a large number of RVA pacing population who have been carrying dual-chamber permanent pacemaker (PPM) over decades. Comparison of left ventricular dyssynchrony, morphology and systolic function between RVA pacing population and healthy population is unknown.
Method
This case-control study enrolled 61 patients suffered from complete atrioventricular block (III°AVB) for replacement of dual-chamber PPM. Then, 61 healthy controls matched with PPM patients in gender, age, follow-up duration and complications were included. The lead impedance, pacing threshold and sensing were compared between at implantation and long-term follow-up. Left ventricular (LV) dyssynchrony, morphology and systolic function were compared between RVA pacing population (RVA group) and healthy population (healthy group) at implantation (baseline) and follow-up. And clarify the predictors of LV systolic function in RVA group at follow-up.
Results
After 112.44 ± 34.94 months of follow-up, comparing with parameters at implantation, atrial lead impedance decreased significantly (690 ± 2397 Ω vs 613 ± 2257 Ω, p = 0.048); atrial pacing threshold has a increased trend and P-wave amplitude has a decreased trend, but there was no statistical differences; while, RVA ventricular lead threshold increased significantly (0.50 ± 0.23 V vs 0.91 ± 0.47 V, p < 0.001), impedance (902 ± 397 Ω vs 680 ± 257 Ω,p < 0.001) and R-wave amplitude (11.71 ± 9.40mv vs 7.00 ± 6.91 mv, p < 0.001) decreased significantly. Compared with healthy group, long-term RVA pacing significantly increased ventricular dyssynchrony (mean QRS duration, 156.21 ± 29.80 ms vs 97.08 ± 15.70 ms, p < 0.001), left atrium diameter (LAD, 40.61 ± 6.15 mm vs 37.49 ± 4.80 mm,p = 0.002), left ventricular end-diastolic diameter (LVEDD, 49.15 ± 5.93 mm vs 46.41 ± 3.80 mm,p = 0.003), left ventricular hypertrophy (LVMI, 121.86 ± 41.52 g/m2 vs 98.41 ± 25.29 g/m2,p < 0.001), significantly deteriorated degree of tricuspid regurgitation (p < 0.001), and significantly decreased left ventricular ejection fraction (LVEF, 61.38 ± 8.10% vs 64.64 ± 5.85%, p = 0.012), but after long-term RVA pacing, the mean LVEF was still more than 50%. Long-term RVA group LVEF was negatively correlated with preimplantation LVMI (B = -0.055,t = -2.244,p = 0.029), LVMI at follow-up (B = -0.081,t = -3.864,p = 0.000) and tricuspid regurgitation at follow-up (B = -3.797,t = -3.599,p = 0.001).
Conclusion
In conclusion, although long-term RVA pacing has significantly effects on left ventricular dyssynchrony, morphology and systolic function in III°AVB patients, the mean LVEF is still >50%. High preimplantation LVMI can predict the decline of LVEF.

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

Int J Cardiol: 14 May 2021; 331:91-99
Xin MK, Gao P, Zhang SY
Int J Cardiol: 14 May 2021; 331:91-99 | PMID: 33529668
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Abstract

A new approach to the clinical subclassification of heart failure with preserved ejection fraction.

Nouraei H, Rabkin SW
Objective
Heart failure with preserved ejection (HFpEF) represents nearly half of all patients with heart failure (HF). The objective of this study was to determine whether patient characteristics identify discrete kinds of HFpEF.
Methods
Data were collected on 196 patients with HFpEF in a non-hospitalized setting. Clinical and laboratory variables were collected, and 47 candidate variables were examined by the unsupervised clustering strategy partitioning around medoids. The Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) risk score was calculated. Follow-up data on all-cause mortality, cardiovascular mortality, and HF exacerbation, were collected and were not part of the data used to identify subgroups.
Results
Six significantly different groups or clusters were found. There were three groups of women (i) individuals with a low proportion of vascular risk factors (HFpEF1) (ii) individuals with a high proportion of hypertension and diabetes, but lower proportion of kidney disease and diastolic dysfunction (HFpEF3) (iii) older individuals with high rates of atrial fibrillation (AF), chronic kidney disease. They had the worst long-term outcomes (HFpEF4). There were three groups of men (i) individuals with a high proportion of coronary artery disease (CAD), dyslipidemia, higher serum creatinine, and diastolic dysfunction (HFpEF2)(ii) individuals with highest BMI, and high proportion of CAD, obstructive sleep apnea, and poorly controlled diabetes (HFpEF5) (iii) individuals with high rates of AF, elevated BNP, biventricular remodeling (HFpEF6). They had a high cardiovascular mortality.
Conclusions
HFpEF consists of a heterogenous group of individuals with six distinct clinical subsets that have different long-term outcomes.

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

Int J Cardiol: 14 May 2021; 331:138-143
Nouraei H, Rabkin SW
Int J Cardiol: 14 May 2021; 331:138-143 | PMID: 33529665
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Impact:
Abstract

Influence of age on the relationship between apixaban concentration and anti-factor Xa activity in older patients with non-valvular atrial fibrillation.

Kalaria SN, Zhu H, Liu Q, Florian J, Wang Y, Schwartz J
Background/objectives
Despite lower major bleeding rates associated with direct oral anticoagulants (DOACs) as compared to conventional warfarin therapy, bleeding rates remain higher in older patients compared to younger patients suggesting a potential role for DOAC measurements. The objective of this study is to examine the effect of age on the relationship between apixaban concentrations and anti-Factor Xa activity in patients with non-valvular atrial fibrillation (NVAF).
Methods
This is a retrospective analysis based on a database created using data from the ARISTOTLE study. Outpatient, stable adult patients with NVAF receiving apixaban were included in this study. Data collection consisted of apixaban concentration, anti-Factor Xa activity, age, weight, creatinine, and co-medications.
Results
The database composed of 2058 patients receiving apixaban. Distribution of race, NVAF subtype, and aspirin use was fairly similar across each age quantile. Older patients received a higher number of co-medications and received the 2.5 mg apixaban dose more often as compared to younger patients (22% vs. < 1%). Linear regression demonstrated that the unadjusted slope for apixaban concentration effect on anti-Factor Xa activity was similar across each age quantile. Although, the overall adjusted linear regression analysis demonstrated that the age by concentration interaction was statistically significant, relative differences in anti-Factor Xa activity (< 8%) were not clinically meaningful.
Conclusion
Data on apixaban concentrations and anti-Factor Xa activity from a pivotal randomized double-blind study of apixaban for the prevention of stroke in NVAF patients have confirmed that the chromogenic anti-Factor Xa activity assay can accurately assess apixaban concentrations in patients regardless of age. Age was not associated with a clinically relevant change in the apixaban vs. anti-Factor Xa activity response relationship and target ranges are unchanged.

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

Int J Cardiol: 14 May 2021; 331:109-113
Kalaria SN, Zhu H, Liu Q, Florian J, Wang Y, Schwartz J
Int J Cardiol: 14 May 2021; 331:109-113 | PMID: 33529664
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Impact:
Abstract

Single versus double use of a suture-based closure device for transfemoral aortic valve implantation.

Reifart J, Liebetrau C, Weferling M, Dörr O, ... Hamm CW, Kim WK
Background
The most common method of percutaneous closure in transfemoral transcatheter aortic valve implantation (TAVI) employs two obtusely oriented ProGlide devices. The aim of this study was to assess the feasibility and safety of using a single ProGlide system for primary access site closure in comparison with the double ProGlide approach in an all-comers TAVI population.
Methods
Between March 2016 and December 2018, a total of 1105 patients underwent transfemoral TAVI for severe aortic stenosis at our center. Application of two ProGlide systems was standard until April 2017 (n = 432), whereas thereafter a single ProGlide system was used (n = 663). A 1:1 propensity score matching was performed to adjust for baseline differences between the two groups, resulting in 327 matched cases. Primary outcomes of interest were main access site-related vascular complications.
Results
The mean number of ProGlide devices used per patient was 1.03 (SD 0.2) in the single-ProGlide group versus 2.01 (SD 0.14) in the double-ProGlide group. An additional vascular closure device was required to obtain full hemostasis in 23.2% versus 9.5% of patients (p < 0.001) in the two groups, respectively. Technical success of ProGlide usage was similar (94.3% versus 92.1%, p = 0.163). In the matched cohorts, the rates of main access site-related major vascular complications were similar (4.0% vs. 6.4%, p = 0.217).
Conclusion
The single-ProGlide technique is feasible, with rates of technical success similar to those of the double-ProGlide technique. Use of this method did not lead to more frequent access site-related complications but was more cost effective than the double-ProGlide approach.

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

Int J Cardiol: 14 May 2021; 331:183-188
Reifart J, Liebetrau C, Weferling M, Dörr O, ... Hamm CW, Kim WK
Int J Cardiol: 14 May 2021; 331:183-188 | PMID: 33529662
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Abstract

The role of Saccharibacteria (TM7) in the subginival microbiome as a predictor for secondary cardiovascular events.

Schulz S, Reichert S, Grollmitz J, Friebe L, ... Klawonn F, Shi R
Background
The composition of the subgingival microbiota is of great importance in both oral and systemic diseases. However, a possible association of the oral microbiome and cardiovascular (CV) outcome has not yet been considered in a complex model. The primary objective of the study (DRKS-ID: DRKS00015776) was to assess differences in complex subgingival bacterial composition, depending on the CV outcome in patients undergoing Coronary Artery Bypass Grafting Surgery (CABG).
Material and methods
We conducted a longitudinal cohort study enrolling 102 CV patients. After a one-year follow-up, the postoperative outcome was evaluated applying MACCE (Major Adverse Cardiac and Cerebrovascular Events) criteria. The complex oral microbiome was evaluated depending on CV outcome. The mathematical data processing included Qiime 2 software workflow and DADA2 pipeline as well as Human Oral Microbiome Database (HOMD) and Greengenes database classification. For identifying biomarkers distinguishing patients suffering from secondary CV events, the Cox Proportional Hazard Model for survival analysis was applied.
Results
In total, 19,418 Operational Taxonomic Units (OTU) were mapped according to the HOMD and Greengenes database. No significant differences in alpha and beta diversity were linked to CV outcomes (Shannon index; Principal Coordinates Analysis). No biomarker predicting secondary CV events were identified applying the area under the receiver operating characteristic curve (AUC) model. However, in survival analysis, one biomarker of Saccharibacteria phylum (class: TM7-3, order: CW040, family: F16) was associated with the incidence of a secondary CV event (p = 0.016).
Conclusions
For the first time, a subgingival biomarker has been identified that supports a cardiovascular prognosis in CV patients undergoing coronary artery bypass grafting.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 May 2021; 331:255-261
Schulz S, Reichert S, Grollmitz J, Friebe L, ... Klawonn F, Shi R
Int J Cardiol: 14 May 2021; 331:255-261 | PMID: 33529661
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Impact:
Abstract

Using existing technology better: Improving outcomes with the HeartWare left ventricular assist device.

MacGowan GA, Woods A, Robinson-Smith N, Tovey S, ... O\'Leary D, Schueler S
Background
The HeartWare left ventricular assist device has been in use for over 12 years. We sought to determine how outcomes at our centre have improved over time.
Methods
Review of electronic hospital records at the Freeman Hospital, Newcastle upon Tyne, United Kingdom.
Results
A total of 255 first time adult implants were divided into 2 eras: Era 1: 2009-2015 (N = 154) and Era 2: 2016-2020 (N = 101). We prospectively aimed to avoid higher risk Intermacs Classifications in Era 2, which resulted in significant changes in Intermacs class to lower risk in Era 2 (P < 0.001). There was a significant improvement in survival in Era 2, with 1 year survival increasing from 70 to 80% (P < 0.05). This was particularly associated with lower 30 day mortality in Era 2 (1.7 ± 2.3 vs 15.5 ± 7%, P < 0.005). This was associated with better right ventricular function in Era 2, and there was a trend to more temporary right ventricular assist devices used in Era 2 (28 ± 13 vs 12 ± 14%, P = 0.06). Deaths from intracranial haemorrhage, sepsis and right heart failure were unchanged between eras, though there was a trend towards less deaths in Era 2 from combined thromboses deaths (stroke and device thrombosis; 3.3 ± 5.4 vs 11.1 ± 7.4%, P = 0.07).
Conclusions
Better patient selection in association with more use of temporary right ventricular assist support has resulted in a significant improvement in survival. Intracranial haemorrhage, sepsis and right heart failure remain significant problems.

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

Int J Cardiol: 14 May 2021; 331:35-39
MacGowan GA, Woods A, Robinson-Smith N, Tovey S, ... O'Leary D, Schueler S
Int J Cardiol: 14 May 2021; 331:35-39 | PMID: 33529660
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Impact:
Abstract

Application of cardiac computed tomographic imaging and fluoroscopy fusion for guiding left atrial appendage occlusion.

Chen T, Liu G, Mu Y, Xu WH, ... Guo J, Chen YD
Objective
Evaluate the value of 3D computed tomography (CT) and CT-integrating fluoroscopy for procedural guidance during WATCHMAN implantation.
Methods
This observational study compared the clinical and procedural parameters for LAAO with and without fusion imaging. Forty-one pairs of patients-matched by procedure month and with or without the use of the image fusion system-were enrolled. Using the image fusion Advanced Workstation 4.6 software (GE Healthcare), we identified the 3D cardiac anatomy and safe zones for septal punch. The LAA orifice anatomy outlines were then projected onto the real-time fluoroscopy image during the procedure to guide all the steps of LAAO.
Results
The use of image fusion significantly reduced the procedural time, compared to the time required for the control group (44.73 ± 20.03 min vs. 63.73 ± 26.10 min, respectively; P < 0.001). When compared to the standard procedure, the use of image fusion significantly reduced both the total radiation dose (448.80 ± 556.35 mGy vs. 798.42 ± 616.34 mGy; P = 0.004) and dose area product (DAP) (38.03 ± 47.15 Gy∙cm2 vs. 67.66 ± 52.23 Gy∙cm2, P = 0.004). Corresponding to the radiation dose, the contrast volume was also reduced (67.32 ± 18.65 vs. 90.98 ± 25.03 ml; P = 0.0004). During short-term follow-up at 6 months, there was only one femoral hematoma and incomplete LAA sealing (>3 mm) in either group.
Conclusions
Automated real-time integration of cardiac CT and fluoroscopy is feasible, safe, and applicable in LAAO. It may significantly reduce the radiation exposure, procedure duration, and volume of contrast media. Following these results, the potential of merging reconstructed 3D CT scans with real-time coronary angiography should be fully exploited in LAAO.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 May 2021; 331:289-295
Chen T, Liu G, Mu Y, Xu WH, ... Guo J, Chen YD
Int J Cardiol: 14 May 2021; 331:289-295 | PMID: 33529659
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Impact:
Abstract

Coronary plaque assessment of Vasodilative capacity by CT angiography effectively estimates fractional flow reserve.

Varga-Szemes A, Schoepf UJ, Maurovich-Horvat P, Wang R, ... Emrich T, Buckler AJ
Background
To evaluate the feasibility of non-invasive fractional flow reserve (FFR) estimation using histologically-validated assessment of plaque morphology on coronary CTA (CCTA) as inputs to a predictive model further validated against invasive FFR.
Methods
Patients (n = 113, 59 ± 8.9 years, 77% male) with suspected coronary artery disease (CAD) who had undergone CCTA and invasive FFR between August 2013 and May 2018 were included. Commercially available software was used to extract quantitative plaque morphology inclusive of both vessel structure and composition. The extracted plaque morphology was then fed as inputs to an optimized artificial neural network to predict lesion-specific ischemia/hemodynamically significant CAD with performance validated by invasive FFR.
Results
A total of 122 lesions were considered, 59 (48%) had low FFR values. Plaque morphology-based FFR assessment achieved an area under the curve, sensitivity and specificity of 0.94, 0.90 and 0.81, respectively, versus 0.71, 0.71, and 0.50, respectively, for an optimized threshold applied to degree of stenosis. The optimized ridge regression model for continuous value estimation of FFR achieved a cross-correlation coefficient of 0.56 and regression slope of 0.59 using cross validation, versus 0.18 and 0.10 for an optimized threshold applied to degree of stenosis.
Conclusions
Our results show that non-invasive plaque morphology-based FFR assessment may be used to predict lesion-specific ischemia resulting in hemodynamically significant CAD. This substantially outperforms degree of stenosis interpretation and has a comparable level of sensitivity and specificity relative to publicly reported results from computational fluid dynamics-based approaches.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 May 2021; 331:307-315
Varga-Szemes A, Schoepf UJ, Maurovich-Horvat P, Wang R, ... Emrich T, Buckler AJ
Int J Cardiol: 14 May 2021; 331:307-315 | PMID: 33529657
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Impact:
Abstract

Prognostic nutritional index and the risk of mortality in patients with hypertrophic cardiomyopathy.

Wang Z, Zhao L, He S
Aims
Nutritional status has been related to clinical outcomes in patients with cardiovascular diseases. The prognostic impact of poor nutritional status in hypertrophic cardiomyopathy (HCM) is not clearly understood. The aim of the present study is to investigate the prognostic value of prognostic nutritional index (PNI), calculated from serum albumin level and total lymphocyte count, in HCM patients.
Methods
A total of 393 HCM patients in a tertiary medical centre were enrolled. The primary and secondary endpoints were all-cause mortality and cardiovascular death. The association between PNI and endpoints was analysed.
Results
During a mean follow-up duration of 4.8 years, patients with high PNI values (PNI ≥ 48.8) had significantly lower incidence of all-cause mortality (9.3% vs. 33.1%, P < 0.001) and cardiovascular death (7.1% vs. 21.0%, P < 0.001). After adjusting for potential confounders, PNI was independently associated with all-cause mortality and cardiovascular death (hazard ratio per 1 SD increase: 0.46 [95% CI: 0.34-0.62, P < 0.001] and 0.44 [95% CI: 0.30-0.63, P < 0.001]). In subgroup analysis stratified by age, gender, New York Heart Association class, atrial fibrillation, estimated glomerular filtration rate, left ventricular ejection fraction or left ventricular outflow tract obstruction, PNI was consistently related to mortality.
Conclusions
PNI is an independent prognostic factor for mortality in patients with HCM.

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

Int J Cardiol: 14 May 2021; 331:152-157
Wang Z, Zhao L, He S
Int J Cardiol: 14 May 2021; 331:152-157 | PMID: 33529655
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Impact:
Abstract

A critical analysis of 57 cases of Hughes-Stovin syndrome (HSS). A report by the HSS International Study Group (HSSISG).

Emad Y, Ragab Y, Kechida M, Guffroy A, ... Saad A, Rasker JJ
Background
Hughes-Stovin syndrome (HSS) is a systemic disease characterized by widespread vascular thrombosis and pulmonary vasculitis with serious morbidity and mortality. The HSS International Study Group is a multidisciplinary taskforce aiming to study HSS, in order to generate consensus recommendations regarding diagnosis and treatment.
Methods
We included 57 published cases of HSS (43 males) and collected data regarding: clinical presentation, associated complications, hemoptysis severity, laboratory and computed tomography pulmonary angiography (CTPA) findings, treatment modalities and cause of death.
Results
At initial presentation, DVT was observed in 29(33.3 %), thrombophlebitis in 3(5.3%), hemoptysis in 24(42.1%), and diplopia and seizures in 1 patient each. During the course of disease, DVT occurred in 48(84.2%) patients, and superficial thrombophlebitis was observed in 29(50.9%). Hemoptysis occurred in 53(93.0%) patients and was fatal in 12(21.1%). Pulmonary artery (PA) aneurysms (PAAs) were bilateral in 53(93%) patients. PAA were located within the main PA in 11(19.3%), lobar in 50(87.7%), interlobar in 13(22.8%) and segmental in 42(73.7%). Fatal outcomes were more common in patients with inferior vena cava thrombosis (p = 0.039) and ruptured PAAs (p < 0.001). Death was less common in patients treated with corticosteroids (p < 0.001), cyclophosphamide (p < 0.008), azathioprine (p < 0.008), combined immune modulators (p < 0.001). No patients had uveitis; 6(10.5%) had genital ulcers and 11(19.3%) had oral ulcers.
Conclusions
HSS may lead to serious morbidity and mortality if left untreated. PAAs, adherent in-situ thrombosis and aneurysmal wall enhancement are characteristic CTPA signs of HSS pulmonary vasculitis. Combined immune modulators contribute to favorable outcomes.

