Journal: Int J Cardiol

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Abstract

Assessing the safety and efficacy of TAVR compared to SAVR in low-to-intermediate surgical risk patients with aortic valve stenosis: An overview of reviews.

Mc Morrow R, Kriza C, Urbán P, Amenta V, ... Chassaigne H, Griesinger CB
Background
Transcatheter aortic valve replacement (TAVR) was initially introduced to treat patients with aortic valve stenosis (AS) at high-risk for surgical aortic valve replacement (SAVR). Today, there is ample evidence supporting TAVR in high-risk groups. However, in recent years TAVR has been extended to low-to intermediate risk groups and relevant clinical evidence is still emerging, leaving some uncertainties.
Methods
To obtain information on TAVR versus SAVR in low-to intermediate risk groups, we conducted an overview of systematic reviews following PRISMA guidelines and based on a systematic search of EMBASE, MEDLINE, Cochrane and CRD databases. We focused on systematic reviews assessing mortality and VARC 2 as clinical outcomes.
Results
The majority of the 11 systematic reviews included in our study reported no differences in mortality between TAVR and SAVR at short and long-term follow-up times. Two reviews that included the most recent RCTs on low-risk patients reported a decreased mortality risk with TAVR at one-year follow-up. Regarding the secondary endpoints of stroke and MI, the majority of studies presented similar results for TAVR and SAVR. Acute Kidney Injury, Bleeding Complications, Atrial Fibrillation were less frequent with TAVR, with lower risk of Permanent Pacemaker Implantation and Aortic Regurgitation with SAVR.
Conclusions
Our overview indicated that TAVR is a promising intervention for low-to-intermediate surgical risk patients; however additional evidence from longer term follow-up is needed to confirm these findings. This overview highlights inconsistencies about reporting and presentation of data, most notably limited clarity on effects of risk of bias on trial results.

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

Int J Cardiol: 31 Aug 2020; 314:43-53
Mc Morrow R, Kriza C, Urbán P, Amenta V, ... Chassaigne H, Griesinger CB
Int J Cardiol: 31 Aug 2020; 314:43-53 | PMID: 32434749
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Abstract

Prediction of new-onset atrial fibrillation for general population in Asia: A comparison of C2HEST and HATCH scores.

Hu WS, Lin CL
Purpose
To explore the use of the C2HEST and HATCH scores to predict the incidence of atrial fibrillation (AF) in Asians.
Method
The predictive capability of AF of C2HEST and HATCH scores was estimated by area under the receiver operating characteristic curve (AUROC). DeLong test was used to compared the difference of AUROC between the 2 scores.
Result
A total of 692,691 subjects were investigated. The risk of AF increased with increasing C2HEST and HATCH scores (p for trend<0.001). The AUROC for C2HEST and HATCHs in predicting AF occurrence was 0.7895 and 0.7711, respectively. C2HEST score had a significant better capability for AF stratification than HATCH score (DeLong test <0.001).
Conclusion
Higher C2HEST and HATCH scores were more strongly associated with the incidence of AF. The C2HEST score appeared to be more predictive of AF than the HATCH score.

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

Int J Cardiol: 14 Aug 2020; 313:60-63
Hu WS, Lin CL
Int J Cardiol: 14 Aug 2020; 313:60-63 | PMID: 32336574
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Abstract

Long-term follow-up and predictors of target lesion failure after implantation of everolimus-eluting bioresorbable scaffolds in real-world practice.

Wiebe J, Baquet M, Dörr O, Hoppmann P, ... Kastrati A, Nef H
Background
Bioresorbable scaffolds (BRS) have been shown to be inferior to drug-eluting stents in randomized trials. Nevertheless, patients treated during daily routine differ from those treated within randomized trials and thus need further long-term evaluation. The present investigation aims to address this lack.
Methods
Consecutive patients with coronary artery disease treated with implantation of everolimus-eluting BRS at 5 centers in Germany were included. Clinical follow-up was assessed up to 3 years. Analysis of clinical outcomes was performed by pooling of the individual patient data sets of each center. The major clinical endpoints of interest was target lesion failure (TLF) a composite of cardiac death, target vessel myocardial infarction and target lesion revascularization. Furthermore occurrence of definite scaffold thrombosis was evaluated. A multivariable Cox regression analysis was applied to identify independent predictors of TLF.
Results
A total of 1614 patients treated with BRS were analyzed (mean age 64.0 ± 10.9 years, 75.8% male, 28.3% diabetics). A total 1817 lesions were treated with BRS and 56.0% were considered to be complex. At 3 years, the rate of TLF was 17.1% and definite scaffold thrombosis was noted in 2.6%. Independent predictors of TLF were a higher age, diabetes, bifurcation, complex lesions and the use of small BRS.
Conclusions
In this large-scale analysis of patients undergoing BRS implantation in daily routine, event rates were high, but in line with randomized studies. Predictors of TLF were identified which may optimize patient and lesion selection for BRS.

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

Int J Cardiol: 31 Jul 2020; 312:42-47
Wiebe J, Baquet M, Dörr O, Hoppmann P, ... Kastrati A, Nef H
Int J Cardiol: 31 Jul 2020; 312:42-47 | PMID: 32151443
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Abstract

Heart transplantation at a single tertiary adult congenital heart disease centre: Too little, too late?

Merás P, Riesgo-Gil F, Rybicka J, Barradas-Pires A, ... Simon A, Gatzoulis MA
Background
Heart failure (HF) is the leading cause of death in adults with congenital heart disease (ACHD). Heart transplantation can be an effective therapy for them, albeit unfavourable anatomy, end-organ damage, pulmonary vascular disease, HLA sensitization and lack of robust selection criteria currently limit its application.
Methods
Consecutive CHD patients considered for heart or combined heart and lung transplantation at our tertiary ACHD centre between 2000 and 2018 constitute our study population. Baseline characteristics and outcome, including transplantation and death, were obtained for all patients from designated databases, medical records and the UK Office for National Statistics.
Results
From a total of more than 9000 active ACHD patients under follow-up, 166 (median age 40.4 years) fulfilled inclusion criteria, with a broad spectrum of underlying diagnosis: univentricular heart 22.3%, systemic right ventricle 22.3%, systemic-to-pulmonary shunts and Eisenmenger syndrome 16.3%, left sided valvular lesions 14.5%, tetralogy of Fallot 12.7%, CHD associated with cardiomyopathy 4.8% and other 7.2%. There was a high overall mortality with 39.2% of patients dying over a median follow-up of 2.7 years. A minority of patients (22.9%) were eventually listed and only 13.3% from the 166 patients were actually transplanted. Survival at 1 year after transplantation was 81.8% and remained high long-term (65.5% at 15 years). We describe herewith in detail characteristics and outcome of our cohort and present the transplantation pathway followed.
Conclusion
Of the small number of patients with ACHD considered for heart transplantation at a large tertiary centre, there was high overall mortality, with only a fraction of patients being actually transplanted. Patients who received transplantation, however, had a good outcome. Better patient selection and timing are clearly warranted so that more ACHD patients are considered and potentially benefit from this effective form of therapy.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 12 Aug 2020; epub ahead of print
Merás P, Riesgo-Gil F, Rybicka J, Barradas-Pires A, ... Simon A, Gatzoulis MA
Int J Cardiol: 12 Aug 2020; epub ahead of print | PMID: 32798622
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Abstract

Associations between changes in serum uric acid and the risk of myocardial infarction.