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

Int J Cardiol: 14 May 2021; 331:221-229
Emad Y, Ragab Y, Kechida M, Guffroy A, ... Saad A, Rasker JJ
Int J Cardiol: 14 May 2021; 331:221-229 | PMID: 33529654
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Impact:
Abstract

Prognostic utility of the assessment of diastolic function in patients undergoing cardiac resynchronization therapy.

Galli E, Smiseth OA, Aalen JM, Larsen CK, ... Voigt JU, Donal E
Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function.
Aims:
of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND
Results:
One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06).
Conclusions:
The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response.


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

Int J Cardiol: 14 May 2021; 331:144-151
Galli E, Smiseth OA, Aalen JM, Larsen CK, ... Voigt JU, Donal E
Int J Cardiol: 14 May 2021; 331:144-151 | PMID: 33535079
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Impact:
Abstract

Short- and long-term cost-effectiveness analysis of CYP2C19 genotype-guided therapy, universal clopidogrel, versus universal ticagrelor in post-percutaneous coronary intervention patients in Qatar.

AlMukdad S, Elewa H, Arafa S, Al-Badriyeh D
Background
Patients having CYP2C19 loss-of-function alleles and receiving clopidogrel are at higher risk of adverse cardiovascular outcomes. Ticagrelor is an effective antiplatelet that is unaffected by the CYP2C19 polymorphism. The main aim of the current research is to evaluate the cost-effectiveness among CYP2C19 genotype-guided therapy, universal ticagrelor, and universal clopidogrel after a percutaneous coronary intervention (PCI).
Methods
A two-part decision-analytic model, including a one-year model and a 20-year follow-up Markov model, was created to follow the use of (i) universal clopidogrel, (ii) universal ticagrelor, and (iii) genotype-guided antiplatelet therapy. Outcome measures were the incremental cost-effectiveness ratio (ICER, cost/success) and incremental cost-utility ratio (ICUR, cost/quality-adjusted life years [QALY]). Therapy success was defined as survival without myocardial infarction, stroke, cardiovascular death, stent thrombosis, and no therapy discontinuation because of adverse events, i.e. major bleeding and dyspnea. The model was based on a multivariate analysis, and a sensitivity analysis confirmed the robustness of the model outcomes, including against variations in drug acquisition costs.
Results
Against universal clopidogrel, genotype-guided therapy was cost-effective over the one-year duration (ICER, USD 6102 /success), and dominant over the long-term. Genotype-guided therapy was dominant against universal ticagrelor over the one-year duration, and cost-effective over the long term (ICUR, USD 1383 /QALY). Universal clopidogrel was dominant over ticagrelor for the short term, and cost-effective over the long-term (ICUR, USD 10,616 /QALY).
Conclusion
CYP2C19 genotype-guided therapy appears to be the preferred antiplatelet strategy, followed by universal clopidogrel, and then universal ticagrelor for post-PCI patients in Qatar.

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

Int J Cardiol: 14 May 2021; 331:27-34
AlMukdad S, Elewa H, Arafa S, Al-Badriyeh D
Int J Cardiol: 14 May 2021; 331:27-34 | PMID: 33535078
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Impact:
Abstract

Characteristics, trends, outcomes, and costs of stimulant-related acute heart failure hospitalizations in the United States.

Shetty S, Malik AH, Ali A, Yang YC, Briasoulis A, Alvarez P
Background
Heart failure (HF) hospitalizations remains a significant burden on the health care system. Stimulants including cocaine, amphetamine and its derivatives are amongst the most used illegal substances in the United States. The information regarding stimulant-related HF hospitalizations is scarce. We sought to evaluate the characteristics and trends of stimulant-related HF hospitalizations in the United States and their associated outcomes and resource utilization.
Methods
Using the National Inpatient Sample (NIS), we identified patients with a primary diagnosis of HF hospitalization. These hospitalizations were further divided into those with and without a concomitant diagnosis of stimulant (cocaine or amphetamine) dependence or abuse. Survey specific techniques were employed to compare trends in baseline characteristics, complications, procedures, outcomes and resource utilization between the two cohorts.
Results
We identified 9,932,753 hospitalizations (weighted) with a primary diagnosis of heart failure, of those 138,438 (1.39%) had a diagnosis of active stimulant use. The proportion of stimulant-related HF hospitalization is on the rise (1.1% to 1.9%). Stimulant-related HF hospitalization was highest amongst age group 30-39 years and 7.9% of HF hospitalizations in this age group were due to stimulant use. The proportion of stimulant-related HF hospitalization for the White and Hispanic race has doubled from 2008 to 2017. Stimulant-related HF hospitalization is associated with increased incidence of in-hospital complications like cardiogenic shock, acute kidney injury and ventricular tachycardia. These patients have more than 7-fold higher discharge against medical advice.
Conclusions
Stimulant-related HF hospitalizations have been increasing. It is associate with significant morbidity burden and health care utilization.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 May 2021; 331:158-163
Shetty S, Malik AH, Ali A, Yang YC, Briasoulis A, Alvarez P
Int J Cardiol: 14 May 2021; 331:158-163 | PMID: 33535075
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Impact:
Abstract

Treatment of atherosclerosis through transplantation of endothelial progenitor cells overexpressing dimethylarginine dimethylaminohydrolase (DDAH) in rabbits.

Shoeibi S, Mahdipour E, Mohammadi S, Moohebati M, Ghayour-Mobarhan M
Background
Endothelial dysfunction is a key event in the development of vascular diseases, including atherosclerosis. Endothelial progenitor cells (EPCs) play an important role in vascular repair. Decreased dimethylarginine dimethylaminohydrolase (DDAH) activity is observed in several pathological conditions, and it is associated with an increased risk of vascular disease. We hypothesized that bone marrow-derived EPCs and combination therapy with DDAH2-EPCs could reduce plaque size and ameliorate endothelial dysfunction in an atherosclerosis rabbit model.
Method
Four groups of rabbits (n = 8 per group) were subjected to a hyperlipidemic diet for a month. After establishing the atherosclerosis model, rabbits received 4 × 106 EPC, EPCs expressing DDAH2, through femoral vein injection, or saline (the control group with basic food and the untreated group). One month after transplantation, plaque thickness, endothelial function, oxidative stress, and inflammatory mRNAs, DDAH, and eNOS function were assessed.
Results
DDAH2-EPCs transplantation (p < 0.05) and EPCs transplantation (p < 0.05) were both associated with a reduction in plaque size compared to the control saline injection. The antiproliferative and antiatherogenic effects of EPCs were further enhanced by the overexpression of DDAH2 (p < 0.05, DDAH2-EPCs vs. EPCs). Furthermore, DDAH2-EPCs transplantation significantly increased endothelium integrity compared to the EPCs transplantation.
Conclusion
Transplantation of EPCs overexpressing DDAH2 may enhance the repair of injured endothelium by reducing inflammation and restoring endothelial function. Therefore, pCMV6-mediated DDAH2 gene-transfected EPCs are a potentially valuable tool for the treatment of atherosclerosis.

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

Int J Cardiol: 14 May 2021; 331:189-198
Shoeibi S, Mahdipour E, Mohammadi S, Moohebati M, Ghayour-Mobarhan M
Int J Cardiol: 14 May 2021; 331:189-198 | PMID: 33535073
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Impact:
Abstract

Morphology display and hemodynamic testing using 3D printing may aid in the prediction of LVOT obstruction after mitral valve replacement.

Wang H, Song H, Yang Y, Wu Z, ... Zhou Q, Guo R
Aims
Left ventricular outflow tract(LVOT) obstruction after mitral valve replacement can be life-threatening once occur. We simulated mitral valve replacement preoperatively using dynamic, three-dimensional(3D) printed models to help predict LVOT obstruction in this study.
Methods
56 patients who underwent mitral valve replacement were included. Prediction of LVOT obstruction in vitro was based on the data from 4 sources: digital, anatomical, flexible, and dynamic model. Digital 3D models were designed based on computed tomography (CT) image dataset and printed with photopolymer resin to create a 3D anatomical model, which contributed to the morphology display. Then, flexible models were made from specialized silicone, which is similar to cardiac tissue in terms of its softness and elasticity. Dynamic function was achieved by coupling flexible models to a mock circulatory system (MCS). Besides, surgery simulation and hemodynamic testing was done using dynamic 3D printed model and patients were regrouped based on hemodynamic change. Finally, different methods for prediction of LVOT obstruction as well as classification based on two-dimensional image data and dynamic model were compared with surgical results as golden standard.
Results
(1)Qualitatively, the prediction of LVOT obstruction using the dynamic 3D model was the most accurate and was consistent with clinical outcomes. In the four patients who developed LVOT obstruction after surgery, only two were at a high risk based on the other three models. (2)Quantitatively, the area of neo-LVOT predicted by the digital, anatomical, and flexible models was higher compared with the dynamic models and in-vivo after surgery. (3)Classification based on traditional criteria(two-dimensional image data) was different from surgical results. While the difference between dynamic model and surgical results was not statistically different.
Conclusions
After coupling the flexible model with the mock circulatory system, the dynamic 3D model predicted LVOT obstruction more accurately with hemodynamic testing compared with morphological evaluation. 3D printing can assist surgeons to better plan mitral valve replacement than traditional image data.

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

Int J Cardiol: 14 May 2021; 331:296-306
Wang H, Song H, Yang Y, Wu Z, ... Zhou Q, Guo R
Int J Cardiol: 14 May 2021; 331:296-306 | PMID: 33535072
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Impact:
Abstract

Standard and emerging CMR methods for mitral regurgitation quantification.

Fidock B, Archer G, Barker N, Elhawaz A, ... Myerson S, Garg P
Background
There are several methods to quantify mitral regurgitation (MR) by cardiovascular magnetic resonance (CMR). The interoperability of these methods and their reproducibility remains undetermined.
Objective
To determine the agreement and reproducibility of different MR quantification methods by CMR across all aetiologies.
Methods
Thirty-five patients with MR were recruited (primary MR = 12, secondary MR = 10 and MVR = 13). Patients underwent CMR, including cines and four-dimensional flow (4D flow). Four methods were evaluated: MRStandard (left ventricular stroke volume - aortic forward flow by phase contrast), MRLVRV (left ventricular stroke volume - right ventricular stroke volume), MRJet (direct jet quantification by 4D flow) and MRMVAV (mitral forward flow by 4D flow - aortic forward flow by 4D flow). For all cases and MR types, 520 MR volumes were recorded by these 4 methods for intra-/inter-observer tests.
Results
In primary MR, MRMVAV and MRLVRV were comparable to MRStandard (P > 0.05). MRJet resulted in significantly higher MR volumes when compared to MRStandard (P < 0.05) In secondary MR and MVR cases, all methods were comparable. In intra-observer tests, MRMVAV demonstrated least bias with best limits of agreement (bias = -0.1 ml, -8 ml to 7.8 ml, P = 0.9) and best concordance correlation coefficient (CCC = 0.96, P < 0.01). In inter-observer tests, for primary MR and MVR, least bias and highest CCC were observed for MRMVAV. For secondary MR, bias was lowest for MRJet (-0.1 ml, PNS).
Conclusion
CMR methods of MR quantification demonstrate agreement in secondary MR and MVR. In primary MR, this was not observed. Across all types of MR, MRMVAV quantification demonstrated the highest reproducibility and consistency.

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

Int J Cardiol: 14 May 2021; 331:316-321
Fidock B, Archer G, Barker N, Elhawaz A, ... Myerson S, Garg P
Int J Cardiol: 14 May 2021; 331:316-321 | PMID: 33548381
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Impact:
Abstract

Acute electrical, autonomic and structural effects of binge drinking: Insights into the \'holiday heart syndrome\'.

Voskoboinik A, McDonald C, Chieng D, O\'Brien J, ... Taylor AJ, Kistler PM
Background
Binge drinking is a common atrial fibrillation (AF) trigger, however the mechanisms are poorly understood.
Objective
To investigate the effects of alcohol intoxication and hangover with rhythm monitoring and cardiac MRI.
Methods
Patients underwent serial cardiac MRI pre- and post-binge with continuous Holter monitoring. Time periods analyzed: baseline (24 h pre-binge), consumption, hangover (0- 24 h post-consumption) and post-hangover (24-48 h post-consumption).
Results
50 patients (age 49 ± 15 years, 40% paroxysmal AF) completed the study (intake 8.4 ± 3.1 standard drinks). Mean heart rate increased from 72 ± 10 to 80 ± 13 beats per minute (bpm) during consumption (p < 0.001). The hangover period was characterised by higher daily atrial ectopic count (50, IQR 10-132 vs baseline 43, IQR 10-113; p = 0.04) and reduced heart rate variability (SDNN 55 ms, IQR 40-65 versus 62 ms, IQR 51-66; p = 0.007). There was evidence of heightened parasympathetic activity post-hangover with heart rate slowing (mean HR 54 ± 6 bpm; p = 0.03) and increased activity in the High frequency band when separating the complex heart rate variability waveform into its component rhythms (291 ms2, 97-538 versus baseline 237 ms2, IQR 104-332; p = 0.04). Three patients developed AF 11, 29 and 34 h post-binge. Cardiac MRI (2.7 ± 0.7 days post-binge) demonstrated a decrease in left atrial (LA) emptying fraction (57.9 ± 8.5 to 53.5 ± 6.7%; p = 0.003) but no change in LA volume, left ventricular ejection fraction or markers of ventricular inflammation.
Conclusion
Binge drinking is associated with sympathetic activation followed by a \'rebound\' parasympathetic response and atrial mechanical dysfunction which may explain the propensity and temporal association between binge drinking and AF.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 May 2021; 331:100-105
Voskoboinik A, McDonald C, Chieng D, O'Brien J, ... Taylor AJ, Kistler PM
Int J Cardiol: 14 May 2021; 331:100-105 | PMID: 33548379
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Impact:
Abstract

Sequential dilation strategy in stent therapy of the aortic coarctation: A single centre experience.

Bambul Heck P, Fayed M, Hager A, Cesna S, ... Ewert P, Eicken A
Background
In our study, we sought to analyse the mid-term results after interventional aortic coarctation (CoA) stenting with sequential dilation of the stent.
Methods
The data of all 218 patients, who are above the age of 6 years and underwent CoA-stent implantation in our hospital, were retrospectively analysed on the rate of re-interventions, complications and arterial hypertension at a follow-up time of 31 months. To avoid any aortic complications, stents were deployed primarily not in full size and a second cardiac catheterisation for further dilatation was scheduled within 6-12 months after the stent implantation.
Results
The median peak invasive systolic pressure gradient declined significantly from 26.2 mmHg to 2.7 mmHg after stenting. There was one procedure related death due to an aortic rupture after stent implantation. There were in total 33 (15.1%) procedure-related complications including femoral artery complications, stent fracture and stent dislocation (in 9, 9 and 7 patients, respectively). In 85 patients a re-dilatation and in 25 patients a second stent-implantation was necessary at the first re-intervention. The systolic blood pressure declined significantly from 144 mmHg to 131 mmHg after stenting. The number of patients being normotensive changed from 18% before stenting to 78.5% after stenting with adjusted antihypertensive medication.
Conclusion
Aortic stenting is an effective means for CoA treatment. With sequential dilation of the stent, a very low rate of life-threatening procedural complications and mortality can be achieved. CoA stenting with proper antihypertensive medications results in better control of blood pressure.

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

Int J Cardiol: 14 May 2021; 331:82-87
Bambul Heck P, Fayed M, Hager A, Cesna S, ... Ewert P, Eicken A
Int J Cardiol: 14 May 2021; 331:82-87 | PMID: 33548378
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Impact:
Abstract

Real-world effectiveness and safety of sacubitril/valsartan in heart failure: A systematic review.

Proudfoot C, Studer R, Rajput T, Jindal R, ... Corda S, Senni M
Background
PARADIGM-HF demonstrated superiority of sacubitril/valsartan (sac/val) over enalapril in patients with heart failure with reduced ejection fraction (HFrEF). However, patients in clinical practice may differ in their characteristics and overall risk compared with patients in clinical trials, and additional outcomes can be observed in real world (RW). Hence, a systematic review was conducted to identify and describe RW data on sac/val.
Methods
RW studies evaluating the effects of sac/val in adult patients with HFrEF with a sample size ≥100 were identified via MEDLINE® and Embase® from 2015 to January 2020. Citations were screened, critically appraised and relevant data were extracted.
Results
A total of 68 unique studies were identified. Nearly half of the studies were conducted in Europe (n = 34), followed by the US (n = 15) and Asia (n = 11). Median follow-up period varied from 1 to 19 months. Mean age ranged between 48.7 and 79.0 years; patients were mostly male and in New York Heart Association (NYHA) functional class II/III, and mean left ventricular ejection fraction varied between 23%and 38%. Of studies performing comparisons, most reported superior efficacy of sac/val in reducing the risk of HF hospitalisations, all-cause hospitalisations, and all-cause mortality as compared to standard-of-care. Many studies reported significant improvements in NYHA functional class and reduction in biomarker levels post sac/val. Hypotension and hyperkalaemia were the most frequently reported adverse events.
Conclusions
This comprehensive overview of currently available RW evidence on sac/val complements the evidence from randomised controlled trials, substantiating its effectiveness in heterogeneous real-world HF populations.

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

Int J Cardiol: 14 May 2021; 331:164-171
Proudfoot C, Studer R, Rajput T, Jindal R, ... Corda S, Senni M
Int J Cardiol: 14 May 2021; 331:164-171 | PMID: 33545266
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Impact:
Abstract

Impact of right ventricular work and pulmonary arterial compliance on peak exercise oxygen uptake in idiopathic pulmonary arterial hypertension.

Messina CMS, Ferreira EVM, Singh I, Fonseca AXC, ... Oliveira RKF, Ota-Arakaki JS
Background
Pulmonary arterial hypertension (PAH) is associated with increased right ventricular (RV) afterload, RV dysfunction and decreased peak oxygen uptake (pVO2). However, the pulmonary hemodynamic mechanisms measured by exercise right heart catheterization (RHC) that contribute to reduced pVO2 in idiopathic PAH (IPAH) are not completely characterized. Therefore, we sought to evaluate the exercise RHC determinants of pVO2 in patients with IPAH.
Methods
519 consecutive patients with suspected and/or confirmed pulmonary hypertension were prospectively screened to identify 20 patients with IPAH. All IPAH patients were prospectively evaluated with resting and exercise RHC and cardiopulmonary exercise testing.
Results
85% of the patients were female; the median age was 34[29-42] years old. At peak exercise, mean pulmonary arterial (PA) pressure was 76 ± 17 mmHg, PA wedge pressure was 14 ± 5 mmHg, cardiac output (CO) was 5.7 ± 1.9 L/min, pulmonary vascular resistance was 959 ± 401 dynes/s/cm5 and PA compliance was 0.9[0.6-1.2] ml/mmHg. On univariate analysis, pVO2 positively correlated to peak CO, peak cardiac index, peak stroke volume index, peak RV stroke work index (RVSWI) and peak oxygen saturation. There was a negative correlation between pVO2 and Δ (rest to peak change) PA compliance. In age-adjusted multivariate model, peak RVSWI (Coefficient = 0.15, Beta = 0.63, 95% CI [0.07-0.22], p < 0.01) and ΔPA compliance (Coefficient = -2.51, Beta = -0.43, 95% CI [-4.34-(-0.68)], p = 0.01) had the best performance predicting pVO2 (R2 = 0.66).
Conclusions
In conclusion, a load dependent measurement of RV function (RVSWI) and the pulsatile component of RV afterload (ΔPA compliance) significantly influence pVO2 in IPAH, further highlighting the pivotal role of hemodynamic coupling to IPAH exercise capacity.