Tian X, Zuo Y, Chen S, Wang A, ... Wu S, Luo Y
Background
The role of serum uric acid (SUA) in development of myocardial infarction (MI) is controversial. The current study aimed to investigate the association between both baseline SUA and changes in SUA and the risk of MI.
Methods
The current study included 71,449 Chinese participants (mean age, 50.9 years) free of MI during the time of follow-up. Participants were divided into 4 categories according to the SUA levels between baseline and the second follow-up: stable low, elevated, reduced and stable high. Multivariate Cox proportion models were used to calculated hazard ratios (HRs) and their 95% confidence intervals (CIs) for MI.
Results
During a median follow-up of 8.96 years, 837 MI cases were identified. After adjustment for potential confounders, MI risk was only associated with stable high SUA, the HR was 1.42 (95%CI: 1.02-1.92, p = 0.03), compared with those with stable low SUA. However, there was no association between hyperuricemia at baseline and MI, the HR was 1.14 (95%CI: 0.91-1.42, p = 0.19) compared with those with normal SUA. Subgroup analyses stratified by age, sex, hypertension, diabetes and estimated glomerular filtration rate were also confirmed no significant difference (p-interaction >0.05 for all). Furthermore, mediation analyses revealed 14.14% of association was mediated by hypertension.
Conclusions
Only stable high SUA was associated with increased higher risk of MI. Changes in SUA levels in any other direction or high SUA levels at baseline were not associated with risk of MI.

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

Int J Cardiol: 31 Aug 2020; 314:25-31
Tian X, Zuo Y, Chen S, Wang A, ... Wu S, Luo Y
Int J Cardiol: 31 Aug 2020; 314:25-31 | PMID: 32333932
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Abstract

Experimental abdominal aortic aneurysm growth is inhibited by blocking the JAK2/STAT3 pathway.

Xiao J, Wei Z, Chen X, Chen W, ... Shang Y, Liu J
Background
The JAK/STAT pathway is a vital transcription signaling pathway that regulates gene expression and cellular activity. Our recently published study highlighted the role of IL-17A in abdominal aortic aneurysm (AAA) formation and rupture. IL-17A has been proven to upregulate vascular endothelial growth factor (VEGF) expression in some diseases. However, no study has demonstrated the relationships among JAK2/STAT3, IL-17A and VEGF. Therefore, we hypothesized that IL-17A may up-regulate VEGF expression via the JAK2/STAT3 signaling pathway to amplify the inflammatory response, exacerbate neovascularization, and accelerate AAA progression.
Methods
To fully verify our hypothesis, two separate studies were performed: i) a study investigating the influence of JAK2/STAT3 on AAA formation and progression. ii) a study evaluating the relationship among IL-17A, JAK2/STAT3 and VEGF. Human tissues were collected from 7 AAA patients who underwent open surgery and 7 liver transplantation donors. All human aortic tissues were examined by histological and immunohistochemical staining, and Western blotting. Furthermore, mouse aortic tissues were also examined by histological and immunohistochemical staining and Western blotting, and the mouse aortic diameters were assessed by high-resolution Vevo 2100 microimaging system.
Results
Among human aortic tissues, JAK2/STAT3, IL-17A and VEGF expression levels were higher in AAA tissues than in control tissues. Group treated with WP1066 (a selective JAK2/STAT3 pathway inhibitor), IL-17A, and VEGF groups had AAA incidences of 25%, 40%, and 65%, respectively, while the control group had an incidence of 75%. Histopathological analysis revealed that the IL-17A- and VEGF-related inflammatory responses were attenuated by WP1066. Thus, blocking the JAK2/STAT3 pathway with WP1066 attenuated experimental AAA progression. In addition, in study ii, we found that IL-17A siRNA seemed to attenuate the expression of IL-17A and VEGF in vivo study; treatment with VEGF siRNA decreased the expression of VEGF, while IL-17A expression remained high. In an in vitro study, rhIL-17A treatment increased JAK2/STAT3 and VEGF expression in macrophages in a dose-dependent manner.
Conclusion
Blocking the JAK2/STAT3 pathway with WP1066 (a JAK2/STAT3 specific inhibitor) attenuates experimental AAA progression. During AAA progression, IL-17A may influence the expression of VEGF via the JAK2/STAT3 signaling pathway. This potential mechanism may suggest a novel strategy for nonsurgical AAA treatment.

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

Int J Cardiol: 31 Jul 2020; 312:100-106
Xiao J, Wei Z, Chen X, Chen W, ... Shang Y, Liu J
Int J Cardiol: 31 Jul 2020; 312:100-106 | PMID: 32334849
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Abstract

Accuracy of contrast-enhanced computed tomography for thrombus detection prior to atrial fibrillation ablation and role of novel Left Atrial Appendage Enhancement Index in appendage flow assessment.

Guha A, Dunleavy MP, Hayes S, Afzal MR, ... Raman SV, Harfi TT
Aims
To evaluate diagnostic accuracy of different protocols of contrast enhanced computed tomography venogram (CTV) for LAA thrombus detection in patients undergoing AF ablation and study the correlation of the novel LAA enhancement index (LAA-EI) to LAA flow velocity obtained using transesophageal echocardiography (TEE).
Methods
Study comprised of patients undergoing CTV and TEE on the same day from October 2016 to December 2017. Three CTV scanning protocols (described in results), were evaluated wherein ECG gating was used only for those with sinus rhythm on day of CTV. LAA-EI was calculated as Hounsfield Unit (HU) in the LAA divided by the HU unit in the center of the LA. The diagnostic accuracy for CTV was calculated in comparison to TEE. The LAA-EI was compared to LAA emptying velocities as obtained from TEE.
Results
590 patients with 45.6% non-ECG-gated without delayed imaging, 26.9% non-ECG-gated with delayed imaging and 27.5% ECG-gated with delayed imaging, were included in the study. All three protocols had 100% negative predictive value with improvement in specificity from 61.8% to 98.1% upon adding delayed imaging. The LAA-EI correlated significantly with reduced LAA flow velocities (r = 0.45, p < .0001). The mean LAA emptying velocity in patients with LAA-EI of ≤ 0.6 was significantly lower than in those with LAA-EI of >0.6 (36.2 cm/s [95% CI: 32.6-39.7] vs, (58 cm/s [95% CI 55.3-60.8]), respectively (p < .0001).
Conclusion
CTV with delayed imaging (with or without ECG gating) is highly specific in ruling out LAA thrombus. The novel LAA-EI can detect low LAA flow velocities.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 31 Oct 2020; 318:147-152
Guha A, Dunleavy MP, Hayes S, Afzal MR, ... Raman SV, Harfi TT
Int J Cardiol: 31 Oct 2020; 318:147-152 | PMID: 32629004
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Abstract

Evaluation of the right heart using cardiovascular magnetic resonance imaging in patients with cardiac devices.

Löbe S, Paetsch I, Hilbert S, Spampinato R, ... Hindricks G, Jahnke C
Background
Patients with cardiac implantable electronic devices (CIED) necessitate comprehensive cardiovascular magnetic resonance (CMR) examinations. The aim of this study was to provide data on CMR image quality and feasibility of functional assessment of the right heart in patients with CIED depending on the device type and imaging sequence used.
Methods
120 CIED carriers (Insertable cardiac monitoring system, n = 13; implantable loop-recorder, n = 22; pacemaker, n = 30; implantable cardioverter-defibrillator (ICD), n = 43; and cardiac resynchronization therapy defibrillator (CRT-D), n = 12) underwent clinically indicated CMR imaging using a 1.5 T. CMR protocols consisted of cine imaging and myocardial tissue characterization including T1-and T2-weighted blackblood imaging and late gadolinium enhancement (LGE) imaging. Image quality was evaluated with regard to device-related imaging artifacts per right-ventricular (RV) segment.
Results
RV segmental evaluability was influenced by the device type and CMR imaging sequence: Cine steady-state-free-precision (SSFP) imaging was found to be non-diagnostic in patients with ICD/CRT-D and implantable loop recorders; a significant improvement of image quality was achieved when using cine turbo-field-echo (TFE) sequences with a further improvement on post-contrast TFE imaging. LGE scans were artifact-free in at least 91% of RV segments with best results in patients with a pacemaker or an insertable cardiac monitoring system.
Conclusions
In patients with CIED, artifact-free CMR imaging of the right ventricle was performed in the majority of patients and resulted in highly reproducible evaluability of RV functional parameters. This finding is of particular importance for the diagnosis and follow-up of right-ventricular diseases.