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

Int J Cardiol: 14 May 2021; 331:230-235
Messina CMS, Ferreira EVM, Singh I, Fonseca AXC, ... Oliveira RKF, Ota-Arakaki JS
Int J Cardiol: 14 May 2021; 331:230-235 | PMID: 33545265
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Impact:
Abstract

A plasma lipid signature predicts incident coronary artery disease.

Ottosson F, Emami Khoonsari P, Gerl MJ, Simons K, Melander O, Fernandez C
Background
Dyslipidemia is a hallmark of cardiovascular disease but is characterized by crude measurements of triglycerides, HDL- and LDL cholesterol. Lipidomics enables more detailed measurements of plasma lipids, which may help improve risk stratification and understand the pathophysiology of cardiovascular disease.
Methods
Lipidomics was used to measure 184 lipids in plasma samples from the Malmö Diet and Cancer - Cardiovascular Cohort (N = 3865), taken at baseline examination. During an average follow-up time of 20.3 years, 536 participants developed coronary artery disease (CAD). Least absolute shrinkage and selection operator (LASSO) were applied to Cox proportional hazards models in order to identify plasma lipids that predict CAD.
Results
Eight plasma lipids improved prediction of future CAD on top of traditional cardiovascular risk factors. Principal component analysis of CAD-associated lipids revealed one principal component (PC2) that was associated with risk of future CAD (HR per SD increment =1.46, C·I = 1.35-1.48, P < 0.001). The risk increase for being in the highest quartile of PC2 (HR = 2.33, P < 0.001) was higher than being in the top quartile of systolic blood pressure. Addition of PC2 to traditional risk factors achieved an improvement (2%) in the area under the ROC-curve for CAD events occurring within 10 (P = 0.03), 15 (P = 0.003) and 20 (P = 0.001) years of follow-up respectively.
Conclusions
A lipid pattern improve CAD prediction above traditional risk factors, highlighting that conventional lipid-measures insufficiently describe dyslipidemia that is present years before CAD. Identifying this hidden dyslipidemia may help motivate lifestyle and pharmacological interventions early enough to reach a substantial reduction in absolute risk.

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

Int J Cardiol: 14 May 2021; 331:249-254
Ottosson F, Emami Khoonsari P, Gerl MJ, Simons K, Melander O, Fernandez C
Int J Cardiol: 14 May 2021; 331:249-254 | PMID: 33545264
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Impact:
Abstract

The alcohol-induced cardiomyopathy: A cardiovascular magnetic resonance characterization.

Artico J, Merlo M, Asher C, Cannatà A, ... Lombardi M, Carr-White G
Background
Alcoholic cardiomyopathy(ACM) is part of the non-ischaemic dilated cardiomyopathy(NI-DCM) spectrum. Little is known about cardiovascular magnetic resonance(CMR) features in ACM patients. The aim of this study is to describe CMR findings and their prognostic impact in ACM patients.
Methods
Consecutive ACM patients evaluated in five referral CMR centres from January 2005 to December 2018 were enrolled. CMR findings and their prognostic value were compared to idiopathic NI-DCM(iNI-DCM) patients. The main outcome was a composite of death/heart transplantation/life-threatening arrhythmias.
Results
Overall 114 patients (52 with ACM and 62 with iNI-DCM) were included. ACM patients were more often males compared to iNI-DCM (90% vs 64%, respectively, p ≤ 0.001) and were characterized by a more pronounced biventricular adverse remodelling than iNI-DCM, i.e. lower LVEF (31 ± 12% vs 38 ± 11% respectively, p = 0.001) and larger left ventricular end-diastolic volume (116 ± 40 ml/m2 vs 67 ± 20 ml/m2 respectively, p < 0.001). Similarly to iNI-DCM, late gadolinium enhancement (LGE), mainly midwall, was present in more than 40% of ACM patients but, conversely, it was not associated with adverse outcome(p = 0.15). LGE localization was prevalently septal (87%) in ACM vs lateral in iNI-DCM(p < 0.05). Over a median follow-up of 42 months [Interquartile Range 24-68], adverse outcomes were similar in both groups(p = 0.67).
Conclusions
ACM represents a specific phenotype of NI-DCM, with severe morpho-functional features at the onset, but similar long-term outcomes compared to iNI-DCM. Despite the presence and pattern of distribution of LGE was comparable, ACM and iNI-DCM showed a different LGE localization, mostly septal in ACM and lateral in iNI-DCM, with different prognostic impact.

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

Int J Cardiol: 14 May 2021; 331:131-137
Artico J, Merlo M, Asher C, Cannatà A, ... Lombardi M, Carr-White G
Int J Cardiol: 14 May 2021; 331:131-137 | PMID: 33545263
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Impact:
Abstract

Diastolic dysfunction in women with ischemia and no obstructive coronary artery disease: Mechanistic insight from magnetic resonance imaging.

Samuel TJ, Wei J, Sharif B, Tamarappoo BK, ... Bairey Merz CN, Nelson MD
Background
Ischemia with no obstructive coronary artery disease (INOCA) is prevalent in women and is associated with increased risk of developing heart failure with preserved ejection fraction (HFpEF); however, the mechanism(s) contributing to this progression remains unclear. Given that diastolic dysfunction is common in women with INOCA, defining mechanisms related to diastolic dysfunction in INOCA could identify therapeutic targets to prevent HFpEF.
Methods
Cardiac MRI was performed in 65 women with INOCA and 12 reference controls. Diastolic function was defined by left ventricular early diastolic circumferential strain rate (eCSRd). Contributors to diastolic dysfunction were chosen a priori as coronary vascular dysfunction (myocardial perfusion reserve index [MPRI]), diffuse myocardial fibrosis (extracellular volume [ECV]), and aortic stiffness (aortic pulse wave velocity [aPWV]).
Results
Compared to controls, eCSRd was lower in INOCA (1.61 ± 0.33/s vs. 1.36 ± 0.31/s, P = 0.016); however, this difference was not exaggerated when the INOCA group was sub-divided by low and high MPRI (P > 0.05) nor was ECV elevated in INOCA (29.0 ± 1.9% vs. 28.0 ± 3.2%, control vs. INOCA; P = 0.38). However, aPWV was higher in INOCA vs. controls (8.1 ± 3.2 m/s vs. 6.1 ± 1.5 m/s; P = 0.045), and was associated with eCSRd (r = -0.50, P < 0.001). By multivariable linear regression analysis, aPWV was an independent predictor of decreased eCSRd (standardized β = -0.39, P = 0.003), as was having an elevated left ventricular mass index (standardized β = -0.25, P = 0.024) and lower ECV (standardized β = 0.30, P = 0.003).
Conclusions
These data provide mechanistic insight into diastolic dysfunction in women with INOCA, identifying aortic stiffness and ventricular remodeling as putative therapeutic targets.

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

Int J Cardiol: 14 May 2021; 331:1-7
Samuel TJ, Wei J, Sharif B, Tamarappoo BK, ... Bairey Merz CN, Nelson MD
Int J Cardiol: 14 May 2021; 331:1-7 | PMID: 33545261
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Impact:
Abstract

Long-term follow-up of patients with infective endocarditis in a tertiary referral center.

Tahon J, Geselle PJ, Vandenberk B, Hill EE, ... Janssens S, Herregods MC
Background
Infective endocarditis (IE) remains a severe disease with high mortality. Most studies report on short-term outcome while real world long-term outcome data are scarce. This study reports reinfection rates and mortality data during long-term follow-up.
Methods
A total of 270 patients meeting the modified Duke criteria for definite IE admitted to a tertiary care center between July 2000 and June 2007 were analyzed retrospectively. Early reinfection was defined as a new IE episode within 6 months; late reinfection as a new IE episode beyond 6 months follow-up.
Results
Median follow-up was 8.5 years. Early reinfection occurred in 10 patients (3.7%), late reinfection in 18 patients (6.7%). Staphylococci (39.7%) were the most frequent causative microorganisms, followed by Streptococci (30.0%) and Enterococci (17.8%). Independent predictors of any reinfection were heart failure (HR 3.02, 95% CI 1.42-6.41), peripheral embolization (HR 4.00, 95% CI 1.58-10.17) and implanted pacemakers (HR 3.43, 95% CI 1.25-9.36). Survival rates were 71.1%, 55.2% and 43.3% at respectively 1-, 5- and 10-years follow-up. Independent predictors for mortality were age (HR 1.03, 95% CI 1.01-1.04), diabetes mellitus (HR 2.24, 95% CI 1.46-3.45), hemodialysis (HR 2.70, 95% CI 1.37-5.29), heart failure (HR 1.64, 95% CI 1.19-2.26), stroke (HR 1.73, 95% CI 1.18-2.52), antimicrobial treatment despite surgical indication (HR 5.53, 95% CI 3.59-8.49) and non-Streptococci causative microorganisms (HR 1.84, 95% CI 1.28-2.64).
Conclusions
Contemporary mortality rates of infective endocarditis remain high, irrespective of reinfection. Heart failure, peripheral embolization and presence of a pacemaker were predictors of reinfection.

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

Int J Cardiol: 14 May 2021; 331:176-182
Tahon J, Geselle PJ, Vandenberk B, Hill EE, ... Janssens S, Herregods MC
Int J Cardiol: 14 May 2021; 331:176-182 | PMID: 33545260
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Impact:
Abstract

Non-immune risk predictors of cardiac allograft vasculopathy: Results from the U.S. organ procurement and transplantation network.

Fluschnik N, Geelhoed B, Becher PM, Schrage B, ... Schnabel RB, Magnussen C
Background
Cardiac allograft vasculopathy (CAV) remains a major long-term complication in heart transplant (HT) recipients related to increased mortality. We aimed to identify non-immune recipient- and donor-related risk factors for the development of CAV in HT patients.
Methods
40,647 recipients, prospectively enrolled from April 1995 to January 2019 in the Organ Procurement and Transplantation Network (OPTN), were analyzed after exclusion of pediatric patients, those with missing information on CAV, and re-transplantation. Multivariable-adjusted Cox regression analyses were performed to identify recipient- and donor-related risk factors for CAV. 5-year population attributable risk for classical cardiovascular risk factors was calculated to estimate the recipients\' CAV risk. Analyses were based on OPTN data (June 30, 2019).
Results
Of 40,647 post-transplant patients, 14,698 (36.2%) developed CAV with a higher incidence in males (37.3%) than in females (32.6%) (p < 0.001). The mean follow-up time was 68.2 months. In recipients, male sex, African American and Asian ethnicity, ischemic cardiomyopathy, body mass index and smoking were associated with CAV occurrence. In donors, older age, male sex, smoking, diabetes and arterial hypertension were related to CAV. Results remained fairly stable after analysis of different time periods. 5-year attributable CAV risk for classical cardiovascular risk factors was 9.1%.
Conclusions
In this large registry with known limitations concerning data completeness, CAV incidence was higher in males than in females. Next to male sex and donor age, the classical cardiovascular risk factors were related to incident CAV. Classical cardiovascular risk factors played only a minor role for the 5-year attributable CAV risk.

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

Int J Cardiol: 14 May 2021; 331:57-62
Fluschnik N, Geelhoed B, Becher PM, Schrage B, ... Schnabel RB, Magnussen C
Int J Cardiol: 14 May 2021; 331:57-62 | PMID: 33571561
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Impact:
Abstract

Cardiovascular magnetic resonance: What clinicians should know about safety and contraindications.

Barison A, Baritussio A, Cipriani A, De Lazzari M, ... Dellegrottaglie S, Working Group on Cardiac Magnetic Resonance of the Italian Society of Cardiology
Cardiovascular magnetic resonance (MR) is a multiparametric, non-ionizing, non-invasive imaging technique, which represents the imaging gold standard to study cardiac anatomy, function and tissue characterization. Faced with a wide range of clinical application, in this review we aim to provide a comprehensive guide for clinicians about MR safety, contraindications and image quality. Starting from the physical interactions of the static magnetic fields, gradients and radiofrequencies with the human body, we will describe the most common metal and electronic devices which are allowed (MR-safe), allowed under limited conditions (MR-conditional) or contraindicated (MR-unsafe). Moreover, some conditions potentially affecting image quality and patient comfort will be mentioned, including arrhythmias, claustrophobia, and poor breath-hold capacity. Finally, we will discuss the pharmacodynamics and pharmacokinetics of current gadolinium-based contrast agents, their contraindications and their potential acute and chronic adverse effects, as well as the safety issue concerning the use of vasodilating/inotropic agents in stress cardiac MR.

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

Int J Cardiol: 14 May 2021; 331:322-328
Barison A, Baritussio A, Cipriani A, De Lazzari M, ... Dellegrottaglie S, Working Group on Cardiac Magnetic Resonance of the Italian Society of Cardiology
Int J Cardiol: 14 May 2021; 331:322-328 | PMID: 33571560
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Impact:
Abstract

Rare variants in MTHFR predispose to occurrence and recurrence of pulmonary embolism.

Tan JS, Yan XX, Wu Y, Gao X, ... Hua L, Wang XJ
Background
Rare genetic variants play a critical role in unprovoked pulmonary embolism (PE). However, the known risk genes only account a small proportion of patients with PE. The objective of this study was to investigate the relationship between the rare variants of gene encoding methylenetetrahydrofolate reductase (MTHFR) and the initiation and long-term clinical outcomes of PE.
Methods
The rare variants of MTHFR were detected by whole exome sequencing of DNA from 258 unprovoked PE cases and 11,451 controls. Correlation of genotype and clinical phenotype and outcome were evaluated at baseline and after follow-up.
Results
MTHFR rare variants were found in 15 of 258 cases (5.81%) and 241 of 11,451 controls (2.10%), conferring 2.87-fold greater odds of the PE occurrence (OR = 2.87, 95% CI = 1.68-4.91, P = 5.6 × 10-5, chi-square test). The patients with MTHFR rare variants had higher plasma level of homocysteine than those without. During a follow-up of 3.0 years, a total of 84 events were identified. The recurrent PE (two or more events of PE) were significantly higher in patients carrying MTHFR rare variants (8/15, 53.3%) compared with those without (55/239, 23.0%) (P = 0.023).
Conclusion
We speculate that MTHFR rare variants may increase the occurrence and recurrence of PE.

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

Int J Cardiol: 14 May 2021; 331:236-242
Tan JS, Yan XX, Wu Y, Gao X, ... Hua L, Wang XJ
Int J Cardiol: 14 May 2021; 331:236-242 | PMID: 33571559
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Impact:
Abstract

Changes in strain parameters at different deterioration levels of left ventricular function: A cardiac magnetic resonance feature-tracking study of patients with left ventricular noncompaction.

Szűcs A, Kiss AR, Gregor Z, Horváth M, ... Merkely B, Vágó H
Background
There is a lack of cardiac MRI information on left ventricular (LV) strain and rotational parameters of left ventricular noncompaction (LVNC) patients with reduced ejection fraction (EF). Thus, we sought to use feature tracking (FT) to describe these changes at different levels of EF deterioration.
Methods
We included 31 adult LVNC patients with reduced LV EF (Group B, EF < 50%) without any comorbidities or concomitant cardiac diseases, 31 age- and sex-matched LVNC patients with good EF (Group A, EF > 50%) and 31 healthy controls. Group B was divided according to LV EF into two subgroups (Group B-1: EF 35-50%, Group B-2: EF < 35%). Their global longitudinal, circumferential (GCS), and radial (GRS) strains; LV segmental strains; LV apical and basal rotation values; and patterns and degree of LV dyssynchrony were measured.
Results
All of the global and mean segmental strain parameters were significantly worse in Groups B, B-1 and B-2 than in Group A and in the controls. The LV mechanical dispersion increased as LV EF decreased. The degree of apical rotation was the highest in the control group, almost the same in Group A and the lowest and in the reverse direction in Group B-2. A rotational pattern, clockwise-directed rigid body rotation (RBR), was found in 39% of the Group B patients, and a counterclockwise-directed RBR was found in 26% of the Group A patients.
Conclusions
The strain values and rotational parameters changed as the EF decreased. These changes affected the global LV, and we did not identify an LVNC-specific strain pattern.

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

Int J Cardiol: 14 May 2021; 331:124-130
Szűcs A, Kiss AR, Gregor Z, Horváth M, ... Merkely B, Vágó H
Int J Cardiol: 14 May 2021; 331:124-130 | PMID: 33577906
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Impact:
Abstract

Aortic enlargement in chronic obstructive pulmonary disease (COPD) and emphysema: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD study.

Fujikura K, Albini A, Barr RG, Parikh M, ... Gomes AS, Prince MR
Background
The prevalence of abdominal aortic aneurysm is high in chronic obstructive pulmonary disease (COPD) population. Emphysema involves proteolytic destruction of elastic fibers. Therefore, emphysema may also contribute to thoracic aorta dilatation. This study assessed aorta dilation in smokers stratified by presence of COPD, emphysema and airway thickening.
Methods
Aorta diameters were measured on 3D magnetic resonance angiography in smokers recruited from the Multi-Ethnic Study of Atherosclerosis (MESA), the Emphysema and Cancer Action Project (EMCAP), and the local community. COPD was defined by standard spirometric criteria; emphysema was measured quantitatively on computed tomography and bronchitis was determined from medical history.
Results
Participants (n = 315, age 58-79) included 150 with COPD and 165 without COPD, of whom 56% and 19%, respectively, had emphysema. Subjects in the most severe quartile of emphysematous change showed the largest diameter at all four aorta locations compared to those in the least severe quartiles (all p < 0.001). Comparing subjects with and without COPD, aorta diameters were larger in participants with severe COPD in ascending and arch (both p < 0.001), and abdominal aorta (p = 0.001). Chronic bronchitis and bronchial wall thickness did not correlate with aorta diameter. In subjects with emphysema, subjects with coexistence of COPD showed larger aorta than those without COPD in ascending (p = 0.003), arch (p = 0.002), and abdominal aorta (p = 0.04).
Conclusions
This study showed larger aorta diameter in subjects with COPD and severe emphysema compared to COPD related to chronic bronchitis or bronchial wall thickening.

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

Int J Cardiol: 14 May 2021; 331:214-220
Fujikura K, Albini A, Barr RG, Parikh M, ... Gomes AS, Prince MR
Int J Cardiol: 14 May 2021; 331:214-220 | PMID: 33587941
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Impact:
Abstract

Differential and prognostic value of cardiovascular magnetic resonance derived scoring algorithm in cardiac tumors.

Yue P, Xu Z, Wan K, Xie X, ... Sun J, Chen Y
Objectives
To establish a scoring algorithm based on cardiovascular magnetic resonance (CMR) parameters for differentiating between benign and malignant cardiac tumors and for predicting outcome.
Methods
Patients referred for CMR for suspected cardiac tumors were prospectively enrolled. Tumors were categorized as benign or malignant based on pathology, imaging, and clinical information. The CMR protocol included cine, T1-weighted, T2-weighted, first-pass perfusion, and late gadolinium enhancement (LGE) sequences. Variables independently associated with malignancy in the multivariable logistic analysis were used to construct the scoring algorithm, and receiver operating characteristic analyses were used to assess the ability to discriminate malignant from benign tumors. The ability of the score to predict outcome (all-cause mortality) was also assessed by Kaplan-Meier survival analysis.
Results
Among the 105 enrolled patients, 74 had benign and 31 had malignant tumors. In multivariable analysis, the independent predictors of malignant tumors were invasiveness (odds ratio, OR = 11.4, 2 points), irregular border (OR = 5.8, 1 point), and heterogenous LGE (OR 10.6, 2 points). The area under curves (AUC) of the scoring algorithm was 0.912 (cut-off score of 5) and showed significantly higher AUCs than individual variables (all P < 0.05) in differentiating benign and malignant tumors. After median follow-up of 18.2 months, mortality was significantly higher in patients with a score of 5 than in patients with score ≤ 4.
Conclusions
The scoring algorithm based on CMR-detected invasiveness, irregularity of border, and heterogenous LGE is an effective method for differentiating malignant from benign cardiac tumors and for predicting outcome.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 May 2021; 331:281-288
Yue P, Xu Z, Wan K, Xie X, ... Sun J, Chen Y
Int J Cardiol: 14 May 2021; 331:281-288 | PMID: 33582195
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Impact:
Abstract

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

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

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

Int J Cardiol: 30 Apr 2021; 328:146-151
Scheel A, Mirabel M, Nunes MCP, Okello E, ... Sable C, Beaton A
Int J Cardiol: 30 Apr 2021; 328:146-151 | PMID: 33186665
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Impact:
Abstract

Age-specific trends and outcomes of hospitalizations with acute heart failure in the United States.