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

Int J Cardiol: 30 Sep 2020; 316:266-271
Löbe S, Paetsch I, Hilbert S, Spampinato R, ... Hindricks G, Jahnke C
Int J Cardiol: 30 Sep 2020; 316:266-271 | PMID: 32389768
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Abstract

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

Higuchi S, Hata N, Shibata S, Hirabuki K, ... Hasegawa H, Matsuda T
Background
Anemia has been recognized an important comorbidity in patients with acute heart failure (AHF) and is associated with adverse clinical events. However, the clinical impact of red blood cell (RBC) transfusion in such patients is unclear.
Method
This study was a retrospective single-center registry including AHF patients admitted to Kyorin University Hospital between 2008 and 2014. Anemia was defined as a hemoglobin level < 130 g/L in males or < 120 g/L in females. Those with major bleeding with a fall in hemoglobin concentration of >20 g/L were excluded. AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were evaluated.
Results
Of 501 AHF patients, 38 were excluded owing to major bleeding; finally, 463 (age, 77 ± 11 years; males, 58%) were evaluated. RBC transfusion during hospitalization was performed in 112 patients (24%). Hemoglobin level on admission was 105 ± 16 g/L (transfusion, 89 ± 17 g/L; no transfusion, 110 ± 12 g/L; p < 0.001). AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were observed in 46 (10%), 16 (3%), and 121 (27%) patients, respectively. Univariate Cox regression analysis demonstrated that RBC transfusion was not associated with AHF readmission at 3 months (hazard ratio: 0.80; 95% confidence interval: 0.39-1.66) The association did not differ at any hemoglobin concentration or left ventricular ejection fraction value. Multivariate Cox regression analysis revealed similar results. Furthermore, RBC transfusion was not correlated with in-hospital and 2-year all-cause mortality.
Conclusions
RBC transfusion was not associated with AHF readmission or all-cause mortality.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Sep 2020; epub ahead of print
Higuchi S, Hata N, Shibata S, Hirabuki K, ... Hasegawa H, Matsuda T
Int J Cardiol: 14 Sep 2020; epub ahead of print | PMID: 32946954
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Abstract

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

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

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 02 Oct 2020; epub ahead of print
Pana TA, Mohamed MO, Clark AB, Fahy E, Mamas MA, Myint PK
Int J Cardiol: 02 Oct 2020; epub ahead of print | PMID: 33022289
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Abstract

Safety and cost-effectiveness of same-day complex left atrial ablation.

He H, Datla S, Weight N, Raza S, ... Hayat S, Osman F
Background
Catheter ablation for complex left-atrial arrhythmia is increasing worldwide with many centres admitting patients overnight. Same-day procedures using conscious sedation carry significant benefits to patients/healthcare providers but data are limited. We evaluated the safety and cost-effectiveness of same-day complex left-atrial arrhythmia ablation.
Method
Multi-centre retrospective cohort study of all consecutive complex elective left-atrial ablation procedures performed between January 2011 and December 2019. Data were collected on planned same-day discharge versus overnight stay, baseline parameters, procedure details/success, ablation technology, post-operative complications, unplanned overnight admissions/outcomes at 4-months and mortality up to April 2020. A cost analysis of potential savings was also performed.
Results
A total of 967 consecutive patients underwent complex left-ablation using radiofrequency (point-by-point ablation aided by 3D-mapping or PVAC catheter ablation with fluoroscopic screening) or cryoballoon-ablation (mean age: 60.9 ± 11.6 years, range 23-83 yrs., 572 [59%] females). The majority of patients had isolation of pulmonary veins alone (n = 846, 87%) and most using conscious-sedation alone (n = 921, 95%). Of the total cohort, 414 (43%) had planned same-day procedure with 35 (8%) admitted overnight due to major (n = 5) or minor (n = 30) complications. Overall acute procedural success-rate was 96% (n = 932). Complications in planned overnight-stay/same-day cohorts were low. At 4-month follow-up there were 62 (6.4%) readmissions (femoral haematomas, palpitation, other reasons); there were 3 deaths at mean follow-up of 42.0 ± 27.6 months, none related to the procedure. Overnight stay costs £350; the same-day ablation policy over this period would have saved £310,450.
Conclusions
Same-day complex left-atrial catheter ablation using conscious sedation is safe and cost-effective with significant benefits for patients and healthcare providers. This is especially important in the current financial climate and Covid-19 pandemic.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 27 Sep 2020; epub ahead of print
He H, Datla S, Weight N, Raza S, ... Hayat S, Osman F
Int J Cardiol: 27 Sep 2020; epub ahead of print | PMID: 33002522
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Abstract

Prognostic value of multiple cardiac magnetic resonance imaging parameters in patients with idiopathic dilated cardiomyopathy.

Fu H, Wen L, Xu H, Liu H, ... Yang Z, Guo Y
Purpose
Our study aimed to comprehensively explore efficient prognostic indicators in idiopathic dilated cardiomyopathy (IDCM) patients with reduced left ventricular ejection fraction (LVEF<40%).
Background
Prognostic value of cardiac magnetic resonance(CMR) parameters for IDCM have been inconsistent.
Methods
126 IDCM patients with reduced LVEF (<40%) were retrospectively enrolled. Cardiac function parameters, myocardial strain indices and myocardial fibrosis were evaluated. Laboratory data also were analyzed. The endpoint was a combination of major adverse cardiac events (MACEs), including cardiac death, heart transplantation, and rehospitalization. Prognostic value was evaluated by the Kaplan-Meier method and Cox regression.
Results
During a median follow-up of 31 months, 44 patients experienced MACEs, including 9 deaths, 1 heart transplantation, and 34 rehospitalizations due to heart failure. Univariate and multivariate Cox analyses showed that cardiac function and myocardial strain indexes were not associated with the prognosis of IDCM (all p > 0.05). NT-proBNP (HR 1.5, 95%CI: 1.053 to 2.137), Late‑gadolinium enhancement(LGE) mass (HR 1.022, 95%CI: 1.005 to 1.038), and LGE mass/left ventricle mass were significant predictors (HR 1.027, 95%CI: 1.007 to 1.046) for MACEs, all p < 0.05. Besides, poorest prognosis was observed in IDCM patients with positive LGE combined with NT-proBNP (log-rank = 27.261, p ≤ 0.001).
Conclusion
NT-proBNP and extent of LGE were reliable predictors in IDCM patients with reduced LVEF. Additionally, presence of LGE combined with NT-proBNP showed the strongest prognostic value in IDCM with reduced LVEF. Myocardial strain parameters seemed to have no prognostic value in IDCM patients with reduced LVEF.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 06 Oct 2020; epub ahead of print
Fu H, Wen L, Xu H, Liu H, ... Yang Z, Guo Y
Int J Cardiol: 06 Oct 2020; epub ahead of print | PMID: 33038407
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Abstract

Serial changes in longitudinal strain are associated with outcome in children with hypoplastic left heart syndrome.

Borrelli N, Di Salvo G, Sabatino J, Ibrahim A, ... Fraisse A, Michielon G
Introduction
Hypoplastic Left Heart Syndrome (HLHS) has high mortality and morbidity and systemic right ventricle (RV) dysfunction may play a key-role. Study aim is to evaluate the accuracy of speckle-tracking echocardiographic (STE) assessment of RV deformation and 2D standard echo parameters in predicting outcome in HLHS patients.
Methods
We studied 27 HLHS patients (17 male) who successfully completed Norwood palliation. All the patients underwent in-hospital interstage stay. Serial echocardiographic assessment was performed: baseline, one-month after Norwood, three-months after Norwood, one-week before bidirectional cavopulmonary anastomosis (BCPA) and two-months after BCPA. From the apical view we measured: tricuspid annulus peak systolic excursion (TAPSE), fractional area change (FAC), longitudinal strain (LS) and strain rate (LSR).
Results
After a mean follow-up of 1.18 (± 1.16) years, 8 out of 27 of the included patients met the composite endpoint of death/heart transplant (HT). At pre-Norwood assessment, there was no difference in echo measurements between survivors and patients with events. In death/HT group TAPSE and LS declined already one-month after Norwood procedure: TAPSE ≤5 mm had good sensitivity (85.71%) and moderate specificity (63.16%) for death/HT (AUC = 0.767); a decrease of LS > 8.7% vs baseline showed 100% sensitivity and 84.21% specificity for death/HT (AUC = 0.910). At multivariate analysis, one-month-after-Norwood LS drop >8.7% was the best predictor of outcome (P = 0.01).
Conclusions
RV dysfunction in HLHS carries prognostic value. Our findings encourage serial measurements of RV function to identify the subgroup of HLHS patients at higher risk. In our experience, ∆ LS showed the best predictive value.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Oct 2020; 317:56-62
Borrelli N, Di Salvo G, Sabatino J, Ibrahim A, ... Fraisse A, Michielon G
Int J Cardiol: 14 Oct 2020; 317:56-62 | PMID: 32505372
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Abstract

Intra-day change in occurrence of out-of-hospital ventricular fibrillation in Japan: The JCS-ReSS study.

Otsuki S, Aiba T, Tahara Y, Nakajima K, ... Kusano K,
Background
Real-world evidence of out-of-hospital ventricular fibrillation (VF), especially regarding intra-day change, remains unclear. We aimed to investigate that age- and gender-dependent difference of intra-day change of VF occurrence.
Method
We enrolled 71,692 patients (males: 56,419 [78.7%], females: 15,273 [21.3%]) in whom cardiac VF had been documented from the 2005-2015 All-Japan Utstein Registry data. Subjects were divided into four groups: group-I (<18 years old), group-II (18-39), group-III (40-69), and group-IV (≥70). Among four groups in each of male and female, we compared the intra-day change of VF occurrence, and evaluated the risk factors of the unfavorable neurologic outcomes at 1 month after VF.
Results
Regardless of age, the incidence of VF was significantly greater in male than in female subjects. In male subjects, VF in group-I, III and IV occurred higher at daytime, however, group-II had no intra-day difference because group-II had a higher VF events at midnight~ early morning compared with other aged groups (Poisson regression analysis, p = .03). While in female, each group showed similar intra-day pattern of VF occurrence. Logistic regression analysis revealed that some of the clinical parameters such as time periods from call receipt to first shock and the presence of bystander cardiopulmonary resuscitation were important for risk of 30-day neurologically unfavorable outcomes.
Conclusions
The intra-day change of VF occurrence was age-dependently different in males but not in females, suggesting age- and gender-dependent differences in underlying cardiac diseases. These might affect the significant difference in unfavorable neurologic outcome.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 31 Oct 2020; 318:54-60
Otsuki S, Aiba T, Tahara Y, Nakajima K, ... Kusano K,
Int J Cardiol: 31 Oct 2020; 318:54-60 | PMID: 32569698
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Abstract

Thromboembolic and bleeding risk in obese patients with atrial fibrillation according to different anticoagulation strategies.

Patti G, Pecen L, Manu MC, Huber K, ... Kirchhof P, Caterina R
Background
Data on the relationship between body mass index (BMI), thromboembolic events (TEE) and bleeding in patients with atrial fibrillation (AF) are controversial, and further evidence on the risk of such events in obese patients with AF receiving different anticoagulant therapies (OAC) is needed.
Methods and results
We divided a total of 9330 participants from the prospective PREFER in AF and PREFER in AF PROLONGATION registries into BMI quartiles at baseline. Outcome measures were TEE and major bleeding complications at the 1-year follow-up. Without OAC, there was a ≥6-fold increase of TEE in the 4th vs other BMI quartiles (P = .019). OAC equalized the rates of TEE across different BMI strata. The occurrence of major bleeding was highest in patients with BMI in the 1st as well as in the 4th BMI quartile [OR 1.69, 95% CI 1.03-2.78, P = .039 and OR 1.86, 95% CI 1.13-3.04, P = .014 vs those in the 3rd quartile, respectively]. At propensity score-adjusted analysis, the incidence of TEE and major bleeding in obese patients receiving non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K-antagonist anticoagulants (VKAs) was similar (P ≥ .34).
Conclusions
Our real-world data suggest no obesity paradox for TEE in patients with AF. Obese patients are at higher risk of TEE, and here OAC dramatically reduces the risk of events. We here found a comparable clinical outcome with NOACs and VKAs in obese patients. Low body weight and obesity were also associated with bleeding, and therefore OAC with the best safety profile should be considered in this setting.

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

Int J Cardiol: 31 Oct 2020; 318:67-73
Patti G, Pecen L, Manu MC, Huber K, ... Kirchhof P, Caterina R
Int J Cardiol: 31 Oct 2020; 318:67-73 | PMID: 32574823
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Abstract

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

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

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 24 Sep 2020; epub ahead of print
Surkova E, Segura T, Dimopouosl K, Bispo D, ... Gatzoulis MA, Li W
Int J Cardiol: 24 Sep 2020; epub ahead of print | PMID: 32987051
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Abstract

Prevalence and incidence of various Cancer subtypes in patients with heart failure vs matched controls.

Schwartz B, Schou M, Gislason GH, Køber L, Torp-Pedersen C, Andersson C
Background
Patients with heart failure (HF) may be at increased risks of cancer, but the magnitude of risk for various cancer subtypes is insufficiently investigated.
Method
Using the Danish Nationwide administrative databases between 1997 and 2017, we estimated the prevalence, incidence and relative risk for all-cause cancer in new-diagnosed HF vs. age and sex-matched controls (up to 5 controls per HF case) before and after adjustment for comorbidities.
Results
Among the 167,633 people in the heart failure group and 837,126 individuals in the control group, there was a higher prevalence of several comorbidities, including cancer (17% vs. 10%) in the HF group; odds ratio 1.72 (1.70-1.75). Patients with heart failure also had higher cancer incidence (cancer incidence rate 3.02 [2.97-3.07] per 100 person-years), compared with controls (cancer incidence rate 1.89 [1.88-1.90]); hazards ratio 1.38 (1.36-1.40). However, after adjustment for comorbidities the increased risk of malignancy was greatly attenuated (hazards ratio 1.14 [1.12-1.16] for incident all-cause cancer) and dissipated altogether after additional adjustment for medications (multivariable adjusted hazards ratio 0.93 [0.91-0.96] for all-cause cancer). In a homogeneous cohort of patients with ischemic heart disease, the increased risk of all-cause cancer was only marginally increased after adjustment for baseline comorbidities (hazards ratio 1.05 [1.02-1.08]).
Conclusion
Patients with heart failure had a slightly increased risk of various cancer subtypes, but the risks were mainly driven by comorbidities.