Elbadawi A, Dang A, Elgendy IY, Thakker R, ... Khalife WI, Almustafa A
Objective
To analyze the age-specific temporal trends, in-hospital outcomes and readmissions for acute heart failure (HF).
Background
There is a paucity of data on the age-specific differences in the trends and outcomes of hospitalizations with acute HF.
Methods
The National Inpatients Sample database years 2002-2016 and the National Readmissions Database years 2013-2016 were used to identify primary hospitalizations for acute HF. We analyzed the age-specific temporal trends, in-hospital outcomes, and readmissions for acute HF.
Results
The annual rate of hospitalizations for acute HF declined from 456 per 100,000 people in 2002 to 356 per 100,000 people in 2016 (Ptrend < 0.001). The decline was observed among all age groups, except those aged 18-44 years. There was a decline in in-hospital mortality among all age groups, except for those aged 18-34 years. Compared with 18-34 years, adjusted in-hospital mortality was lower among 35-44 years (odds ratio 0.78, 95% confidence interval [CI] 0.74-0.82) and 45-54 years (OR 0.87; 95% CI 0.83-0.91) but higher among 55-64 years (OR 1.60; 95% CI 1.54-1.67) and ≥ 75 year (OR 2.54; 95% CI 2.44-2.64). Compared with 18-34 years, 30-day HF-related readmissions were significantly lower in older age groups (>34 years).
Conclusions
This nationwide contemporary analysis demonstrated a decline in the annual rates of hospitalizations with acute HF across all age categories except those aged 18-44 years. There was a reduction in rates of in-hospital mortality among middle-aged and older patients, but not in those aged 18-34. In-hospital mortality exhibited a dichotomous relationship with age. There was an inverse relationship between age and 30-days HF readmissions.

Published by Elsevier B.V.

Int J Cardiol: 30 Apr 2021; 330:98-105
Elbadawi A, Dang A, Elgendy IY, Thakker R, ... Khalife WI, Almustafa A
Int J Cardiol: 30 Apr 2021; 330:98-105 | PMID: 33609592
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Impact:
Abstract

Assessment of the left atrial appendage morphology in patients after ischemic stroke - The ASSAM study.

Dudzińska-Szczerba K, Michałowska I, Piotrowski R, Sikorska A, ... Kułakowski P, Baran J
Background
The ASSAM study was designed to evaluate the association between left atrial appendage (LAA) morphology and stroke risk in patients with atrial fibrillation (AF).
Methods
The study included 85 randomly chosen AF patients with acute ischemic stroke matched with 84 AF without stroke. All patients had left atrial (LA) computed tomography performed to analyze LAA anatomy.
Results
Patients in the stroke group had a larger LAA volume (10.22 [7.83-13.62] vs. 9.33 cm3 [7.33-11.47], p = 0.046], greater distance from LAA ostium to the first LAA bend (9.25 ± 3.85 vs. 7.23 ± 2.95 mm, p = 0.0002), and more frequently had round LAA ostium shape (11.8 vs. 1.2%, p = 0.005). According to a multivariable model, significant predictors of ischemic stroke were distance from LAA ostium to the first LAA bend (OR 1.202 [1.065-1.356], p = 0.003), LAA ostium round shape of (OR 16.813 [1.857-152.231], p = 0.012), LAA ostium surface area (OR 0.612 [0.457-0.819], p = 0.009), and cactus LAA morphology (OR 2.739 [1.176-6.380], p = 0.016). After adjusting for CHA2DS2-VASc score, only the distance from LAA ostium to the first LAA bend remained a significant risk factor for stroke (OR 1.154 [1.014-1.314], p = 0.03).
Conclusions
The distance from LAA ostium to the first bend of the LAA was independently associated with stroke risk in patients with AF. Whether this parameter may help improve identification of patients at risk of ischemic stroke, needs to be confirmed in larger studies.

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

Int J Cardiol: 30 Apr 2021; 330:65-72
Dudzińska-Szczerba K, Michałowska I, Piotrowski R, Sikorska A, ... Kułakowski P, Baran J
Int J Cardiol: 30 Apr 2021; 330:65-72 | PMID: 33524464
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Impact:
Abstract

Frequency of intracranial aneurysms and sub-arachnoid hemorrhage is significantly lesser in bicuspid aortic valve than aortic coarctation.

Vallabhajosyula S, Vallabhajosyula S, Yang LT, Rabinstein AA, Enriquez-Sarano M, Michelena HI
Background
Bicuspid aortic valve(BAV) is common. Some studies suggest that all BAV patients require screening for intracranial aneurysm(IA) in order to prevent sub-arachnoid hemorrhage(SAH). Aortic coarctation(CoA) carries high-risk of both IA and SAH. Using a nationally-representative population, we assessed the frequency of IA and SAH in admissions with BAV-without-CoA versus admissions with CoA(with or without BAV).
Methods
Between 2000 and 2016, adult admissions with a primary/secondary diagnosis of BAV and/or CoA were identified using the National Inpatient Sample. Admissions with traumatic SAH and inter-hospital transfers were excluded. Outcomes were frequency of IA and SAH, and in-hospital mortality in BAV-without-CoA versus CoA.
Results
In this 17-year period, 254,675 admissions met inclusion criteria and 236,930(93.0%) had BAV-without-CoA. BAV-with-CoA was present in 2846(1.1%) and isolated-CoA in 14,899(5.9%), for a total of 17,745(7%) with CoA. IA was noted in 405 admissions(0.2%) overall, BAV-without-CoA versus CoA having 293(0.1%) versus 112(0.6%), p < 0.001. SAH was noted in 910 admissions(0.4%) overall, with BAV-without-CoA versus CoA having 760(0.3%) versus 150(0.9%), p < 0.001.
Conclusions
In this study, BAV-without-CoA admissions had 0.1%(6-times lower than CoA) and 0.3%(3-times lower that CoA) IA and SAH, respectively, which is comparable to the general population. This suggests that BAV-without-CoA patients likely do not require routine surveillance for IA.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Apr 2021; 330:229-231
Vallabhajosyula S, Vallabhajosyula S, Yang LT, Rabinstein AA, Enriquez-Sarano M, Michelena HI
Int J Cardiol: 30 Apr 2021; 330:229-231 | PMID: 33516839
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Impact:
Abstract

Application of the heart failure meta-score to predict prognosis in patients with cardiac resynchronization defibrillators.

Theuns DAMJ, Schaer BA, Caliskan K, Hoeks SE, ... Yap SC, Alba AC
Background
The Heart Failure (HF) Meta-score may be useful in predicting prognosis in patients with primary prevention cardiac resynchronization defibrillators (CRT-D) considering the competing risk of appropriate defibrillator shock versus mortality.
Methods
Data from 648 consecutive patients from two centers were used for the evaluation of the performance of the HF Meta-score. The primary endpoint was mortality and the secondary endpoint was time to first appropriate implantable cardioverter-defibrillator (ICD) shock or death without prior appropriate ICD shock. Fine-Gray model was used for competing risk regression analysis.
Results
In the entire cohort, 237 patients died over a median follow-up of 5.2 years. Five-year cumulative incidence of mortality ranged from 12% to 53%, for quintiles 1 through 5 of the HF Meta-score, respectively (log-rank P < 0.001). Compared with the lowest quintile, mortality risk was higher in the highest quintile (HR 6.9; 95%CI 3.7-12.8). The HF Meta-score had excellent calibration, accuracy, and good discrimination in predicting mortality (C-statistic 0.76 at 1-year and 0.71 at 5-year). The risk of death without appropriate ICD shock was higher in risk quintile 5 compared to quintile 1 (sub HR 5.8; 95%CI 3.1-11.0, P < 0.001).
Conclusions
Our study demonstrated a good ability of the HF Meta-score to predict survival in HF patients treated with CRT-D as primary prevention. The HF Meta-score proved to be useful in identifying a subgroup with a significantly poor prognosis despite a CRT-D.

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

Int J Cardiol: 30 Apr 2021; 330:73-79
Theuns DAMJ, Schaer BA, Caliskan K, Hoeks SE, ... Yap SC, Alba AC
Int J Cardiol: 30 Apr 2021; 330:73-79 | PMID: 33516838
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Impact:
Abstract

Prognostic implications of prior contrast reaction in patients with emergency premedication before undergoing percutaneous coronary intervention.

Jha KK, El Hajj M, Nealy Z, Ofoma U, ... Thakur L, Blankenship JC
Background
Patients with iodinated contrast material (ICM) adverse reactions are at increased risk for breakthrough reactions. Previous studies suggest that the severity of a prior ICM adverse reaction corresponds to the severity of a repeat reaction.
Objective
We investigated whether the severity of prior ICM adverse reactions in patients receiving emergency premedication therapy prior to PCI predicts outcomes.
Methods
A retrospective observational study of percutaneous coronary intervention (PCI) encounters between January 1, 2005, and May 30, 2018, was conducted at Geisinger Medical Center. Patients with ICM adverse reactions premedicated with an emergency premedication regimen prior to PCI were included in the study. PCIs were stratified based on the severity of the index ICM adverse reactions; PCIs with a prior severe reaction were compared to PCIs with a prior mild-moderate reaction.
Results
We evaluated 604 PCI, of these, 144 (23.8%) had prior severe reactions and 460 (76.2%) had mild-to-moderate reactions. Nine patients had breakthrough reactions, of which seven were of the same or decreased severity in comparison to the index reactions. The overall breakthrough reactions occurred in 1 of 144 patients (0.7%) with an initial severe reaction and in 8 of 460 (1.7%) with an initial mild/moderate reaction (p = 0.69). Outcomes including length of hospital stay and 30-day mortality were similar for PCI with or without severe index ICM reactions.
Conclusion
Frequency and severity of breakthrough reaction and clinical outcomes in patients treated with emergency premedication regimen prior to PCI were independent of the severity of index ICM reactions.

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

Int J Cardiol: 30 Apr 2021; 330:30-34
Jha KK, El Hajj M, Nealy Z, Ofoma U, ... Thakur L, Blankenship JC
Int J Cardiol: 30 Apr 2021; 330:30-34 | PMID: 33516835
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Impact:
Abstract

Characterizing modifier genes of cardiac fibrosis phenotype in hypertrophic cardiomyopathy.

Xu F, Chen Y, Tillman KA, Cui Y, ... Lu L, Sun Y
Background
Clinical phenotypes of hypertrophic cardiomyopathy (HCM) vary greatly even among patients with the same gene mutations. This variability is largely regulated by unidentified modifier loci. The purpose of the study is to identify modifier genes for cardiac fibrosis-a major phenotype of HCM-using the BXD family, a murine cohort.
Methods
The relative severity of cardiac fibrosis was estimated by quantitation of cardiac collagen volume fraction (CCVF) across 66 members of the BXD family. Quantitative trait locus (QTL) mapping for cardiac fibrosis was done using GeneNetwork. Candidate modifier loci and genes associated with fibrosis were prioritized based on an explicit scoring system. Networks of correlation between fibrosis and cardiac transcriptomes were evaluated to generate causal models of disease susceptibility.
Results
CCVF levels varied greatly within this family. Interval mapping identified a significant CCVF-related QTL on chromosome (Chr) 2 in males, and a significant QTL on Chr 4 Mb in females. The scoring system highlighted two strong candidate genes in the Chr 2 locus-Nek6 and Nr6a1. Both genes are highly expressed in the heart. Cardiac Nek6 mRNA levels are significantly correlated with CCVF. Nipsnap3b and Fktn are lead candidate genes for the Chr 4 locus, and both are also highly expressed in heart. Cardiac Nipsnap3b gene expression correlates well with CCVF.
Conclusion
Our study demonstrated that candidate modifier genes of cardiac fibrosis phenotype in HCM are different in males and females. Nek6 and Nr6a1 are strong candidates in males, while Nipsnap3b and Fktn are top candidates in females.

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

Int J Cardiol: 30 Apr 2021; 330:135-141
Xu F, Chen Y, Tillman KA, Cui Y, ... Lu L, Sun Y
Int J Cardiol: 30 Apr 2021; 330:135-141 | PMID: 33529666
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Impact:
Abstract

Impact of delirium in acute cardiac care unit after transcatheter aortic valve replacement.

Luque T, Noriega FJ, McInerney A, Travieso A, ... Nombela-Franco L, Viana-Tejedor A
Background
Delirium is a cognitive disorder that commonly occurs during hospitalization in acute cardiac care units (ACCU), but its effect after transcatheter aortic valve replacement (TAVR) has not been well evaluated. The objective of this study is to determine the incidence, predictive factors and prognostic impact of delirium following TAVR.
Methods
A total of 501 consecutive patients admitted to an ACCU after TAVR were included. The Confusion Assessment Method was used to evaluate delirium during ACCU stay. Risk factors, preventive pharmacological treatment, peri-procedural characteristics and complications were assessed. Clinical events were recorded with a median follow-up of 24 months.
Results
The incidence of delirium after TAVR was 22.0% (n = 110). Previous cognitive impairment (OR 4.17; 95% CI 1.11-15.71; p = 0.035), peripheral arterial disease (OR 4.54; 95% CI 1.79-11.54; p = 0.001), the use of general anaesthesia (OR 2.55; 95% CI 1.32-4.90; p = 0.005), and prolonged mechanical ventilation (OR 18.86; 95% CI 1.85-192.58; p = 0.013) were significantly associated with the development of delirium. Patients with delirium had a greater hospital length of stay (7.5 [5.5-13.5] vs 5.6 [4.6-8.2] days, mean difference - 3.49; 95% CI -5.45 to -1.52; p < 0.001), and higher in-hospital (OR 2.68; 95% CI 1.02-6.99; p = 0.045), 1-year (HR 2.09; 95% CI 1.13-3.87; p = 0.018) and 2-year mortality (HR 1.94; 95% CI 1.12-3.34; p = 0.017).
Conclusions
Delirium is a frequent complication in patients admitted to ACCU after TAVR, and is associated with prolonged hospital stay and higher in-hospital and mid-term mortality.

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

Int J Cardiol: 30 Apr 2021; 330:164-170
Luque T, Noriega FJ, McInerney A, Travieso A, ... Nombela-Franco L, Viana-Tejedor A
Int J Cardiol: 30 Apr 2021; 330:164-170 | PMID: 33529663
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Impact:
Abstract

Clinical factors associated with massive pulmonary embolism and PE-related adverse clinical events.

Hariharan P, Giordano N, Muzikansky A, Kabrhel C
Background
Clinicians evaluating acute PE patients often have to identify risks for massive PE, a measure of hemodynamic instability and its consequence, massive PE related adverse clinical events (PEACE). We investigated the association of these risk factors with massive PE and PEACE in a consecutive PE cohort (n = 364).
Methods
Massive PE was defined as an acute central clot (proximal to the lobar artery) in a patient with right heart strain and systolic blood pressure ≤ 90 mg. PEACE was defined as any massive PE who died or required one or more of the following: ACLS, assisted ventilation, vasopressor use, thrombolytic therapy, or invasive thrombectomy, within seven days of PE diagnosis. Univariate and multivariate analysis assessing associations between the risk factors (age, gender, comorbidities, PE provoking risks, and whether the PE was felt to be idiopathic) and massive PE or PEACE were performed. Significance was determined at p < 0.05.
Results
Thirteen percent (n = 48) of patients presented with massive PE, and 9% (n = 32) had PEACE. In the final multivariate model, recent invasive procedure (RR = 7.4, p = 0.007), recent hospitalization (RR = 7.3, p = 0.002), and idiopathic PE (RR = 6.5, p = 0.003) were associated with massive PE. Only idiopathic PE (RR = 5.7, p = 0.005) was significantly associated with PEACE. No comorbidities or other PE provoking risks were associated with massive PE or PEACE.
Conclusions
As a take-home message, recent invasive procedure, recent hospitalization, and idiopathic PE were associated with massive PE, and only idiopathic PE was associated with PEACE. Simultaneously, comorbidities like age or chronic cardiopulmonary disease seem not to be associated with massive PE or PEACE.

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

Int J Cardiol: 30 Apr 2021; 330:194-199
Hariharan P, Giordano N, Muzikansky A, Kabrhel C
Int J Cardiol: 30 Apr 2021; 330:194-199 | PMID: 33535077
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Impact:
Abstract

Quality assurance of quantitative cardiac T1-mapping in multicenter clinical trials - A T1 phantom program from the hypertrophic cardiomyopathy registry (HCMR) study.

Zhang Q, Werys K, Popescu IA, Biasiolli L, ... Ferreira VM, Piechnik SK
Background
Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials.
Purpose
To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use.
Methods
MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and T2 dependency on temperature and phantom aging using phantom datasets from a single site over 4 years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites.
Results
T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R2 > 0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40 months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.54%), and was robust to temperature variations and phantom aging. Using the 95% confidence interval of the correlation model residuals as the tolerance range, we analyzed 390 ShMOLLI T1-maps and confirmed accurate sequence deployment in 90%(70/78) of QA scans across 28 multiple centers, and categorized the rest with specific remedial actions.
Conclusions
The proposed phantom QA for T1-mapping can assure correct method implementation and protocol adherence, and is robust to temperature variation and phantom aging. This QA program circumvents the need of frequent phantom replacements, and can be readily deployed in multicenter trials.

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

Int J Cardiol: 30 Apr 2021; 330:251-258
Zhang Q, Werys K, Popescu IA, Biasiolli L, ... Ferreira VM, Piechnik SK
Int J Cardiol: 30 Apr 2021; 330:251-258 | PMID: 33535074
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Impact:
Abstract

Serial assessment of de novo coronary lesions after drug-coated balloon treatment analyzed by intravascular ultrasound: A comparison between acute coronary syndrome and stable angina pectoris.

Funayama N, Kayanuma K, Sunaga D, Yamamoto T
Background
This study aimed to assess the serial changes in de novo coronary lesions, including acute coronary syndrome (ACS), treated with a drug-coated balloon (DCB).
Methods
In this retrospective single-center study, the intravascular changes in patients with de novo lesions treated with DCB were evaluated with serial intravascular ultrasound (IVUS) pre-procedure, post-procedure, and at follow-up. A two-dimensional IVUS measurement was performed with slices at 1 mm intervals in the treated lesion.
Results
This study comprised 40 lesions, including 27 lesions with stable angina pectoris (SAP) and 13 ACS. IVUS showed that the median vessel and lumen area increased significantly from pre-procedure to post-procedure and from post-procedure to follow-up. The median plaque area decreased significantly from pre-procedure to post-procedure and follow-up. The IVUS between ACS and SAP demonstrated that the total vessel volume and the total lumen volume increased, and the total atheroma volume decreased significantly from pre- to follow-up in both groups. The percent change in the lumen area increased, and the plaque area decreased significantly in ACS compared to SAP from pre- to post-procedure and follow-up.
Conclusion
The findings of this study suggest that DCB treatment for de novo coronary lesions in patients with ACS and SAP may maintain anatomical patency and increase lumen with positive vessel remodeling and regression of plaque.

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

Int J Cardiol: 30 Apr 2021; 330:35-40
Funayama N, Kayanuma K, Sunaga D, Yamamoto T
Int J Cardiol: 30 Apr 2021; 330:35-40 | PMID: 33539851
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Impact:
Abstract

Post-prandial effects of high-polyphenolic extra virgin olive oil on endothelial function in adults at risk for type 2 diabetes: A randomized controlled crossover trial.