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

Int J Cardiol: 30 Sep 2020; 316:209-213
Schwartz B, Schou M, Gislason GH, Køber L, Torp-Pedersen C, Andersson C
Int J Cardiol: 30 Sep 2020; 316:209-213 | PMID: 32446924
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Abstract

Clinical significance of diastolic late mitral annular velocity in heart failure with preserved ejection fraction.

Oike F, Yamamoto E, Sueta D, Tokitsu T, ... Kaikita K, Tsujita K
Objectives
Because diastolic late mitral annular velocity (a\') obtained by transthoracic-echocardiography (TTE) represents left atrial (LA) function, we investigated the clinical significance of a\' in heart failure (HF) with a preserved left ventricular (LV) ejection fraction (HFpEF).
Methods
We enrolled 448 consecutive HFpEF patients (sinus rhythm: 66.3%, atrial fibrillation [AF] rhythm: 33.7%) and performed TTE under stable conditions after optimal therapy. In patients with sinus rhythm, a\' values were measured at septal mitral annuli.
Results
A\' had weak but significant negative correlations with the natural-logarithm-B-type natriuretic peptide (Ln-BNP), LA diameter, LV mass index and tricuspid regurgitation pressure gradient. Receiver operating characteristic (ROC) curve analysis showed that the best cut-off value of a\' and systolic mitral annular velocity (s\') for the prediction of HF-related events were 7.45 cm/s and 6.5 cm/s with areas under the curve (AUC) of 0.841 and 0.682, respectively. The AUC of ROC analysis for the logistic regression model of a\' plus s\' was improved to 0.97. In Kaplan-Meier analysis, HFpEF patients with low-a\' (<7.45 cm/s) had a significantly higher risk of total cardiovascular and HF-related events (both p < .01 by log-rank test) than those with high-a\' (≥ 7.45 cm/s) and were prognostically equivalent to those with AF. Multivariate Cox proportional hazard analysis identified low-a\' as an independent predictor of both total cardiovascular (hazard ratio [HR]: 0.823, 95% confidence interval [CI]: 0.714-0.949, p = .007) and HF-related events (HR: 0.551, 95% CI: 0.422-0.720, p < .001).
Conclusion
A\' value measurement is a non-invasive and useful method for risk stratification in HFpEF.

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

Int J Cardiol: 30 Sep 2020; 316:145-151
Oike F, Yamamoto E, Sueta D, Tokitsu T, ... Kaikita K, Tsujita K
Int J Cardiol: 30 Sep 2020; 316:145-151 | PMID: 32507393
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Impact:
Abstract

Blockade of the neurohormonal systems in heart failure with preserved ejection fraction: A contemporary meta-analysis.

Gallo G, Tocci G, Fogacci F, Battistoni A, Rubattu S, Volpe M
Background
Although individual studies failed to demonstrate significant benefits with neurohormonal inhibitors in patients affected by heart failure (HF) with preserved ejection fraction (HFpEF), an evident trend towards a reduction in hospitalization and mortality has been previously documented in most cases. We aimed to conduct an updated meta-analysis on the effect of neurohormonal inhibitors [renin-angiotensin-aldosterone system (RAAS) inhibitors and angiotensin receptor neprilysin inhibitors (ARNi)] on the primary composite outcome of mortality and hospitalizations for HF and on the secondary outcomes of mortality and hospitalizations separately analyzed.
Methods and results
The extended literature search ended up with the identification of a total of 12 studies cumulatively including 30,882 patients, 16,540 in the treatment and 14,432 in the control groups. Eleven studies explored the outcome of death, 9 studies reported data about HF hospitalizations and 8 studies explored the composite outcome of death and HF hospitalizations. Our meta-analysis showed that treatment with neurohormonal inhibitors was significantly associated with a reduced risk of the primary composite outcome (OR 0.87, 95%CI: 0.82-0.93, p < .001; I = 2.2.) and with a decreased risk of HF hospitalizations (OR 0.84, 95%CI: 0.75-0.94, p = .002; I = 63%). In contrast, no significant effect on death was found (OR 0.79, 95%CI: 0.55-1.12, p = .184; I = 96.4%). Results remained substantially unchanged in the leave-one-out sensitivity analysis.
Conclusion
Our current work supports a beneficial effect of neurohormonal inhibitors (RAAS blockers and ARNi) on the primary composite outcome of death and HF hospitalizations and on the secondary outcome of HF hospitalizations in HFpEF patients. This finding provides support to the current prevalent clinical approach and to level of evidence reported in the Guidelines.

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

Int J Cardiol: 30 Sep 2020; 316:172-179
Gallo G, Tocci G, Fogacci F, Battistoni A, Rubattu S, Volpe M
Int J Cardiol: 30 Sep 2020; 316:172-179 | PMID: 32522678
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Impact:
Abstract

Measurement, consequences and determinants of time to diagnosis in children with new-onset heart failure: A population-based retrospective study (DIACARD study).

Bichali S, Malorey D, Benbrik N, Le Gloan L, ... Baruteau AE, Launay E
Background
Time from first symptoms to diagnosis, called time to diagnosis, is related to prognosis in several diseases. The aim of this study was to assess time to diagnosis in children with new-onset heart failure (HF) and assess its consequences and determinants.
Methods
A retrospective population-based observational study was conducted between 2007 and 2016 in a French tertiary care center. We included all children under 16 years old with no known heart disease, and HF confirmed by echocardiography. With logistic regression used for outcomes and a Cox proportional-hazards model for determinants, analyses were stratified by HF etiology: congenital heart diseases (CHD) and cardiomyopathies/myocarditis (CM).
Results
A total of 117 children were included (median age [interquartile range (IQR)] 25 days (6-146), 50.4% were male, 60 had CHD and 57 had CM). Overall median (IQR) time to diagnosis was 3.3 days (1.0-21.2). The frequency of 1-year mortality was 17% and 1-year neuromotor sequel 18%. Death at 1 year was associated with low birth weight for all patients (adjusted odds ratio 0.24, 95% confidence interval [CI] 0.08-0.68) and time to diagnosis below the median with CM (0.09, 0.01-0.87) but not time to diagnosis above the median for all patients (0.59, 0.13-2.66). Short time to diagnosis was associated with clinical severity on the first day of symptoms for all patients (adjusted hazard ratio 3.39, 95% CI 2.01-5.72), and young age with CM (0.09, 0.02-0.41).
Conclusions
In children with new-onset HF presenting in our region, median time to diagnosis was short. Long time to diagnosis was not associated with poor outcome.

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

Int J Cardiol: 31 Oct 2020; 318:87-93
Bichali S, Malorey D, Benbrik N, Le Gloan L, ... Baruteau AE, Launay E
Int J Cardiol: 31 Oct 2020; 318:87-93 | PMID: 32553597
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Impact:
Abstract

Cardiopulmonary exercise testing in chronic heart failure patients treated with beta-blockers: Still a valid prognostic tool.