Njike VY, Ayettey R, Treu JA, Doughty KN, Katz DL
Background
Effects of olive oil on cardiovascular risk have been controversial. We compared the effects of high-polyphenolic extra virgin olive oil (EVOO) and refined olive oil without polyphenols on endothelial function (EF) in adults at risk for Type 2 diabetes mellitus (T2DM).
Methods
Randomized, controlled, double-blind, crossover trial of 20 adults (mean age 56.1 years; 10 women, 10 men) at risk for T2DM (i.e., as defined by either prediabetes or metabolic syndrome) assigned to one of two possible sequence permutations of two different single dose treatments (50 mL of high-polyphenolic EVOO or 50 mL of refined olive oil without polyphenols), with 1-week washout. Participants received their olive oils in a smoothie consisting of ½ cup frozen blueberries and 1 cup (8 oz) low-fat vanilla yogurt blended together. Primary outcome measure was EF measured as flow-mediated dilatation. Participants were evaluated before and 2 h after ingestion of their assigned olive oil treatment.
Results
EVOO acutely improved EF as compared to refined olive oil (1.2 ± 6.5% versus -3.6 ± 3.8%; p = 0.0086). No significant effects on systolic or diastolic blood pressure were observed.
Conclusions
High-polyphenolic EVOO acutely enhanced EF in the study cohort, whereas refined olive oil did not. Blood pressure effects were not observed. Reports on the vascular effects of olive oil ingestion should specify the characteristics of the oil.
Clinical trial registration number
NCT04025281.

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

Int J Cardiol: 30 Apr 2021; 330:171-176
Njike VY, Ayettey R, Treu JA, Doughty KN, Katz DL
Int J Cardiol: 30 Apr 2021; 330:171-176 | PMID: 33548380
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Impact:
Abstract

Is there an optimal dose of cardiac rehabilitation in coronary artery disease patients?

Scherrenberg M, Janssen J, Lauwers A, Schreurs I, Swinnen M, Dendale P
Background
Many studies have shown that participation in cardiac rehabilitation reduces long-term morbidity and mortality after myocardial infarction. Therefore, both American and European evidence-based guidelines recommend cardiac rehabilitation. However, it is still unclear what the optimal dose of cardiac rehabilitation is.
Methodology
The study is a monocenter, retrospective cohort study. We identified patients with stable ischemic heart disease, who participated in at least one phase II center-based cardiac rehabilitation session between 2010 and 2015. A total of 609 patients were included in this study.
Results
We retrospectively reviewed the medical records of 609 patients. Statistically significant baseline differences between the four groups were observed for index coronary artery revascularization technique, age, dual antiplatelet therapy and smoking status. A total of number of 84 patients (13.8%) had a MACE in the four-year follow-up period. After adjustment for all significant predictors in the univariate analysis, patients who attended 36 or more sessions had a 47% lower risk of MACE (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.31 to 0.92), patients who attended 24 to 35 sessions had a 68% lower risk of MACE (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15 to 0.67), patients who attended 12 to 23 sessions had a 56% lower risk of MACE (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.21 to 0.92) than those who attended 1 to 11 sessions.
Conclusion
There is a clear clinical benefit from participating in more than 11 CR sessions. The best outcomes are achieved in patient who participated between 24 and 35 CR sessions. These results underline again the importance of improving participation and adherence to CR programmes in Europe.

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

Int J Cardiol: 30 Apr 2021; 330:7-11
Scherrenberg M, Janssen J, Lauwers A, Schreurs I, Swinnen M, Dendale P
Int J Cardiol: 30 Apr 2021; 330:7-11 | PMID: 33545262
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Impact:
Abstract

Responses to exercise training in patients with heart failure. Analysis by oxygen transport steps.

Legendre A, Moatemri F, Kovalska O, Balice-Pasquinelli M, ... Cristofini P, Iliou MC
Background
Exercise training (ET) increases exercise tolerance, improves quality of life and likely the prognosis in heart failure patients with reduced ejection fraction (HFrEF). However, some patients do not improve, whereas exercise training response is still poorly understood. Measurement of cardiac output during cardiopulmonary exercise test might allow ET response assessment according to the different steps of oxygen transport.
Methods
Fifty-three patients with HFrEF (24 with ischemic cardiomyopathy (ICM) and 29 with dilated cardiomyopathy (DCM) had an aerobic ET. Before and after ET program, peak oxygen consumption (VO2peak) and cardiac output using thoracic impedancemetry were measured. Oxygen convection (QO2peak) and diffusion (DO2) were calculated using Fick\'s principle and Fick\'s simplified law. Patients were considered as responders if the gain was superior to 10%.
Results
We found 55% VO2peak responders, 62% QO2peak responders and 56% DO2 responders. Four patients did not have any response. None baseline predictive factor for VO2peak response was found. QO2peak response was related to exercise stroke volume (r = 0.84), cardiac power (r = 0.83) and systemic vascular resistance (SVRpeak) (r = -0.42) responses. Cardiac power response was higher in patients with ICM than in those with DCM (p < 0.05). Predictors of QO2peak response were low baseline exercise stroke volume and ICM etiology. Predictors of DO2 response were higher baseline blood creatinine and prolonged training.
Conclusion
The analysis of the response to training in patients with HFrEF according to the different steps of oxygen transport revealed different phenotypes on VO2peak responses, namely responses in either oxygen convection and/or diffusion.

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

Int J Cardiol: 30 Apr 2021; 330:120-127
Legendre A, Moatemri F, Kovalska O, Balice-Pasquinelli M, ... Cristofini P, Iliou MC
Int J Cardiol: 30 Apr 2021; 330:120-127 | PMID: 33571565
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Impact:
Abstract

Behavioural determinants impacting the adoption rate of coronary physiology.

Demir OM, Schrieken C, Curio J, Rahman H
Background
Despite international revascularisation guidelines strongly recommending functional assessment of coronary artery stenosis using pressure-wire derived indices, the adoption rate of coronary physiology remains low.
Methods
An online questionnaire was designed to evaluate behavioural determinants impacting the adoption rate of coronary physiology. Factor analysis was performed to combine multiple items of a common behavioural domain into one explanatory factor. Regression analysis was performed to evaluate the influence of resulting factors on the variance of the coronary physiology adoption rate. Additionally, the influence of experience, demographics and provider structures was assessed.
Results
104 interventional cardiologists, from 21 countries, completed the questionnaire. Mean adoption rate of coronary physiology was 26.9%. Regression analysis revealed that factors ease-of-use (Coefficient = 0.58, p = 0.01), financial and/or time constraints (Coefficient = -0.22, p = 0.01) and knowledge about guideline recommendations (Coefficient = 0.21, p = 0.06) had the greatest influence on coronary physiology adoption rate variance (R2 = 0.3, p < 0.001), with ease-of-use and guideline recommendations positively influencing greater uptake and constraints influencing lesser uptake of adoption of coronary physiology.
Conclusion
Ease-of-use, financial and/or time constraints, and knowledge about guideline recommendations were the most relevant behavioural factors impacting the adoption rate of coronary physiology. Ease-of-use was identified as the most influential factor, highlighting the importance of cardiac catheterisation laboratory teams being adequately trained to perform coronary physiology assessment seamlessly.

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

Int J Cardiol: 30 Apr 2021; 330:12-14
Demir OM, Schrieken C, Curio J, Rahman H
Int J Cardiol: 30 Apr 2021; 330:12-14 | PMID: 33571564
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Impact:
Abstract

The impact of pulmonary valve replacement on pregnancy outcomes in women with tetralogy of Fallot.

Yamamura K, Duarte V, Karur GR, Graf J, ... Valente AM, Wald RM
Background
Pregnant women with repaired tetralogy of Fallot (rTOF) are at increased risk of adverse outcomes. Although pre-pregnancy pulmonary valve replacement (PVR) may be considered in some women to attenuate risk, published data to support this practice are lacking. Our objective was to explore the impact of pre-pregnancy PVR on pregnancy outcomes in rTOF.
Methods
Women with rTOF and cardiovascular magnetic resonance imaging (CMR) before and after pregnancy were included if CMR studies were completed within 3 years of pregnancy. Subjects were compared according to presence (+) or absence (-) of PVR at pre-pregnancy CMR. Pregnancy outcomes (cardiovascular, obstetric, and fetal/neonatal) were documented.
Results
Of the 29 study women identified, 7 were PVR+ and 22 were PVR-. Post-pregnancy, the PVR- group demonstrated interval increase in indexed right ventricular end-diastolic volumes (RVEDVi) (157 ± 28 versus 166 ± 33 ml/m2, p = 0.003) and end-systolic volumes (RVESVi) (82 ± 17 versus 89 ± 20 ml/m2, p = 0.003) as compared with pre-pregnancy, but no significant change in RV ejection fraction, RV mass, or left ventricular measurements. In the PVR+ group, there were no interval changes in RV measurements pre-versus post pregnancy. Interval rate of change in RVESVi of PVR- exceeded PVR+ women (+3.7 ± 5.0 versus -2.2 ± 5.0 ml/m2/year, p = 0.03). Pregnancy outcomes did not differ in PVR+ versus PVR- women.
Conclusions
Pregnancy outcomes did not differ according to PVR status in our cohort. While RV volumes remained unchanged in PVR+ women, interval RV dilation was observed in PVR- women. Additional study of a larger population with longer follow-up may further inform clinical practice regarding pre-pregnancy PVR.

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

Int J Cardiol: 30 Apr 2021; 330:43-49
Yamamura K, Duarte V, Karur GR, Graf J, ... Valente AM, Wald RM
Int J Cardiol: 30 Apr 2021; 330:43-49 | PMID: 33571563
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Impact:
Abstract

Aerobic exercise and inspiratory muscle training increase functional capacity in patients with univentricular physiology after Fontan operation: A randomized controlled trial.

Turquetto ALR, Dos Santos MR, Agostinho DR, Sayegh ALC, ... Jatene FB, Jatene MB
Background
The effect of exercise training and its mechanisms on the functional capacity improvement in Fontan patients (FP) are virtually unknown. This trial evaluated four-month aerobic exercise training and inspiratory muscle training on functional capacity, pulmonary function, and autonomic control in patients after Fontan operation.
Methods
A randomized controlled clinical trial with 42 FP aged 12 to 30 years and, at least, five years of Fontan completion. Twenty-seven were referred to a four-months supervised and personalized aerobic exercise training (AET) or an inspiratory muscle training (IMT). A group of non-exercise (NET) was used as control. The effects of the exercise training in peak VO2; pulmonary volumes and capacities, maximal inspiratory pressure (MIP); muscle sympathetic nerve activity (MSNA); forearm blood flow (FBF); handgrip strength and cross-sectional area of the thigh were analyzed.
Results
The AET decreased MSNA (p = 0.042), increased FBF (p = 0.012) and handgrip strength (p = 0.017). No significant changes in autonomic control were found in IMT and NET groups. Both AET and IMT increased peak VO2, but the increase was higher in the AET group compared to IMT (23% vs. 9%). No difference was found in the NET group. IMT group showed a 58% increase in MIP (p = 0.008) in forced vital capacity (p = 0.011) and forced expiratory volume in the first second (p = 0.011). No difference in pulmonary function was found in the AET group.
Conclusions
Both aerobic exercise and inspiratory muscle training improved functional capacity. The AET group developed autonomic control, and handgrip strength, and the IMT increased inspiratory muscle strength and spirometry.
Clinical trial registration
ClinicalTrials.gov Identifier: NCT02283255.

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

Int J Cardiol: 30 Apr 2021; 330:50-58
Turquetto ALR, Dos Santos MR, Agostinho DR, Sayegh ALC, ... Jatene FB, Jatene MB
Int J Cardiol: 30 Apr 2021; 330:50-58 | PMID: 33571562
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Impact:
Abstract

Clinical characteristics and outcomes in patients with echocardiographic left ventricular spontaneous echo contrast.

Liang D, Shi R, Zheng KI, Zhou X, ... Huang W, Shan P
Background
Spontaneous echo contrast (SEC) is a known precursor to thrombus formation and thromboembolic events. This study aims to demonstrate the clinical characteristics and outcomes of patients with left ventricular spontaneous echo contrast (LV-SEC).
Methods
Patients with consecutive echocardiogram performed from October 2009 to September 2019 were enrolled in this retrospective, single-center study. Those with LV-SEC were included, while patients complicated by left ventricular thrombus, with history of infective endocarditis, prosthetic valves, or lost to follow-up were excluded. The clinical endpoint was 1-year thromboembolic events (i.e. stroke and peripheral embolism).
Results
Among 417 patients (mean age 63.5 ± 14.7 years; 86.8% men) with LV-SEC, the incidence of 1-year embolism was 12.9%. In multivariate Cox proportional hazard model, significant risk factors for thromboembolic event were age [hazard ratio (HR) = 1.022, 95% confidence interval (CI): 1.000-1.045], atrial fibrillation (AF) (HR = 2.292, 95% CI: 1.237-4.244), hemoglobin (HR = 1.032, 95% CI: 1.017-1.047), left ventricular ejection fraction (LVEF) (HR = 1.021, 95% CI: 1.002-1.041), and anticoagulant therapy (HR = 0.310, 95% CI: 0.168-0.572). For patients with repeated measurements for echocardiography, D-dimer (HR = 1.137, 95% CI: 1.051-1.231), and LVEF (HR = 0.961, 95% CI: 0.928-0.996) were independently associated with the persistent LV-SEC.
Conclusion
The present study reported a high incidence of 1-year thromboembolic event in patients with LV-SEC. Age, AF, hemoglobin, LVEF were independent risk factors for 1-year embolism and a reduced risk of embolism was observed among patients with anticoagulation therapy. Additionally, D-dimer and LVEF are independently associated with the persistent LV-SEC.

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

Int J Cardiol: 30 Apr 2021; 330:245-250
Liang D, Shi R, Zheng KI, Zhou X, ... Huang W, Shan P
Int J Cardiol: 30 Apr 2021; 330:245-250 | PMID: 33577908
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Impact:
Abstract

Combining sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors in heart failure patients with reduced ejection fraction and diabetes mellitus: A multi-institutional study.

Hsiao FC, Lin CP, Tung YC, Chang PC, McMurray JJV, Chu PH
Background
Few studies investigated the combination of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and angiotensin receptor-neprilysin inhibitors (ARNIs) in patients with heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (T2DM).
Methods
During 2016 to 2018, patients with HFrEF and T2DM were identified from Chang Gung Research Database; a database deriving from the original electronic medical records of 7 hospitals in Taiwan. They were classified into four subgroups according to the medications received as follows: 1) SGLT2i and ARNI; 2) SGLT2i and no ARNI; 3) ARNI and no SGLT2i; and 4) no SGLT2i and no ARNI. We examined clinical and safety (hyperkalemia and acute renal dysfunction) outcomes over 1-year of follow-up.
Results
A total of 2312 patients were eligible for analysis, including 169, 285, 338, and 1520 in subgroups 1, 2, 3 and 4, respectively. There were large differences in baseline characteristics and treatments among subgroups. Subgroup 1 had the lowest rates of HF hospitalizations, all-cause death, and the composite of both, and subgroup 4 had the highest event rates. A similar pattern was observed for the safety outcomes. These differences were attenuated after adjusting for differences in baseline variables and therapy.
Conclusions
Treatment with a combination of SGLT2i and ARNI was well tolerated in diabetic patients with HFrEF and was associated with lower risk of heart failure hospitalization.

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

Int J Cardiol: 30 Apr 2021; 330:91-97
Hsiao FC, Lin CP, Tung YC, Chang PC, McMurray JJV, Chu PH
Int J Cardiol: 30 Apr 2021; 330:91-97 | PMID: 33587940
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Impact:
Abstract

Clinical management of young competitive athletes with premature ventricular beats: A prospective cohort study.

Di Florio A, Fusi C, Anselmi F, Cavigli L, ... Mondillo S, D\'Ascenzi F
Background
Premature ventricular beats (PVBs) are not an unusual finding and their interpretation is sometimes challenging. Unfortunately, few data on the characteristics of PVBs that correlate with the risk of an underlying heart disease are available in athletes.
Objectives
The aim of this prospective study was to investigate the diagnostic and prognostic value of PVBs characteristics in competitive athletes.
Methods
From a cohort of 1751 athletes evaluated at our sports cardiology centre, we enrolled 112 competitive athletes <40 years of age (mean age 21 ± 10 years) and with no known heart disease referred for PVBs. All athletes underwent physical examination, ECG, 12‑lead ambulatory ECG monitoring, exercise testing, and echocardiography. Further investigations including cardiac magnetic resonance were performed for abnormal findings at first-line evaluation or for specific PVBs characteristics.
Results
The majority (79%) of athletes exhibited monomorphic PVBs with a fascicular or infundibular pattern (common morphologies). A definitive diagnosis of cardiac disease was reached in 26 athletes (23% of the entire population) and correlated with uncommon PVBs morphology (p < 0.001) and arrhythmia complexity (p < 0.001). The number of PVBs/24-h was lower in athletes with cardiac disease than in those with normal heart (p < 0.05). During the follow-up a spontaneous reduction of PVBs and no adverse events were observed.
Conclusions
Infundibular and fascicular PVBs were the most common morphologies observed in athletes with ventricular arrhythmias referred for cardiological evaluation. Morphology and complexity of PVBs, but not their number, predicted the probability of an underlying disease. Athletes with PVBs and negative investigation showed a good prognosis.

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

Int J Cardiol: 30 Apr 2021; 330:59-64
Di Florio A, Fusi C, Anselmi F, Cavigli L, ... Mondillo S, D'Ascenzi F
Int J Cardiol: 30 Apr 2021; 330:59-64 | PMID: 33582199
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Impact:
Abstract

Treatment prescription, adherence, and persistence after the first hospitalization for heart failure: A population-based retrospective study on 100785 patients.

Scalvini S, Bernocchi P, Villa S, Paganoni AM, La Rovere MT, Frigerio M
Background
This study evaluates, in a real-world setting, to what extent the recommended therapies by international guidelines, are prescribed after a first hospitalization for heart failure (HF), and to analyse adherence and persistence, and the effect of treatment adherence on mortality and re-hospitalization.
Methods
From the Lombardy healthcare administrative database, we analysed patients discharged after their incident HF, from 2000 to 2012. Adherence was defined as the proportion of days covered (PDC) ≥80% adjusted for hospitalizations and persistence as the absence of discontinuation of therapy for >30 days. A logit model was used to determine the effect of patients\' adherence on mortality and readmissions.
Results
Of 100422 HF patients (52% males, age 75 ± 12 years), 86846 (87%) had a prescription for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACE/ARBs), 64135 (64%) for beta-blockers (BB), and 36893 (37%) for mineralocorticoid receptor antagonists (MRAs), as mono-, bi- or tri-therapy. In patients on monotherapy, PDC was 78 ± 22% for ACE/ARBs, 69 ± 29% for BB and 54 ± 29% for MRAs; in those on bi-therapy, PDC was 63 ± 31% for ACEI/ARBs+BB, 41 ± 29% for ACEI/ARBs+MRAs, and 40 ± 26% for MRAs+BB; for patients on tri-therapy, PDC was 42 ± 28%. Medication persistence was present in 47% of patients treated with ACEI/ARBs, in 35% of patients treated with BB and in 14% of patients treated with MRAs. Re-hospitalizations and in mortality were significantly reduced in adherent patients (p < 0.000).
Conclusions
Polypharmacy is associated with an increased rate of non-adherence and non-persistence in incident HF. Non-adherence is associated with an increased risk of mortality and re-hospitalizations.

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

Int J Cardiol: 30 Apr 2021; 330:106-111
Scalvini S, Bernocchi P, Villa S, Paganoni AM, La Rovere MT, Frigerio M
Int J Cardiol: 30 Apr 2021; 330:106-111 | PMID: 33582198
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Impact:
Abstract

Effectiveness and safety of infliximab in cardiac Sarcoidosis.

Bakker ALM, Mathijssen H, Azzahhafi J, Swaans MJ, ... Post MC, Grutters JC
Background
Immunosuppressive therapy in active cardiac sarcoidosis (CS) might prevent potential life-threatening complications. Infliximab (IFX) is a tumor necrosis factor alpha monoclonal antibody proven to be effective in refractory extracardiac sarcoidosis. It is sparsely used in CS, because of its association with worsening heart failure in prior studies. The goal of this study is to assess the effectiveness and safety of IFX in CS.
Methods and results
A retrospective, single center cohort study was performed in sarcoidosis patients treated with IFX based on a cardiac indication between January 2016 and March 2019. Patients received IFX intravenously at a dose of 5 mg/kg at week 0, 2, and subsequently every 4 weeks. After every six months, treatment response was evaluated within the multidisciplinary team using FDG-PET/CT, transthoracic echocardiography, biomarkers and device interrogation reports. Responder analysis definitions were based on; dosage of immunosuppressive drugs, improvement in functional class, left ventricular ejection fraction (LVEF) and SUVmax. Twenty-two patients were included (mean age 51.0 SD10.0 years, male 68.2%) with a mean follow-up of 18.9 months (6 to 44 months) of whom 18 (82%) were classified as responders. Median SUVmax on FDG-PET/CT decreased from SUVmax 5.2 [3.7-8.4] to 2.3 [1.4-2.3], p = 0.015. The target-to-background ratio decreased from 3.2 [2.1-5.1] to 1.0 [0.7-2.4], p = 0.002. The median left ventricular (LV) ejection fraction increased from 45.0% [34.0-60.0] to 55.0% [41.0-60.0], p = 0.02. The majority of patients (73%) experienced no side effects and no patients had worsening of heart failure.
Conclusion
In this pilot study, patients with refractory CS treated with infliximab, on top of standard of care, had a reduction in inflammation on FDG-PET/CT and an improvement in LV function, without serious adverse events.

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

Int J Cardiol: 30 Apr 2021; 330:179-185
Bakker ALM, Mathijssen H, Azzahhafi J, Swaans MJ, ... Post MC, Grutters JC
Int J Cardiol: 30 Apr 2021; 330:179-185 | PMID: 33582196
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Impact:
Abstract

Sacubitril-valsartan treatment is associated with decrease in central apneas in patients with heart failure with reduced ejection fraction.

Passino C, Sciarrone P, Vergaro G, Borrelli C, ... Emdin M, Giannoni A
Background
To assess the impact of sacubitril-valsartan on apneic burden in patients with heart failure with reduced ejection fraction (HFrEF), 51 stable HFrEF patients planned for switching from an ACE-i/ARB to sacubitril-valsartan were prospectively enrolled.
Methods and results
At baseline and after 6 months of treatment, all patients underwent echocardiography, 24-h cardiorespiratory monitoring, neurohormonal evaluation, and cardiopulmonary exercise testing. At baseline 29% and 65% of patients presented with obstructive and central apneas, respectively. After 6 months, sacubitril-valsartan was associated with a decrease in NT-proBNP, improvement in LV function, functional capacity and ventilatory efficiency. After treatment, the apnea-hypopnea index (AHI) decreased across the 24-h period (p < 0.001), as well as at daytime (p < 0.001) and at nighttime (p = 0.026), proportionally to baseline severity. When subgrouping according to the type of apneas, daytime, nighttime and 24-h AHI decreased in patients with central apneas (all p < 0.01). Conversely, in patients with obstructive apneas, the effect of drug administration was neutral at nighttime, with significant decrease only in daytime events (p = 0.007), mainly driven by reduction in hypopneas.
Conclusions
Sacubitril-valsartan on top of medical treatment is associated with a reduction in the apneic burden among a real-life cohort of HFrEF patients. The most marked reduction was observed for central apneas.

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

Int J Cardiol: 30 Apr 2021; 330:112-119
Passino C, Sciarrone P, Vergaro G, Borrelli C, ... Emdin M, Giannoni A
Int J Cardiol: 30 Apr 2021; 330:112-119 | PMID: 33581182
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Impact:
Abstract

Investigation of current models of care for genetic heart disease in Australia: A national clinical audit.

Austin R, Quinn MCJ, Afoakwah C, Metke-Jimenez A, ... Semsarian C, McGaughran J
Background
This sub-study of the Australian Genomics Cardiovascular Genetic Disorders Flagship sought to conduct the first nation-wide audit in Australia to establish the current practices across cardiac genetics clinics.
Method
An audit of records of patients with a suspected genetic heart disease (cardiomyopathy, primary arrhythmia, autosomal dominant congenital heart disease) who had a cardiac genetics consultation between 1st January 2016 and 31 July 2018 and were offered a diagnostic genetic test.
Results
This audit included 536 records at multidisciplinary cardiac genetics clinics from 11 public tertiary hospitals across five Australian states. Most genetic consultations occurred in a clinic setting (90%), followed by inpatient (6%) and Telehealth (4%). Queensland had the highest proportion of Telehealth consultations (9% of state total). Sixty-six percent of patients had a clinical diagnosis of a cardiomyopathy, 28% a primary arrhythmia, and 0.7% congenital heart disease. The reason for diagnosis was most commonly as a result of investigations of symptoms (73%). Most patients were referred by a cardiologist (85%), followed by a general practitioner (9%) and most genetic tests were funded by the state Genetic Health Service (73%). Nationally, 29% of genetic tests identified a pathogenic or likely pathogenic gene variant; 32% of cardiomyopathies, 26% of primary arrhythmia syndromes, and 25% of congenital heart disease.
Conclusion
We provide important information describing the current models of care for genetic heart diseases throughout Australia. These baseline data will inform the implementation and impact of whole genome sequencing in the Australian healthcare landscape.

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

Int J Cardiol: 30 Apr 2021; 330:128-134
Austin R, Quinn MCJ, Afoakwah C, Metke-Jimenez A, ... Semsarian C, McGaughran J
Int J Cardiol: 30 Apr 2021; 330:128-134 | PMID: 33581180
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Impact:
Abstract

Left Atrial Strain changes in patients with breast cancer during anthracycline therapy.

Laufer-Perl M, Arias O, Dorfman SS, Baruch G, ... Topilsky Y, Kapusta L
Background
Cardiotoxicity has become a significant adverse effect of cancer therapy, with Anthracyclines (ANT) in particular. There is a crucial need for new imaging techniques for the early subclinical detection of cardiotoxic effect. We aimed to evaluate left atrial strain (LAS) changes during ANT therapy and to assess the correlation between LAS and the routine echocardiographic diastolic parameters.
Methods and results
Data were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). All female patients with breast cancer, planned for ANT therapy were included. All patients underwent serial echocardiography exams including baseline LAS (before chemotherapy, T1) and shortly after the completion of ANT therapy (T3). LAS was assessed in 3 phases: Reservoir (LASr), Conduit (LASc) and Pump (LASp). Significant reduction in LASr was determined by either a relative reduction of >10% or an absolute value of <35%. From September 2016 to June 2019, 40 patients were evaluated with a mean Doxorubicin (type of ANT) dose of 237±13.24mg/m2. At T3, significant reduction in LASr was observed among 50% of the patients with a mean LASr reduction from 40.15 ± 6.83% to 36.04 ± 7.73% (p < 0.001). LASc showed significant reduction as well (p < 0.004) as opposed to LASp (p=0.076). Both LASr and LASc showed significant correlation to the routine diastolic parameters.
Conclusions
LASr and LASc reduction are frequent and occur early in the course of ANT therapy, showing significant correlation to the routine echocardiographic diastolic parameters, which may imply a role in the detection of early cardiotoxicity.

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

Int J Cardiol: 30 Apr 2021; 330:238-244
Laufer-Perl M, Arias O, Dorfman SS, Baruch G, ... Topilsky Y, Kapusta L
Int J Cardiol: 30 Apr 2021; 330:238-244 | PMID: 33581179
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Impact:
Abstract

Variability in utilization of diagnostic imaging tests in patients with symptomatic peripheral artery disease.

Derbas LA, Patel KK, Muskula PR, Wang J, ... Spertus JA, Smolderen KG
Aim
Imaging can help guide management in peripheral arterial disease (PAD) with symptoms refractory to medical treatment. However, there are no set guidelines to determine when physicians should seek further imaging in patients with PAD for the assessment of new, persistent or worsening symptoms. This study describes the rates and variability in non-invasive and invasive imaging for patients presenting to vascular specialty clinics for symptomatic PAD.
Methods
Patients (n=1,275) with a new PAD diagnosis or exacerbation of PAD symptoms were enrolled from 16 vascular clinics. Hierarchical logistic regression models were used to estimate the referral rates for 1) non-invasive and 2) invasive imaging tests, after adjusting for patient demographics, disease characteristics, PAQ summary score, PAD performance measures and country. Median Odds Ratios (MOR) were calculated to examine the variability across sites and providers.
Results
Mean ABI was 0.67 ± 0.19. There were 690 (54.1%) patients who had imaging, of which 62 (9.0%) had invasive imaging. Imaging rates ranged from 8.6% to 98.6% across sites. The MOR for use of imaging for site was 3.36 (p < 0.001) and provider 3.49 (p < 0.001). The variability was explained primarily by (R2 = 29%) country followed by patient-level factors, provider and lastly site (R2 = 17%, 14%, and 13%, respectively).
Conclusion
There is wide variation in the use of imaging for patients presenting with new onset or recent exacerbations of their PAD. Country, followed by provider and site, were most strongly associated with this variability after adjusting for patient characteristics.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Apr 2021; 330:200-206
Derbas LA, Patel KK, Muskula PR, Wang J, ... Spertus JA, Smolderen KG
Int J Cardiol: 30 Apr 2021; 330:200-206 | PMID: 33581177
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Impact:
Abstract

Evaluation of twelve formulas for LDL-C estimation in a large, blinded, random Italian population.

Piani F, Cicero AFG, Ventura F, Dormi A, ... D\'Addato S, BLIP Study Group
Background:
and aims
Low-density lipoprotein-cholesterol (LDL-C) is the major determinant of cardiovascular disease (CVD) burden. Being the direct assays time consuming, expensive, not fully standardized and not worldwide available, indirect formulas represent the most used laboratory estimation of LDL-C. In this study we analyzed the accuracy of twelve formulas for LDL-C estimation in an Italian population of 114,774 individuals.
Methods
All lipid samples were analyzed using direct homogeneous assay. The population was divided into various subgroups based on triglycerides and directly dosed LDL-C (D-LDL) levels. Twelve formulas (Friedewald, DeLong, Hata, Hattori, Puavillai, Anandaraja, Ahmadi, Chen, Vujovic, de Cordova, Martin, and Sampson) were compared in terms of their mean absolute deviations and the correlation and concordance of their estimated LDL-C with the respective D-LDL values.
Results
LCL-C measured by Friedewald formula and direct assay differed by more than 9 mg/dL. For D-LDL>115 mg/dl, we observed a concordance rate of only 55% between Friedewald and the respective D-LDL values. For TG<250 mg/dl, the proportion of reclassification between the different formulas and D-LDL was 14.1% with Vujovic, 14.4% Sampson, 15.9% DeLong, 16.5% Puavilai, 19.9% Martin, 21.9% Friedewald, 23.5% Chen, 29% Anandaraja, 31.1% Ahmadi, 31.5% Hata, 33.2% Hattori, and 44.4% with De Cordova formula.
Conclusions
Our study compared for the first time 12 different LDL-C formulas on a Southern European population of more than 100,000 people. \'Several formulas showed better accuracy compared to Friedewald. Sampson, Martin and Vujovic resulted the most accurate formulas.

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

Int J Cardiol: 30 Apr 2021; 330:221-227
Piani F, Cicero AFG, Ventura F, Dormi A, ... D'Addato S, BLIP Study Group
Int J Cardiol: 30 Apr 2021; 330:221-227 | PMID: 33581176
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Impact:
Abstract

Cardiovascular disease-specific mortality in 270,618 patients with non-small cell lung cancer.

Sun JY, Zhang ZY, Qu Q, Wang N, ... Zhang CY, Wang RX
Background
This study aimed to investigate the trend of cardiovascular disease (CVD)-specific mortality in patients with non-small cell lung cancer (NSCLC) and identify prognostic factors for CVD-specific death in stage NSCLC patients.
Methods
In this study, 270,618 NSCLC patients were collected from the Surveillance, Epidemiology, and End Results database. CVD- and NSCLC-specific cumulative mortality and proportion of death were calculated and graphically displayed to describe the probability of specific endpoints. Prognostic factors for CVD-specific mortality were evaluated by cause-specific hazard ratios (HR) with 95% confidence intervals (CI) using the competing risk model with non-cardiovascular death as competing risks.
Results
Among all competing causes of death, lung cancer resulted in the highest cumulative mortality, followed by CVDs and other causes. In the proportion of cause-specific death, heart diseases accounted for approximately 5.3% of the total death, only secondary to primary cancer. In all three stages, higher age, squamous cell carcinoma, and no-or-unknown chemotherapy and/or radiotherapy were associated with a higher risk of CVD-specific death, while surgery treatment seemed to be a protective factor. Female gender was statistically related to CVD-specific death in stage I and III patients with HRs of 0.84 (0.78-0.91) and 0.84 (0.77-0.93), respectively. Interestingly, right-sided laterality was correlated with lower CVD-specific mortality with HR of 0.82 (0.74-0.90) in stage III.
Conclusions
This study illustrated the historical trend of CVD-specific death in NSCLC patients and assesses potential prognostic risk factors, highlighting the involvement of cardio-oncology teams in cancer treatment to provide optimal comprehensive care and long-term surveillance for cancer patients.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Apr 2021; 330:186-193
Sun JY, Zhang ZY, Qu Q, Wang N, ... Zhang CY, Wang RX
Int J Cardiol: 30 Apr 2021; 330:186-193 | PMID: 33581175
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Impact:
Abstract

Infective endocarditis in patients with aortic grafts.

García-Arribas D, Olmos C, Vilacosta I, Perez-García CN, ... San Román JA, Maroto L
Background
Infective endocarditis (IE) in patients with a valve-tube ascending aortic graft (AAG) is a rare entity with a challenging diagnosis and treatment. This study describes the clinical features, diagnosis and outcome of these patients.
Methods
Between 1996 and 2019, 1654 episodes of IE were recruited in 3 centres, of which 37 patients (2.2%) had prosthetic aortic valve and AAG-IE (21 composite valve graft, 16 supracoronary graft) and conformed our study group.
Results
Patients with aortic grafts were predominantly male (91.9%) and the mean age was 67.7 years. Staphylococci were the most frequently isolated microorganisms (32%). Viridans group streptococci were only isolated in patients with composite valve graft. TEE was positive in 89.2%. PET/CT was positive in all 15 patients in whom it was performed. Surgical treatment was performed in 62.2% of patients. In-hospital mortality was 16.2%. Heart failure and the type of infected graft (supracoronary aortic graft) were associated with mortality. Mortality among operated patients was 21.7%. Interestingly, 14 patients received antibiotic therapy alone, and only one died. Mortality was lower among patients with a composite valve graft compared to those with a supracoronary graft (4.8% vs 31.3%; p = 0.03).
Conclusions
In patients with AAG and prosthetic aortic valve IE, mortality is not higher than in other patients with prosthetic IE. Multimodality imaging plays an important role in the diagnosis and management of these patients. Heart failure and the type of surgery were risk factors associated with in-hospital mortality. Although surgical treatment is usually recommended, a conservative management might be a valid alternative treatment in selected patients.

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

Int J Cardiol: 30 Apr 2021; 330:148-157
García-Arribas D, Olmos C, Vilacosta I, Perez-García CN, ... San Román JA, Maroto L
Int J Cardiol: 30 Apr 2021; 330:148-157 | PMID: 33592240
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Impact:
Abstract

Estimating the causal effect of BMI on mortality risk in people with heart disease, diabetes and cancer using Mendelian randomization.

Jenkins DA, Wade KH, Carslake D, Bowden J, ... Sperrin M, Rutter MK
Background
Observational data have reported that being overweight or obese, compared to being normal weight, is associated with a lower risk for death - the \"obesity paradox\". We used Mendelian randomization (MR) to estimate causal effects of body mass index (BMI) on mortality risks in people with coronary heart disease (CHD), type 2 diabetes mellitus (T2DM) or malignancy in whom this paradox has been often reported.
Methods
We studied 457,746 White British UK Biobank participants including three subgroups with T2DM (n = 19,737), CHD (n = 21,925) or cancer (n = 42,612) at baseline and used multivariable-adjusted Cox models and MR approaches to describe relationships between BMI and mortality risk.
Results
Observational Cox models showed J-shaped relationships between BMI and mortality risk including within disease subgroups in which the BMI values associated with minimum mortality risk were within overweight/obese ranges (26.5-32.5 kg/m2). In all participants, MR analyses showed a positive linear causal effect of BMI on mortality risk (HR for mortality per unit higher BMI: 1.05; 95% CI: 1.03-1.08), also evident in people with CHD (HR: 1.08; 95% CI: 1.01-1.14). Point estimates for hazard ratios across all BMI values in participants with T2DM and cancer were consistent with overall positive linear effects but confidence intervals included the null.
Conclusion
These data support the idea that population efforts to promote intentional weight loss towards the normal BMI range would reduce, not enhance, mortality risk in the general population including, importantly, individuals with CHD.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Apr 2021; 330:214-220
Jenkins DA, Wade KH, Carslake D, Bowden J, ... Sperrin M, Rutter MK
Int J Cardiol: 30 Apr 2021; 330:214-220 | PMID: 33592239
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Impact:
Abstract

Cardiac conduction abnormalities in patients with degenerated bioprostheses undergoing transcatheter aortic valve-in-valve implantations and their impact on long-term outcomes.

Stankowski T, Mangner N, Linke A, Aboul-Hassan SS, ... Fritzsche D, Perek B
Background
The relationship between preoperative cardiac conduction abnormalities (CCA) and long-term outcomes after transcatheter aortic valve-in-valve implantation (TAVI-VIV) remains unclear. The aim of the study was to evaluate the effects of preoperative CCA on mortality and morbidity after TAVI-VIV and to estimate the impact of new-onset CCA on postoperative outcomes.
Methods
Between 2011 and 2020, 201 patients with degenerated aortic bioprostheses were qualified for TAVI-VIV procedures in two German heart centers. Cases with previously implanted permanent rhythm-controlling devices were excluded (n = 53). A total of 148 subjects met the eligibility criteria and were divided into 2 study groups according to the presence of preexisting CCA (CCA (n = 84) and non-CCA (n = 64), respectively). Early and late mortality and morbidity were evaluated. Follow-up functional status was assessed according to New York Heart Association (NYHA) classification.
Results
There were no procedural deaths. TAVI-VIV related new-onset CCAs were observed in 35.8% patients. The 30-day permanent pacemaker implantation rate was 1.6% in non-CCA vs 9.5% in CCA group (p = 0.045). Preexisting right bundle-branch block (OR:5.01; 95%CI, 1.05-23.84) and first-degree atrioventricular block (OR:4.55; 95%CI, 1.10-18.73) were independent predictors of new pacemaker implantation. One-year and five-year probability of survival were comparable in CCA and non-CCA groups: 90.3% vs 91.8% and 68.2% vs 74.3%, respectively. Surviving patients with preexisting and new-onset CCA had a worse functional status according to NYHA classification at follow-up.
Conclusion
Preexisting and new-onset postoperative CCAs did not affect early and late mortality after TAVI-VIV procedures, however, they may have a negative impact on late functional status.

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

Int J Cardiol: 30 Apr 2021; 330:16-22
Stankowski T, Mangner N, Linke A, Aboul-Hassan SS, ... Fritzsche D, Perek B
Int J Cardiol: 30 Apr 2021; 330:16-22 | PMID: 33592238
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Impact:
Abstract

Prognostic value of longitudinal strain and ejection fraction in Friedreich\'s ataxia.