Corrà U, Giordano A, Piepoli M
Background
The advent of beta-blockers (BBs) has revolutionized the treatment of heart failure due to left ventricular dysfunction (HFrEF), as these drugs increase survival and reduce hospitalization without a significant impact on exercise tolerance. In this new prognostic scenario, the predictive role of cardiopulmonary exercise testing (CPET) has been questioned.
Aim
To evaluate the predictive value of CPET and \"traditional\" derived and calculated risk parameters in HFrEF patients on BBs.
Methods
We retrospectively correlated 17 CPET risk parameters with hard events (cardiac death or urgent heart transplantation) over a 3-year follow-up in 744 HFrEF patients treated with BBs at our Institute from 2000 to 2013.
Results
Events were observed in 121/744 (16%) patients. Most CPET parameters were related to outcome at univariable analysis, but at multivariable analysis only exertional oscillatory ventilation (EOV), peak systolic blood pressure (SBP) and percentage of predicted peak VO2 (VO2%) resulted as significant. A CPET model using the dichotomized cut-off values of peak SPB ≤ 140 mmHg (HR = 2,27, p = .000, CI = 0.58-3.85), peak VO2% ≤ 50% (HR = 1.65, p = .008, CI = 1.14-2.38) and EOV = yes had a likelihood ratio of 45.27 (p = .000).
Conclusions
CPET confirmed its value as a prognostic tool in HFrEF patients treated with BBs, but different CPET parameters emerged as predictive (EOV, peak VO2% and peak SBP).

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Oct 2020; 317:128-132
Corrà U, Giordano A, Piepoli M
Int J Cardiol: 14 Oct 2020; 317:128-132 | PMID: 32611497
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Impact:
Abstract

Impact of the CHADS-VASc score on late clinical outcomes in patients undergoing left atrial appendage occlusion.

Agudelo V, Millán X, Li CH, Asmarats L, ... Serra A, Arzamendi D
Background
Left atrial appendage occlusion (LAAO) is an accepted strategy for cardioembolic events prevention in patients with non-valvular atrial fibrillation (AF) unsuitable for anticoagulation. However, uncertainties persist regarding the benefit of LAAO in highly-comorbid patients. The aim of this study was to assess the impact of the CHADS-VASc score beyond thromboembolic risk in predicting clinical outcomes in patients undergoing LAAO.
Methods
160 patients who underwent LAAO were included and categorized into two groups according to their stroke risk (89 with CHADS-VASc >4 vs. 71 with lower risk). The coprimary endpoints were death and stroke at follow-up. Thromboembolic and bleeding events were compared to those predicted from CHADS-VASc and HAS-BLED scores.
Results
Over a median follow-up of 679 days, CHADS-VASc >4 was associated with increased all-cause mortality compared with patients with lower thromboembolic risk (HR: 3.23; 95% CI: 1.28-8.19; p < 0.001). However, the rates of stroke after LAAO were not significantly different between risk groups. The observed annual rates of stroke and major bleeding were lower than predicted.
Conclusions
Despite increased long-term mortality in patients with CHADS-VASc >4, LAAO remains beneficial in reducing stroke and bleeding events in high-risk AF patients unsuitable for anticoagulation.

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

Int J Cardiol: 14 Nov 2020; 319:78-84
Agudelo V, Millán X, Li CH, Asmarats L, ... Serra A, Arzamendi D
Int J Cardiol: 14 Nov 2020; 319:78-84 | PMID: 32634500
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Impact:
Abstract

Blood carbon dioxide tension and risk in pulmonary arterial hypertension.

Harbaum L, Fuge J, Kamp JC, Hennigs JK, ... Hoeper MM, Klose H
Background
Low partial pressure of blood carbon dioxide (PCO) is common in patients with pulmonary arterial hypertension (PAH) and may inform on clinical outcomes. We investigated whether PCO measurements could provide prognostic information in addition to standard risk assessment in this group of patients.
Methods
We conducted a retrospective observational cohort study on patients with newly diagnosed idiopathic, heritable or drug/toxin-induced PAH recruited from two European centres. Arterialised capillary blood gas analyses at diagnosis and follow-up were incorporated into standard risk assessment strategies and related to outcomes, defined as lung transplant or death. C statistics from receiver-operated characteristics and Cox regression models were used to assess the predictive value of models with and without PCO measurements. Unsupervised clustering was applied to assess the relation of PCO to haemodynamic and pulmonary function variables.
Results
Low PCO measured at diagnosis and follow-up was significantly associated with inferior outcomes in 204 patients with PAH. PCO provided prognostic information independent of established non-invasive variables. Integrating PCO in risk strata improved C statistics of non-invasive and mixed invasive/non-invasive models, and revealed more accurate outcome estimates in regression models. Pairwise correlation and unsupervised cluster analyses supported a link between PCO and haemodynamic variables, particularly with cardiac output, in PAH.
Conclusions
Measuring PCO at diagnosis and during follow-up in patients with PAH provided independent prognostic information and has the potential to improve current risk assessment strategies.

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

Int J Cardiol: 31 Oct 2020; 318:131-137
Harbaum L, Fuge J, Kamp JC, Hennigs JK, ... Hoeper MM, Klose H
Int J Cardiol: 31 Oct 2020; 318:131-137 | PMID: 32634498
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Impact:
Abstract

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

Wada T, Shiono Y, Kubo T, Honda K, ... Nishimura Y, Akasaka T
Background
We aimed to assess an impact of instantaneous wave-free ratio (iFR) on a graft failure after coronary artery bypass grafting (CABG).
Methods and results
A total of 131 coronary arteries from 88 patients who underwent invasive coronary angiography, intracoronary pressure measurements, CABG, and scheduled follow-up coronary computed tomography angiography within one year were investigated. All studied arteries had FFR <0.80. The rate of graft failure was significantly higher in vessels with the negative iFR (>0.89) than in those with positive iFR (<0.89) (25.7% vs. 7.3%, p = 0.0012). The graft failure rates increased as the preoperative iFR values rose (iFR <0.80, 3.3%; iFR: 0.80-0.84, 5.6%; iFR: 0.85-0.89, 16.0%; iFR: 0.90-0.94, 28.0%; and iFR: 0.95-1.00, 50.0%; p = 0.0018). A cut-off value of iFR to predict graft failures was determined as 0.84 by receiver-operating characteristic curve analysis with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 88%, 62%, 25%, 97%, and 66%, respectively.
Conclusions
The risk of graft failure becomes higher, as the preoperative iFR increases. The graft failure is significantly more frequent when a bypass graft is anastomosed on vessels with negative iFR than those with positive iFR.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 19 Sep 2020; epub ahead of print
Wada T, Shiono Y, Kubo T, Honda K, ... Nishimura Y, Akasaka T
Int J Cardiol: 19 Sep 2020; epub ahead of print | PMID: 32966833
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Impact:
Abstract

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

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

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 28 Sep 2020; epub ahead of print
Shibata N, Kondo T, Kazama S, Kimura Y, ... Shimizu K, Murohara T
Int J Cardiol: 28 Sep 2020; epub ahead of print | PMID: 33007325
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Impact:
Abstract

Are left atrial diverticula and left-sided septal pouches relevant additional findings in cardiac CT? Correlation between left atrial outpouching structures and ischemic brain alterations.

Celik E, Pennig L, Laukamp KR, Hammes J, ... Caldeira L, Hickethier T
Purpose
To evaluate the correlation between left atrial diverticula (LAD) and left-sided septal pouches (LSSP) with ischemic brain alterations in MRI.
Methods
A retrospective analysis of 174 patients who received both, a dedicated cardiac CT angiography (CCTA) and a brain MRI examination was performed. Two radiologists independently reviewed all examinations for the presence of LAD and LSSP as well as ischemic alterations of the brain. Subsequently, the correlation between these cardiac and cerebral findings as well as to other potentially related risk factors was assessed.
Results
71 LAD (total prevalence 41%) and 65 LSSP (total prevalence 37%) were identified in 174 patients. Combined prevalence was 10%. Ischemic brain alterations were found in patients with a LAD in 42.3% (30/71) and with a LSSP in 64.6% (42/65). Patients without any anatomical variant in the left atrium showed ischemic brain alterations in 39.4% (26/66). The presence of a LSSP was associated with an increased risk for ischemic brain alterations in multivariate logistic regression analysis after adjusting for other risk factors (OR = 3.57, 95% CI = 0.51-2.09, p <  .01).
Conclusion
In our study cohort LAD and LSSP are highly prevalent anatomical structures within the left atrium. Patients with LSSP showed an approximated 3.5-fold higher probability for ischemic brain alterations. Therefore, LSSP should be considered as a potential risk factor for cardioembolic strokes and its presence should be stated in cardiac CT reports.