Legrand L, Heuze C, Diallo A, Monin ML, ... Durr A, Pousset F
Background
Friedreich\'s ataxia (FA) is a rare autosomal recessive mitochondrial disease most commonly due to a triplet repeat expansion guanine-adenine-adenine (GAA) in the FXN gene. Cardiac disease is the major cause of death, patients with reduced left ventricular ejection fraction (LVEF) having the worse prognosis. Longitudinal strain (LS) appeared to be a better predictor of outcome than LVEF in different diseases. We compared the prognostic value of LS measured from the 4 chambers view to LVEF.
Methods
From 2003 to 2017 consecutive patients with FA were included and LS analysis was retrospectively performed.
Results
We studied 140 patients, with a median age of 34 (26-41) years (Q1-Q3) with age at onset of 14 (11-19) years and GAA repeats on the shorter allele of 600 (467-783) pb. Mean LS was 19.9 ± 5.0% and LVEF 64 ± 8%. After a mean follow-up of 7.4 ± 3.9 years, 14 patients died. In univariate Cox analysis, all-cause mortality was associated with: LS (HR 0.83; 95%CI, 0.75-0.91, p = 0.0002), LVEF (HR 0.30; 95%CI, 0.19-0.49, p < 0.0001), GAA repeats on the shorter allele (HR 1.29; 95%CI, 1.10-1.51, p = 0.002), age at onset (HR 0.87; 95%CI, 0.77-0.98, p = 0.018), LVSystolic Diameter (HR 1.17; 95%CI, 1.09-1.26, p < 0.0001), LVMass index (HR 1.02; 95%CI, 1.00-1.04, p = 0.027), and LVDiastolic Diameter (HR1.12; 95%CI, 1.01-1.23, p = 0.028). In multivariate analysis, LVEF was the only independent predictor of mortality (HR 0.41; 95%CI, 0.23-0.74, p = 0.0029).
Conclusion
In FA, LS was not an independent predictor of mortality, LVEF remained the only independent predictor in the present study.

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

Int J Cardiol: 30 Apr 2021; 330:259-265
Legrand L, Heuze C, Diallo A, Monin ML, ... Durr A, Pousset F
Int J Cardiol: 30 Apr 2021; 330:259-265 | PMID: 33592237
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Impact:
Abstract

Comparison of the effect of Morphine and Fentanyl in patients with acute coronary syndrome receiving Ticagrelor - The COMET (Comparison Morphine, Fentayl and Ticagrelor) randomized controlled trial.

Senguttuvan NB, Suman F, Paneerselvam T, Malepati B, ... Baber U, Karthikeyan G
Introduction
Dual antiplatelet therapy (DAPT) remains the cornerstone of acute coronary syndrome (ACS) management, and ticagrelor is one of the commonly used second antiplatelet agents. There is some evidence to suggest that morphine may reduce the antiplatelet effect of ticagrelor.
Methods and results
In a single-center, randomized controlled trial, we compared the effect of morphine and fentanyl on platelet aggregation (PA) among patients with ACS treated with ticagrelor. Platelet aggregation was studied by automated light transmittance aggregometry (LTA) at baseline, and at 2 h after ticagrelor loading. The primary outcome was the difference in the maximal inhibition of platelet aggregation [IPA(%)] between the groups at 2 h. Pain relief, and drug-related adverse events were secondary outcomes. Of 136 patients randomized, 70 received fentanyl and 66 received morphine. At baseline, the median (IQR) platelet aggregation [61.35% (54.6 to 70) Vs. 58.8% (52.7 to 72.9)] were comparable between the groups. There was no statistically significant difference between the fentanyl and the morphine groups in IPA at 2-h [85.88%(64.65-98.16) and 81.93%(44.2-98.03), p = 0.09]. However, morphine use was independently associated with a PA of >30% at 2 h (p < 0.009). There was no difference in adverse events.
Conclusion
In patients with ACS, there was no significant difference between the use of fentanyl or morphine on the effect of ticagrelor on PA. (CTRI/2018/04/013423).

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

Int J Cardiol: 30 Apr 2021; 330:1-6
Senguttuvan NB, Suman F, Paneerselvam T, Malepati B, ... Baber U, Karthikeyan G
Int J Cardiol: 30 Apr 2021; 330:1-6 | PMID: 33600846
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Impact:
Abstract

Right ventricular strain in Anderson-Fabry disease.

Lillo R, Graziani F, Panaioli E, Mencarelli E, ... Lanza GA, Crea F
Background
2D speckle tracking echocardiography (2DSTE) is superior to standard echocardiography in the assessment of subtle right ventricle (RV) systolic dysfunction. In this study we aimed to: 1) test the hypothesis that 2DSTE may unveil subtle RV systolic dysfunction in patients with Fabry disease; 2) investigate whether the physiologic difference between the 3-segment (RV-FWS) and the 6-segment (RV-GLS) RV strain (∆RV strain) is preserved in Fabry patients.
Methods and results
Standard echocardiography and 2DSTE were performed in 49 Fabry patients and 49 age- and sex-matched healthy controls. Fabry patients were divided in two groups according to the presence/absence of left ventricular hypertrophy (LVH+: left ventricular wall thickness > 12 mm, 49% of total Fabry patients). RV systolic function assessed by standard echocardiography was normal in the majority of Fabry patients (92%) while RV-GLS and RV-FWS were impaired in about 40%. RV-GLS and RV-FWS were significantly worse in patients LVH+ vs LVH- and vs controls (RV-GLS: LVH+ vs LVH-: -18.4 ± -4.3% vs -23.8 ± -3.1% p<0.001; LVH+ vs controls: -18.4 ± -4.3% vs -23.9 ± -2.8% p<0.001; RV-FWS: LVH+ vs LVH-: -21.8 ± -5.3% vs -26.7 ± -3.8% p = 0.002, LVH+ vs controls -21.8 ± -5.3% vs -26.8 ± -3.9% p<0.001). No difference was found between LVH- patients and controls in both RV-GLS (p = 0.65) and RV-FWS (p = 0.79). ∆RV strain was similar among the groups.
Conclusions
In Fabry cardiomyopathy impaired RV-GLS and RV-FWS is a common finding, while RV strain is preserved in Fabry patients without overt cardiac involvement. The physiologic difference between RV-FWS and RV-GLS is maintained in Fabry patients, regardless of the presence of cardiomyopathy.

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

Int J Cardiol: 30 Apr 2021; 330:84-90
Lillo R, Graziani F, Panaioli E, Mencarelli E, ... Lanza GA, Crea F
Int J Cardiol: 30 Apr 2021; 330:84-90 | PMID: 33600844
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Impact:
Abstract

Transcatheter aortic valve replacement performed with selective telemetry monitoring: A prospective study.

Akodad M, Aldhaheri E, Marin G, Roubille F, ... Cayla G, Leclercq F
Background
Telemetry monitoring (TM) with or without intensive care unit (ICU) admission is the standard of care after Transcatheter aortic valve replacement (TAVR). Regarding to improvements of the technique and procedural results, TM may be considered only in selected patients. We aimed to confirm feasibility and safety of selective TM in patients undergoing TAVR.
Methods
We prospectively evaluated 449 consecutive patients undergoing TAVR. Patients were transferred to general cardiology ward (GCW) without TM after the procedure when stable clinical state, transfemoral access, no baseline right bundle branch block (RBBB), left ventricular ejection fraction (LVEF) > 40%, and no complication including any electrocardiogram (ECG) change within 1 h after the procedure (\"low-risk\" group). Others patients were considered for TM in ICU (\"high-risk\" group). The primary endpoint evaluated in-hospital major adverse events after unit admission according to VARC-2 criteria.
Results
The mean age was 81.8 ± 7.5 years and mean EuroSCORE II was 7.5 ± 4.8%. In total, 116 patients (25.8%) were considered as \"low-risk\" patients and 163 patients (36.3%) were referred to GCW, including those with immediate pacemaker implantation. A total of 96 patients (21.3%) reached the primary endpoint including mainly conductive disorders (12.8%). No major adverse events, particularly no late severe conductive disorder, occurred in the \"low-risk\" group (negative predictive value of 100%). Baseline RBBB (p < 0.01), LVEF < 40% (p = 0.02) and \"high-risk\" group (p < 0.01) were predictive of outcomes.
Conclusions
Using rigorous periprocedural selection criteria, patients\' admission in GCW without TM can be routinely and safely performed in 1/3 of patients after TAVR.

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

Int J Cardiol: 30 Apr 2021; 330:158-163
Akodad M, Aldhaheri E, Marin G, Roubille F, ... Cayla G, Leclercq F
Int J Cardiol: 30 Apr 2021; 330:158-163 | PMID: 33621627
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Impact:
Abstract

Ideal cardiovascular health in women with systemic lupus erythematosus: Association with arterial stiffness, inflammation, and fitness.

Hernández-Martínez A, Gavilán-Carrera B, Vargas-Hitos JA, Morillas-de-Laguno P, ... Sabio JM, Soriano-Maldonado A
Background
Systemic Lupus Erythematosus (SLE) is closely related to cardiovascular morbidity and mortality. We aimed to examine the association of ideal cardiovascular health (ICH) with arterial stiffness, inflammation, and physical fitness in women with SLE.
Methods
This cross-sectional study included 76 women with SLE (age 43.4±13.8 years old). Ideal levels of 7 health metrics (smoking, body mass index, physical activity, healthy diet, blood pressure, cholesterol, and glucose) were used to define the ICH score (ranging from 0 to 7 ideal metrics) and the ICH status ( defined as presenting ≥4 ideal metrics). Arterial stiffness was measured through pulse wave velocity (PWV) and inflammation through serum high sensitivity C-reactive protein (hs-CRP). Cardiorespiratory fitness (CRF) was measured by 6-min walk test (6MWT), and Siconolfi step test and muscular strength by handgrip strength and 30-s chair stand, and range of motion (ROM) by the back-scratch test.
Results
Higher ICH score was associated with lower PWV (β = -0.122, p = 0.002), lower hs-CRP (β = -0.234, p = 0.056), higher CRF [6MWT (β = 0.263, p = 0.041); Siconolfi step test (β = 0.330, p < 0.001)], higher ROM (β = 0.278, p = 0.013) and higher relative handgrip strength (β = 0.248, p = 0.024). Women with ICH status presented lower PWV (mean difference 0.40 m/s, 95% CI 0.17 to 0.63, p = 0.001), and higher CRF [assessed by 6MWT (mean difference 43.9 m, 95% CI 5.0 to 82.7, p = 0.028)], than women with non-ICH status. Sensitivity analyses using ICH score ranging 0-14 and considering ICH status with ≥5 metrics revealed consistent results.
Conclusion
ICH is associated with lower arterial stiffness, lower inflammation, and higher fitness in women with SLE. Although these results extend current knowledge about the potential role of ICH for primordial prevention of CVD in SLE, they are yet to be confirmed in future prospective research .

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

Int J Cardiol: 30 Apr 2021; 330:207-213
Hernández-Martínez A, Gavilán-Carrera B, Vargas-Hitos JA, Morillas-de-Laguno P, ... Sabio JM, Soriano-Maldonado A
Int J Cardiol: 30 Apr 2021; 330:207-213 | PMID: 33621624
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Impact:
Abstract

Risk of stent failure in patients with diabetes treated with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors: A nationwide observational study.

Santos-Pardo I, Lagerqvist B, Ritsinger V, Witt N, Norhammar A, Nyström T
Background
Incretins are a group of glucose-lowering drugs with favourable cardiovascular (CV) effects against neoatherosclerosis. Incretins\' potential effect in stent failure is unknown. The aim of this study is to determine if incretin treatment decreases the risk of stent-thrombosis (ST), and/or in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) with implanted drug-eluting stents (DES).
Methods
Observational study including all diabetes patients who underwent PCI with DES in Sweden from 2007 to 2017. By merging 5 national registers, the information on patient characteristics, outcomes and drug dispenses was retrieved. Cox regression analysis with estimated hazard ratios (HRs) adjusted for confounders with 95% confidence intervals (CIs) was used to analyse for the occurrence of ST/ISR, and major adverse cardiovascular events (MACE). A subgroup analysis for the type of incretin treatment was performed.
Results
In total 18,505 diabetes patients (30% women) underwent PCI, and 32,463 DES were implanted. Of those, 10% (3449 DES in 1943 patients) were treated with incretins. Median follow-up time was 995 days (Control Group) vs. 771 days (Incretin Group). No significant difference in the risk of ST/ISR was found neither for the main study group (HR:0.98 95% CI:0.80-1.19) nor for the subgroups. No reduction of the risk of MACE (HR:0.96 95% CI:0.88-1.06) was observed. There was a 26% lower risk for CV death in favour of incretin treated patients (HR:0.74 95% CI:0.57-0.95).
Conclusion
In diabetes patients who underwent PCI incretin treatment was not associated with lower risk of stent failure, but with lower risk of CV death.

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

Int J Cardiol: 30 Apr 2021; 330:23-29
Santos-Pardo I, Lagerqvist B, Ritsinger V, Witt N, Norhammar A, Nyström T
Int J Cardiol: 30 Apr 2021; 330:23-29 | PMID: 33621623
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Impact:
Abstract

Differentiation of athlete\'s heart and hypertrophic cardiomyopathy by the fractal dimension of left ventricular trabeculae.

Vilades D, Garcia-Moll X, Gomez-Llorente M, Pujadas S, ... Carreras F, Cinca J
Background
Differentiation between exercise induced adaptive myocardial hypertrophy (athlete\'s heart) and hypertrophic cardiomyopathy (HCM) is currently based on echocardiographic and cardiac magnetic resonance (CMR) criteria, but these may be insufficient in patients with subtle phenotype expression. This study aimed to assess whether left ventricular (LV) fractal pattern could permit to differentiate athlete\'s heart from HCM.
Methods
We recruited retrospectively 61 elite marathon runners, 67 patients with HCM, and 33 healthy subjects. A CMR study was performed in all subjects and the LV trabeculae fractal dimension (FD) was measured in end-diastolic frames of each short-axis cine sequence. For group comparison, the ratio of maximal myocardial wall thickness (mMWT)/indexed LV end-diastolic volume (LVED) was determined.
Results
As compared with athletes, patients with HCM had significantly (p < 0.001) greater FD in the LV basal (1.30 ± 0.07 vs. 1.23 ± 0.05) and apical (1.38 ± 0.06 vs. 1.30 ± 0.07) regions and in the whole heart (1.34 ± 0.05 vs. 1.27 ± 0.05). FD increased with age, left atrial area and indexed left ventricular mass (p < 0.05 for all) and correlated negatively with LV and RV end-diastolic volumes (p < 0.05 each). The addition of whole heart FD to the ratio of maximal myocardial wall thickness/indexed LVEDV lead to an improvement in the ability to discriminate HCM with a net reclassification index (NRI) of 71%.
Conclusions
The FD regional distribution of the LV trabeculae differentiates patients with athlete\'s heart from patients with HCM. The addition of whole heart FD to the mMWT/indexed LVEDV ratio improves the predictive capacity of the model to differentiate both entities.

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

Int J Cardiol: 30 Apr 2021; 330:232-237
Vilades D, Garcia-Moll X, Gomez-Llorente M, Pujadas S, ... Carreras F, Cinca J
Int J Cardiol: 30 Apr 2021; 330:232-237 | PMID: 33621621
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Impact:
Abstract

Surgical and percutaneous management of aboriginal Australians with rheumatic heart disease: Timeliness and concordance between practice and guidelines.

Roberts-Thomson RL, Baumann A, Reade J, Culgan L, ... Psaltis PJ, Brown A
Background
Rheumatic heart disease (RHD) affects over 40 million people globally who are predominantly young and from impoverished communities. The barriers to valvular intervention are complex and contribute to the high morbidity and mortality associated with RHD. The rates of guideline indicated intervention in patients with significant RHD have not yet been reported.
Methods
From 2007 to 2017, we used the Australian Northern Territory Cardiac Database to identify patients with RHD who fulfilled at least one ESC/EACTS guideline indication for mitral valve intervention. Baseline clinical status, comorbidities, echocardiographic parameters, indication for intervention, referral and any interventions were recorded.
Results
154 patients (mean age 38.5 ± 14.6, 66.1% female) were identified as having a class I or IIa indication for invasive management. Symptoms, atrial fibrillation and pulmonary hypertension were the most common indications for surgery (74.5%, 48.1%, 40.9%). From the onset of a guideline indication the actuarial rates of accepted referral and intervention within two-years were 66.0% ± 4.0% and 53.1% ± 4.4% respectively. Of those who were referred and accepted for intervention, 86% received it within 2 years. The rates of accepted referral for patients with class I indications were 72.5% ± 4.2% while class IIa indications were 42.5% ± 9.0% (p < 0.001).
Conclusions
Approximately half of Aboriginal patients with significant rheumatic mitral valve disease who met ESC/EACTS guideline indications for intervention received surgery or valvuloplasty within two-years. A significant difference in referral rates was found between Class I and Class IIa indications for valvular intervention.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 17 Apr 2021; epub ahead of print
Roberts-Thomson RL, Baumann A, Reade J, Culgan L, ... Psaltis PJ, Brown A
Int J Cardiol: 17 Apr 2021; epub ahead of print | PMID: 33882270
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Impact:
Abstract

Association between coronary artery calcium score and stent expansion in percutaneous coronary intervention.

Komaki S, Ishii M, Ikebe S, Kaichi R, ... Kurogi K, Yamamoto N
Background
Measurement of the coronary artery calcification score using multidetector computed tomography (MDCT) is a useful noninvasive test for the diagnosis of coronary artery disease. However, whether pre-intervention assessment of the target vessel coronary artery calcification (TV-CAC) score is associated with stent expansion failure and future target lesion revascularization (TLR), remains unknown. This study aimed to determine the association between the TV-CAC score measured by MDCT and stent expansion rate in patients who underwent IVUS-guided PCI for stable angina.
Methods
We conducted a retrospective observational study including 135 consecutive patients (186 target lesions) who underwent MDCT and were scheduled for the first PCI. The patients were divided into 2 groups based on the median value of the TV-CAC score. The primary outcome was the stent expansion rate measured by IVUS after stent implantation. The secondary outcome was TLR within 1 year.
Results
Stent expansion rate was associated with the TV-CAC score (p < 0.001). According to the ROC curve analysis, the TV-CAC score had the largest area under the curve (AUC) for the stent expansion area of 0.90 (AUC = 0.893, p < 0.001). The TV-CAC score was a positive predictor for stent expansion rate of <90% (odds ratio: 7.54, p < 0.001). Mediation analysis showed that stent under-expansion was a mediator of the association between high TV-CAC and TLR.
Conclusions
Our study demonstrates that pre-intervention assessment of TV-CAC using MDCT is a predictor of stent expansion. The TV-CAC score might predict the complexity and help in the PCI operative strategy.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 16 Apr 2021; epub ahead of print
Komaki S, Ishii M, Ikebe S, Kaichi R, ... Kurogi K, Yamamoto N
Int J Cardiol: 16 Apr 2021; epub ahead of print | PMID: 33878373
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Impact:
Abstract

Identification of a novel presumed cardiac sarcoidosis category for patients at high risk of disease.

Rosenbaum AN, Kolluri N, Elwazir MY, Kapa S, ... Schmidt TJ, Cooper LT
Background
Histologic evidence is required for a definitive diagnosis of cardiac sarcoidosis (CS) by published guidelines; however, the sporadic nature of the disease may produce false negative biopsy results, causing CS to be underdiagnosed. We sought to establish a clinical category of CS absent histologic findings.
Methods
Patients evaluated for CS were stratified into 3 groups: probable CS and definite CS based on Heart Rhythm Society (HRS) criteria and presumed CS, ie, patients without any histologic evidence of sarcoidosis, but with unexplained high-grade atrioventricular block or ventricular arrhythmia and findings suggestive of CS on either cardiac magnetic resonance imaging or positron emission tomography. The primary end point was hospitalization-free and overall survival at 10 years.
Results
A total of 383 patients were included in the study: 59, definite CS; 223, probable CS; and 101, presumed CS (62, isolated CS and 39, systemic CS). Compared with patients meeting HRS criteria for CS, patients with presumed CS had lower odds of New York Heart Association class III or IV symptoms (odds ratio [OR], 0.44 [95% CI, 0.23-0.83]; P = .01) but greater odds of previous ventricular tachycardia (OR, 2.4 [95% CI, 1.4-4.0]; P = .001) or history of resuscitated sudden cardiac arrest (OR, 2.9 [95% CI, 1.0-8.6]; P = .05). Hospitalization-free and overall survival were similar among groups (P = .51 and P = .71, respectively).
Conclusions
Clinical categorization of patients with presumed CS identified a high-risk cohort comparable to patients with histologic evidence of disease, although caution should be exercised in reaching this diagnosis without paying due diligence to the differential diagnosis.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 16 Apr 2021; epub ahead of print
Rosenbaum AN, Kolluri N, Elwazir MY, Kapa S, ... Schmidt TJ, Cooper LT
Int J Cardiol: 16 Apr 2021; epub ahead of print | PMID: 33878372
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Impact:
Abstract

A sex paradox in clinical outcomes following complex percutaneous coronary intervention.