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

Int J Cardiol: 14 Oct 2020; 317:216-220
Celik E, Pennig L, Laukamp KR, Hammes J, ... Caldeira L, Hickethier T
Int J Cardiol: 14 Oct 2020; 317:216-220 | PMID: 32461119
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Impact:
Abstract

Prevalence of left ventricular hypertrabeculation/noncompaction among patients with congenital dyserythropoietic anemia Type 1 (CDA1).

Abramovich-Yoffe H, Shalev A, Barrett O, Shalev H, Levitas A
Background
Congenital dyserythropoietic anemia type 1 (CDA1) is a rare autosomal recessive disease characterized by macrocytic anemia, ineffective erythropoiesis, and secondary hemochromatosis. Left-ventricular noncompaction (LVNC) is a cardiomyopathy that is commonly attributed to intrauterine arrest of normal compaction during the endomyocardial morphogenesis. LV hypertrabeculation/noncompaction (LVHT/NC) morphology, however, might exist in various hemoglobinopathies. Our primary objective was to determine whether the pattern of LVHT/NC is more prevalent among patients with CDA1, in comparison to subjects without CDA1, and to find potential risk factors for LVHT/NC among these patients. Our secondary objective was to evaluate the clinical implication of LVHT/NC.
Methods
We retrospectively assessed 32 CDA1 patients (median age 17.5, range 6-61) that underwent routine assessment of iron overload by cardiac magnetic resonance. Number and distribution of noncompacted LV segments were assessed in CDA1 patients and compared to 64 age- and gender-matched patients without CDA1. The ratio of noncompacted to compacted myocardium (NC/C ratio) in end-diastole was calculated for each of the three long-axis views. NC/C ratio > 2.3 was considered diagnostic for LVHT/NC.
Results
In multivariate analysis, the presence of CDA1 was independently associated with NC/C ratio > 2.3, a feature of LVHT/NC (adjusted OR = 11.46, 95%CI = 2.6-50.68, p = .001). CDA1 was strongly associated with increased number of myocardial segments exhibiting LVHT/NC pattern. Cardiac volumes and ejection fraction were preserved without clinical adverse events in long term follow-up.
Conclusions
CDA1 patients have a higher prevalence of LVHT/NC than normal individuals, independent of myocardial iron overload and without effect on ejection fraction or clinical outcome.

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

Int J Cardiol: 14 Oct 2020; 317:96-102
Abramovich-Yoffe H, Shalev A, Barrett O, Shalev H, Levitas A
Int J Cardiol: 14 Oct 2020; 317:96-102 | PMID: 32512057
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Impact:
Abstract

Commentary: Temporarily omitting oral anticoagulants early after stenting for acute coronary syndromes patients with atrial fibrillation.

Limbruno U, Goette A, De Caterina R

The joint occurrence of atrial fibrillation (AF) and an acute coronary syndrome (ACS) entails a three-dimensional - cardioembolic, coronary and hemorrhagic - risk. Triple antithrombotic therapy (TAT), i.e., oral anticoagulation (OAC) on top of dual antiplatelet therapy (DAPT), has been the default strategy for such patients until recently. Due to the high hemorrhagic burden of TAT, several dual antithrombotic therapy (DAT) regimens, i.e., OAC plus a single antiplatelet agent, have been proposed in randomized trials with the aim of improving safety without hampering efficacy. Current guidelines and consensus documents still leave here, however, OAC as an undisputed cornerstone. Such documents do not sufficiently distinguish between the ischemic risk due to ACS treated with stenting and the one due to AF, which may dissociate in some patients and definitely have a different time course. The possibility of postponing the introduction of OAC in such conditions, rather taking advantage of the use of newer P2Y inhibitors prasugrel and ticagrelor, is not currently sufficiently contemplated in contemporary documents. We here question the claimed lack of alternatives to the \"anticoagulant always and immediately\" approach in most such patients, propose some risk simulations, claim that skipping anticoagulation in the presence of modern DAPT for one month after an ACS in the context of a high bleeding risk and a high coronary risk is a valuable, currently unlisted option, and raise the need of a proper trial on this controversial issue.

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

Int J Cardiol: 31 Oct 2020; 318:82-85
Limbruno U, Goette A, De Caterina R
Int J Cardiol: 31 Oct 2020; 318:82-85 | PMID: 32389765
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Impact:
Abstract

Automated extraction of left atrial volumes from two-dimensional computer tomography images using a deep learning technique.

Chen HH, Liu CM, Chang SL, Chang PY, ... Chen SA, Lu HH
Background
Precise segmentation of the left atrium (LA) in computed tomography (CT) images constitutes a crucial preparatory step for catheter ablation in atrial fibrillation (AF). We aim to apply deep convolutional neural networks (DCNNs) to automate the LA detection/segmentation procedure and create three-dimensional (3D) geometries.
Methods
Five hundred eighteen patients who underwent procedures for circumferential isolation of four pulmonary veins were enrolled. Cardiac CT images (from 97 patients) were used to construct the LA detection and segmentation models. These images were reviewed by the cardiologists such that images containing the LA were identified/segmented as the ground truth for model training. Two DCNNs which incorporated transfer learning with the architectures of ResNet50/U-Net were trained for image-based LA classification/segmentation. The LA geometry created by the deep learning model was correlated to the outcomes of AF ablation.
Results
The LA detection model achieved an overall 99.0% prediction accuracy, as well as a sensitivity of 99.3% and a specificity of 98.7%. Moreover, the LA segmentation model achieved an intersection over union of 91.42%. The estimated mean LA volume of all the 518 patients studied herein with the deep learning model was 123.3 ± 40.4 ml. The greatest area under the curve with a LA volume of 139 ml yielded a positive predictive value of 85.5% without detectable AF episodes over a period of one year following ablation.
Conclusions
The deep learning provides an efficient and accurate way for automatic contouring and LA volume calculation based on the construction of the 3D LA geometry.

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

Int J Cardiol: 30 Sep 2020; 316:272-278
Chen HH, Liu CM, Chang SL, Chang PY, ... Chen SA, Lu HH
Int J Cardiol: 30 Sep 2020; 316:272-278 | PMID: 32507394
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Impact:
Abstract

Outcomes and predictors of cardiac events in medically treated patients with atrial functional mitral regurgitation.

Kim K, Kitai T, Kaji S, Pak M, ... Kinoshita M, Furukawa Y
Background
Little is known about the outcomes and predictors of adverse cardiac events in medically treated patients with atrial functional mitral regurgitation (FMR).
Methods
We screened 1405 consecutive patients with grade ≥ 3+ mitral regurgitation (MR) detected by echocardiography. After excluding patients with previous or early (within 3 months from diagnosis) mitral valve surgery, congenital heart disease, hypertrophic cardiomyopathy, severe aortic valve disease, or unknown etiology, the study population consisted of 319 patients with primary MR, 395 patients with FMR with left ventricular (LV) dysfunction, and 184 patients with atrial FMR. Atrial FMR was defined as FMR in patients without LV wall motion abnormality or dilatation.
Results
The cumulative incidence of the composite of cardiac death and heart failure hospitalization at 3 years was 10.5% in primary MR, 37.5% in FMR with LV dysfunction, and 14.0% in atrial FMR (p < .001). In atrial FMR patients, LV end-diastolic volume index (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.02-1.10), severe MR (grade 4+) (HR 2.73, 95% CI 1.21-6.12), being symptomatic (NYHA ≥ 2) (HR 2.82, 95% CI 1.15-6.92), and having ≥1 comorbidities (HR 3.96, 95% CI 1.74-9.00) were independently associated with an increased risk for adverse cardiac events by a multivariable Cox regression analysis.
Conclusions
Outcomes of medically treated patients with atrial FMR were better than those of FMR with LV dysfunction, but worse than those of primary MR. In atrial FMR patients, LV dilatation, severe MR, being symptomatic, and the presence of comorbidities were independently associated with an increased risk for adverse cardiac events.