Nicolas J, Claessen BE, Cao D, Chiarito M, ... Dangas GD, Mehran R
Background
Although the number of complex percutaneous coronary intervention (CPCI) procedures is increasing, data regarding sex-related outcomes following CPCI are scarce.
Methods
We retrospectively analyzed data of patients enrolled in a single-center registry between 2009 and 2017. Patients were divided into two groups (CPCI and non-CPCI) stratified by sex. CPCI was defined as any PCI procedure with ≥1 of the following characteristics: ≥3 target vessels/lesions, ≥3 stents implanted, bifurcation with ≥2 stents, stent length > 60 mm, or chronic total occlusion. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and target vessel revascularization, at oneon-year follow-up.
Results
Among 20,419 patients, 5004 (24.5%) underwent CPCI of whom 25.6% (n = 1281) women and 74.4% (n = 3723) men. Women presented with more comorbidities yet less complex coronary anatomy than men (syntax score: 19.5 ± 10.3 vs. 20.6 ± 10.7, p = 0.009). Moreover, women were more likely to fulfill a single rather than multiple CPCI criteria. At one year, a higher rate of MACE occurred in women (14.0% vs. 11.6%, p = 0.02). After multivariable adjustment for confounders, the risk of MACE at one year was similar among both sexes (HR:1.04, 95% CI [0.85-1.26], p = 0.71), without significant interaction between the complexity of the procedure and sex (p-interaction = 0.96). Nonetheless, the risk of MI was significantly higher in women than men undergoing CPCI (HR:1.63, 95% CI [1.12-2.38], p = 0.01).
Conclusions
Despite presenting with less challenging lesions than men, women had a higher rate of MI at one year following CPCI, even after adjusting for potential confounders.

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

Int J Cardiol: 14 Apr 2021; 329:67-73
Nicolas J, Claessen BE, Cao D, Chiarito M, ... Dangas GD, Mehran R
Int J Cardiol: 14 Apr 2021; 329:67-73 | PMID: 33278415
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Impact:
Abstract

Cost of inpatient heart failure care and 30-day readmissions in the United States.

Kwok CS, Abramov D, Parwani P, Ghosh RK, ... Van Spall HGC, Mamas MA
Background
Heart failure hospitalizations are a major financial cost to healthcare systems. This study aimed to evaluate the costs associated with inpatient hospitalization.
Methods
Patients with a primary diagnosis of heart failure during a hospital admission between 2010 and 2014 in the U.S. Nationwide Readmission Database were included. The primary outcome was total cost defined by direct cost of index admission and first readmission within 30-days.
Results
A total of 2,645,336 patients with primary heart failure were included in the analysis. The mean ± SD total cost overall was $13,807 ± 24,145; with mean total costs of $15,618 ± 25,264 for patients with 30-day readmission and $11,845 ± 22,710 for patients without a readmission. The comorbidities strongly associated with increased cost were pulmonary circulatory disorder (OR 26.24 95% CI 20.06-34.33), valvular heart disease (OR 25.42 95% CI 20.65-31.28) and bleeding (OR 5.96 95% CI 5.47-6.50). Among hospitalized patients, 12.6% underwent an invasive diagnostic procedure or treatment. The mean cost for patients without invasive care was $10,995. This increased by $129,547, $119,769, $251,110 and $293,575 for receipt of circulatory support, intra-aortic balloon pump, LV assist device and heart transplant. The greatest mean additional cost annually was associated with receipt of coronary angiogram ($26,282 per person for a total of ($728.5 million) and mechanical ventilation ($54,529 per person for a total of $501.7 million).
Conclusion
In conclusion, the costs associated with inpatient heart failure care are significant, and the major contributors to inpatient costs are comorbidities, invasive procedures and readmissions.

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

Int J Cardiol: 14 Apr 2021; 329:115-122
Kwok CS, Abramov D, Parwani P, Ghosh RK, ... Van Spall HGC, Mamas MA
Int J Cardiol: 14 Apr 2021; 329:115-122 | PMID: 33321128
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Impact:
Abstract

Predictive value of the Kuijer score for bleeding and other adverse in-hospital events in patients with venous thromboembolism.

Keller K, Münzel T, Hobohm L, Ostad MA
Background
Venous thromboembolism (VTE) constitute a major global burden of disease. Current international guidelines recommend treatment with anticoagulant therapy after VTE for a duration of at least 3 months. Since anticoagulation also imposes an increased risk for bleeding events, the individual risk has to be evaluated to determine adequate treatment plans.
Methods
The nationwide German inpatient sample of the years 2005-2017 was used for this analysis. Hospitalized VTE patients were stratified according to Kuijer risk class and the performance of the Kuijer score was evaluated to predict adverse in-hospital events.
Results
Overall, 1,204,895 VTE patients were treated between 2005 and 2017 in Germany and were included in the present study (839,143 patients had deep venous thrombosis and/or thrombophlebitis and 669,881 patients pulmonary embolism). According to Kuijer risk class stratification, in total, 176,723 (14.7%) of the hospitalized VTE patients were classified as low risk, 914,964 (75.9%) as intermediate risk and 113,208 (9.4%) as high risk. A higher Kuijer risk class was predictive for in-hospital death (odds ratio [OR] 1.99 [95% confidence interval (CI) 1.96-2.02], P < 0.001), major adverse cardiovascular and cerebrovascular events (MACCE, OR 1.90 [95%CI 1.87-1.93], P < 0.001), intracerebral bleeding (OR 1.28 [95%CI 1.14-1.44], P < 0.001), gastrointestinal bleeding (OR 1.56 [95%CI 1.48-1.64], P < 0.001) as well as necessity of transfusion of blood constituents (OR 2.94 [95%CI 2.88-3.00], P < 0.001) independently of important comorbidities.
Conclusions
The Kuijer score is an important risk stratification tool to predict individual risk regarding in-hospital outcomes comprising major bleeding events such as intracerebral bleeding and necessity of transfusion of blood constituents, but also in-hospital mortality and MACCE in VTE patients.

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

Int J Cardiol: 14 Apr 2021; 329:179-184
Keller K, Münzel T, Hobohm L, Ostad MA
Int J Cardiol: 14 Apr 2021; 329:179-184 | PMID: 33301828
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Impact:
Abstract

A genome-wide association study for highly sensitive cardiac troponin T levels identified a novel genetic variation near a RBAK-ZNF890P locus in the Japanese general population.

Nasu T, Satoh M, Hachiya T, Sutoh Y, ... Shimizu A, Sasaki M
Background
Cardiovascular disease (CVD) is a major cause of mortality worldwide. High-sensitivity cardiac troponin T (hs-cTnT) is released into the bloodstream due to cardiomyocyte damage and is associated with a high CVD risk. This study aimed to investigate hs-cTnT-related genetic variation and to examine whether this is an associated risk factor for CVD in the Japanese general population.
Methods
This was a genome-wide association study (GWAS) based on a cohort from the 2013 Tohoku Medical Megabank Project community study. The GWAS was performed using a HumanOmniExpressExome BeadChip array with 914,035 autosomal single-nucleotide polymorphisms. The Framingham Risk Score and the Suita score were used to evaluate the future risk of CVD.
Results
The GWAS identified 10 loci reaching suggestive significance in the discovery cohort. A replication analysis confirmed that one of the 10 loci, rs7798496, is associated with elevated hs-cTnT levels. The combined P value in the discovery and replication cohorts for the association between the rs7798496 and hs-cTnT levels was 3.4 × 10-8, which indicates that the novel variant reached genome-wide significance. The rs7798496 loci was located at an intergenic region between the retinoblastoma gene product (RB)-associated Krüppell-associated box (KRAB) zinc finger, zinc finger protein 890, and pseudogene (ZNF890P). Logistic regression analysis revealed that the presence of the rs7798496 T allele was strongly associated with a high risk for CVD.
Conclusions
This study provides insights into a link between a novel genetic variant, T allele of rs7798269, and elevated hs-cTnT levels as a future risk for CVD in the general Japanese population.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Apr 2021; 329:186-191
Nasu T, Satoh M, Hachiya T, Sutoh Y, ... Shimizu A, Sasaki M
Int J Cardiol: 14 Apr 2021; 329:186-191 | PMID: 33321125
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Impact:
Abstract

Longitudinal assessment of right atrial conduit fraction provides additional insight to predict adverse events in pediatric pulmonary hypertension.

Frank BS, Schäfer M, Thomas TM, Ivy DD, Jone PN
Background
Recent studies show adverse right atrial (RA) emptying pattern is prognostic for clinical worsening events in pediatric pulmonary arterial hypertension (PAH). No study has reported changes in RA emptying over time or evaluated whether serial measurements offer further prognostic information.
Methods
Prospective study of 32 children with idiopathic or heritable PAH undergoing echocardiogram at baseline and 1-year. RA conduit fraction percent (RA cF%) was measured as percentage of total diastolic RA area change prior to the electrical p wave. Clinical worsening was analyzed with a predefined composite adverse event outcome.
Results
Longitudinal subjects (median age 13.3 yr) had RA cF% 61% (IQR 32-68%) at baseline and 60% (IQR 35-73%) at 1-year (NS). 11 subjects had a qualifying event during median 21-month follow-up. Subjects with an event had 1-year RA cF% = 33% (IQR 20-40%) compared to 72% (IQR 63-75%) for those with no event (p < 0.001). Event rates were lowest for subjects with both echocardiograms showing RA cF% > 60% (0%), highest for subjects with neither (80%), and intermediate for those with one (38%, p = 0.003).
Conclusions
Changes in RA cF% inform risk of adverse events in pediatric PAH. This finding supports the role of RA cF% as both a prognostic biomarker and potential treatment target.

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

Int J Cardiol: 14 Apr 2021; 329:242-245
Frank BS, Schäfer M, Thomas TM, Ivy DD, Jone PN
Int J Cardiol: 14 Apr 2021; 329:242-245 | PMID: 33400972
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Impact:
Abstract

The shape of the left lateral ridge as a predictor of long-term outcome of catheter ablation for atrial fibrillation based on clinical and experimental data.

Kim S, Kim YR, Nam GB, Choi KJ, Kim YH
Background
The left lateral ridge (LLR) is an important structure for ablation of atrial fibrillation (AF). This study assessed how the LLR shape is associated with the long-term outcomes of AF ablation and investigated the relationship with radiofrequency (RF) lesion formation.
Methods and results
Clinical study - we assessed multi-detector computed tomography (MDCT) images in 247 patients who underwent AF ablation. Patients were classified into two groups according to the shape of the LLR: Narrow LLR group (n = 116; 47%) and Wide LLR group (n = 131; 53%). After a follow-up period 475 ± 245 days, the AF-free rate was significantly higher in the wide LLR than Narrow LLR group (83.2% vs. 62.9%, p = 0.0004). A multivariate analysis showed that the shape of the LLR was an independent predictor of AF recurrence after ablation (hazard ratio 2.58; 95% confidential interval = 1.48-4.51, p = 0.001). Experimental study - Two types of the ridge models were made with porcine atrial tissues: \"Narrow ridge(4.2 ± 0.9 mm)\" and \"Wide ridge(9.7 ± 1.8 mm)\" RF ablation was performed on each ridge model using a contact force (CF)-sensing catheter. The mean CF and the RF lesion volume of the narrow ridge were significantly less than those of the wide ridge model (5.42 ± 3.13 g vs. 10.37 ± 3.98 g, p = 0.001; 19.8 ± 9.9 mm3 vs. 44.2 ± 13.6 mm3, p < 0.001, respectively).
Conclusions
AF recurrence after ablation was more frequent in patients with a narrow LLR. LLR shape as assessed using MDCT is associated with long-term outcomes after AF ablation. CF and lesion formation data using the porcine atrial tissue model support our clinical results.

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

Int J Cardiol: 14 Apr 2021; 329:91-98
Kim S, Kim YR, Nam GB, Choi KJ, Kim YH
Int J Cardiol: 14 Apr 2021; 329:91-98 | PMID: 33370558
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Impact:
Abstract

The prognostic value of immediate post-TAVI hemodynamic evaluation is superior to aortography and transoesophageal echocardiography in predicting patient survival.

Dekany G, Fontos G, Satish S, Szabo G, ... Ferenci T, Andreka P
Background
Although post-TAVI PAR is commonly seen, its exact evaluation, grading and the true impact on patients\' survival are still debated. This single center study aimed to evaluate the effect of post transcatheter aortic valve implantation (TAVI) paravalvular aortic regurgitation (PAR) on patients\' survival. The outcome was evaluated by the three most commonly used techniques just after TAVI in the interventional arena.
Methods
201 high risk patients with severe symptomatic aortic stenosis underwent TAVI with the self-expandable system. The severity of post-TAVI PAR was prospectively evaluated by aortography and transesophageal echocardiography (TEE) using a four-class scheme and hemodynamic evaluation by calculation of the regurgitation index (RI). Median follow up time was 763 days.
Results
Post-TAVI PAR results of the three different modalities were concordant with each other (all p < 0.001). Patients with grade 0-I PAR by aortography had better long term outcomes compared to those who had grade II-III PAR (unadjusted HR 1.77 [95% CI, 1.04-3.01], p = 0.03). Although in multivariate analysis neither aortography nor TEE were shown to be significant predictors of survival, hemodynamic assessment using the exact RI result was a significant predictor of survival and its effect was found to be linear (adjusted HR 0.72 [95% CI, 0.52-0.98] for 10% point increase in RI, p = 0.03595).
Conclusions
Among the three modalities that are frequently used to evaluate the outcome, post-TAVI RI showed the highest added predictive value for survival.

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

Int J Cardiol: 14 Apr 2021; 329:153-161
Dekany G, Fontos G, Satish S, Szabo G, ... Ferenci T, Andreka P
Int J Cardiol: 14 Apr 2021; 329:153-161 | PMID: 33359335
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Impact:
Abstract

Impact of contrast medium osmolality on the risk of acute kidney injury after transcatheter aortic valve implantation: insights from the Magna Graecia TAVI registry.

Iacovelli F, Pignatelli A, Cafaro A, Stabile E, ... Tesorio T, Contegiacomo G
Background
Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is frequent and associated with adverse outcomes and mortality; to date, in such setting of patients there is no consistent evidence that either low-osmolar contrast media (LOCM) or iso-osmolar contrast medium (IOCM) are superior to the other in terms of renal safety.
Methods
697 consecutive patients not in hemodialysis treatment who underwent TAVI (327 males, mean age 81.01 ± 5.75 years, mean european system for cardiac operative risk evaluation II 6.17 ± 0.23%) were enrolled. According to osmolality of the different iodinated CM, the population was divided in 2 groups: IOCM (n = 370) and LOCM group (n = 327). Preoperatively, 40.54% of patients in IOCM vs 39.14% in LOCM group (p = 0.765) suffered from chronic kidney disease (CKD).
Results
The incidence of AKI was significantly lower with IOCM (9.73%) than with LOCM (15.90%; p = 0.02), and such significant difference (p < 0.001) in postprocedural change of renal function parameters persisted at discharge too. The incidence of AKI was also significantly lower with IOCM in younger patients, without diabetes, anemia, coronary artery disease history, CKD, chronic or persistent atrial fibrillation, left ventricular ejection fraction ≤35%, and in patients with low operative mortality risk scores, receiving lower amounts of dye (p < 0.05 for all). Importantly, multivariate analysis identified LOCM administration as an independent risk factor for both AKI (p = 0.006) and 1-year mortality (p = 0.001).
Conclusions
The use of IOCM have a favorable impact on renal function with respect to LOCM, but it should be considered especially for TAVI patients at lower AKI risk.

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

Int J Cardiol: 14 Apr 2021; 329:56-62
Iacovelli F, Pignatelli A, Cafaro A, Stabile E, ... Tesorio T, Contegiacomo G
Int J Cardiol: 14 Apr 2021; 329:56-62 | PMID: 33359334
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Impact:
Abstract

Evolution of acute myocarditis in a pediatric population: An MRI based study.

Martins DS, Ait-Ali L, Khraiche D, Festa P, ... Aquaro GD, Raimondi F
Background
Cardiac Magnetic Resonance (CMR) data regarding myocarditis presentation and disease course is still lacking in pediatric patients. We evaluate baseline CMR and evolution of functional and tissue abnormalities in children with acute myocarditis.
Methods
CMR was performed in 125 patients with clinical diagnosis of acute myocarditis. Clinical follow-up was performed for a median of 498 (214-923) days.
Results
LVEF was depressed (<55%) in 56 cases (45%) upon baseline CMR. LGE was found in 93 patients (77%) of cases. LGE was exclusively subepicardial in 29 patients (23%), while other LGE patterns (midwall/mixed) were present in 64 (51%). CMR was repeated in 92 (74%) patients. 67% presented recover of function at a median of 170 (70-746) days after onset of symptoms. Midwall/mixed LGE pattern had a statistically significant correlation with absent recover of function (OR 0.20 p 0.036). Thirteen patients (16%) had recovery from LV dysfunction but with persistence of LGE. Sub-epicardial pattern of LGE (OR 3.33, 95% CI 1.08-10.2, p = 0.036) and the presence of fever at admission (OR 4.67, 95% CI 1.16-18.7, p = 0.03) were associated with a significantly higher likelihood of complete normalization while midwall/mixed LGE pattern was associated with non-recovery.
Conclusions
In pediatric myocarditis, midwall/mixed LGE pattern is associated with absent recover of function. Patients with recover of function may still have persistence of LGE, while a complete recovery from functional and tissue abnormalities is found only in a third of patients. Midwall/mixed pattern of LGE at first MRI was associated to worse outcome.

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

Int J Cardiol: 14 Apr 2021; 329:226-233
Martins DS, Ait-Ali L, Khraiche D, Festa P, ... Aquaro GD, Raimondi F
Int J Cardiol: 14 Apr 2021; 329:226-233 | PMID: 33359333
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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: 14 Apr 2021; 329:192-197
Jabłońska A, Zagrapan B, Neumayer C, Eilenberg W, ... Nanobachvili J, Huk I
Int J Cardiol: 14 Apr 2021; 329:192-197 | PMID: 33359288
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Impact:
Abstract

Clinical characteristics of patients with takotsubo syndrome recurrence: An observational study with long-term follow-up.

Arcari L, Cacciotti L, Limite LR, Russo D, ... Autore C, Musumeci MB
Background
Research investigating takotsubo syndrome (TTS) recurrence yielded conflicting results. Aim of the present study is to describe clinical characteristics of patients with TTS recurrence in a cohort with available long-term follow-up.
Methods
The study population included 234 TTS patients enrolled in a prospective multicenter registry, median follow-up of 1328 (407, 2526) days. To investigate factors associated with TTS recurrence, we analyzed patients with recurrence (Group A) in comparison with a subgroup of TTS patients within the whole population (group B) who had similar age, sex and median follow-up length (Group A 2280 days vs Group B 2361 days).
Results
We observed 9 TTS recurrences affecting 8 patients, all women, with a rate of 0.9% patients/year. Median time to first recurrence was 1593 days (interquartile range: 950, 2516). We detected no significant differences between patients with and without recurrences regarding cardiovascular risk factors, symptoms, ECG and echocardiographic findings at presentation, discharge therapy. Physical trigger and chronic obstructive pulmonary disease (COPD) were more prevalent in patients who experienced a recurrence (75% vs 27% and 50% vs 14% with p = 0.01 and p = 0.022 respectively). Univariable Cox regression analysis identified physical trigger and history of COPD to be both associated with TTS recurrence [hazard ratio (HR) 11.4, 95% confidence interval (CI) 2.29-56.8, p = 0.003 and HR 4.94, 95% CI 1.16-20.99 p = 0.031 respectively].
Conclusion
TTS recurrence is relatively uncommon. Association with physical trigger and COPD would suggest a closer follow-up in this subgroup of patients.

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

Int J Cardiol: 14 Apr 2021; 329:23-27
Arcari L, Cacciotti L, Limite LR, Russo D, ... Autore C, Musumeci MB
Int J Cardiol: 14 Apr 2021; 329:23-27 | PMID: 33359286
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