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

Int J Cardiol: 30 Sep 2020; 316:195-202
Kim K, Kitai T, Kaji S, Pak M, ... Kinoshita M, Furukawa Y
Int J Cardiol: 30 Sep 2020; 316:195-202 | PMID: 32610155
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Impact:
Abstract

Effectiveness of alcohol septal ablation for hypertrophic obstructive cardiomyopathy in patients with late gadolinium enhancement on cardiac magnetic resonance.

Polaková E, Liebregts M, Marková N, Adla T, ... Bonaventura J, Veselka J
Background
According to European guidelines, alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM) may be less effective in patients with extensive septal scarring on cardiac magnetic resonance (CMR). This study aimed to analyze the impact of late gadolinium enhancement (LGE) on CMR on the effectiveness of ASA.
Method
We conducted an observational retrospective study involving adult patients with symptomatic drug-refractory HOCM who underwent CMR before ASA at two European centres from May 2010 through June 2019. Patients were compared in binary format based on LGE presence. Moreover, a subanalysis focused on patients with septal fibrosis was performed. The effectiveness of ASA was evaluated by echocardiographic, ECG and clinical findings.
Results
Of the 113 study patients, 54 (48%) had LGE on CMR. The LGE quantification performed in 29 patients revealed septal fibrosis in 17. The mean follow-up was 4.4 ± 2.6 years. Baseline parameters were similar between groups except for basal septal thickness that was greater in LGE+ group (21.1 ± 3.9 mm for LGE+ vs. 19.2 ± 3.2 mm for LGE-: p = .005). ASA improved symptoms in all groups and reduced left ventricular outflow tract obstruction (LVOTO) (delta gradient reduction: LGE+: 62 ± 37.3%; septal LGE+: 75.6 ± 20.8%; LGE-: 72.5 ± 21.0%). However, 13% of the LGE+ and 2% of the LGE- group had residual LVOTO above 30 mmHg (p = .027).
Conclusion
ASA was effective in all patients with HOCM, whether they had LGE on CMR or not and whether they had septal fibrosis or not.

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

Int J Cardiol: 14 Nov 2020; 319:101-105
Polaková E, Liebregts M, Marková N, Adla T, ... Bonaventura J, Veselka J
Int J Cardiol: 14 Nov 2020; 319:101-105 | PMID: 32682963
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Impact:
Abstract

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

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

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 01 Oct 2020; epub ahead of print
Liao LZ, Zhuang XD, Zhang SZ, Liao XX, Li WD
Int J Cardiol: 01 Oct 2020; epub ahead of print | PMID: 33017630
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Impact:
Abstract

Comparison of two biomarker only algorithms for early risk stratification in patients with suspected acute coronary syndrome.

Kavsak PA, Mondoux SE, Ma J, Sherbino J, ... Devereaux PJ, Worster A
Background
We developed a biomarker algorithm encompassing the clinical chemistry score (CCS; which includes the combination of a random glucose concentration, an estimated glomerular filtration rate and high-sensitivity cardiac troponin; hs-cTn) with the Ortho Clinical Diagnostics hs-cTnI assay (CCS-serial) and compared it to the cutoffs derived from Ortho Clinical Diagnostics 0/1 h (h) algorithm for 7-day myocardial infarction (MI) or cardiovascular (CV)-death.
Methods
The study cohort was an emergency department (ED) population (n = 906) with symptoms suggestive of acute coronary syndrome (ACS) who had two Ortho hs-cTnI results approximately 3 h apart. Diagnostic parameters (sensitivity/specificity/negative predictive value; NPV/positive predictive value; PPV) were derived for the CCS-serial and the 0/1 h algorithm for 7-day MI/CV-death. A safety analysis was performed for patients in the rule-out arms of the algorithms for 30-day MI/death.
Results
The CCS-serial algorithm yielded 100% sensitivity/NPV (32% low-risk) and 95.7% specificity/65% PPV (11% high-risk). The 0/1 h algorithm-cutoffs yielded sensitivity/NPV/specificity/PPV of 97.8%/99.4%/91.3%/50%, which classified 38% of patients as low-risk and 16% of patients as high-risk. Four patients (1.2%) in the 0/1 h algorithm-cutoff rule-out arm had a 30-day MI/death outcome as compared to zero patients in the CCS-serial rule-out arm (p = 0.06).
Conclusion
Both the CCS-serial and 0/1 h algorithm cutoffs yield high NPVs with a similar proportion of patients identified as low-risk. These data may be useful for sites who are unable to collect samples at 0/1 h in the emergency department.

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

Int J Cardiol: 14 Nov 2020; 319:140-143
Kavsak PA, Mondoux SE, Ma J, Sherbino J, ... Devereaux PJ, Worster A
Int J Cardiol: 14 Nov 2020; 319:140-143 | PMID: 32634494
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Impact:
Abstract

A review of global health technology assessments of non-VKA oral anticoagulants in non-valvular atrial fibrillation.

Lopes RD, Berger SE, Di Fusco M, Kang A, ... Deshpande S, Mantovani LG
Background
This review assessed global health technology assessment (HTA) reports and recommendations of non-vitamin K oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF).
Methods
NHTA agency websites were searched for HTA reports evaluating NOACs versus NOACs or vitamin K antagonists. HTA methods and information on patient involvement/access were collected and empirically analyzed.
Results
The review identified 38 unique HTA reports published between 2012 and 2017 in 16 countries including 11 in Europe. NOACs that were cost-effective per local willingness-to-pay (WTP) thresholds were positively recommended for the treatment of NVAF. WTP thresholds ranged from €20,000 to 69,000. Apixaban was recommended in 10/12 (83%) countries, dabigatran in 9/13 (69%) countries, and rivaroxaban in 10/13 (76%) over warfarin. Edoxaban was recommended in 5/7 (71%) countries. Economic evaluations and recommendations comparing NOACs were sparse (two or three countries per NOAC) and generally favored apixaban and edoxaban, followed by dabigatran. Eleven HTA reports from four countries considered the patient voice (Canada [n = 3], Scotland [n = 3], England [n = 4], Brazil [n = 1]); however, only 2/11 (18%) developed recommendations based on this. Among the reports with a positive recommendation, 26/30 (87%) featured a decision that aligned with the approved regulatory label.
Conclusions
Most agencies recommended NOACs over warfarin for patients with NVAF. Few countries made statements recommending one NOAC over another. Given different WTP thresholds, a drug that is cost-effective in one market may not be in another. Therefore, the various NOAC recommendations from HTA agencies cannot be generalized across different countries.

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

Int J Cardiol: 14 Nov 2020; 319:85-93
Lopes RD, Berger SE, Di Fusco M, Kang A, ... Deshpande S, Mantovani LG
Int J Cardiol: 14 Nov 2020; 319:85-93 | PMID: 32634487
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Impact:
Abstract

Long-term outcome of prosthesis-patient mismatch after transcatheter aortic valve replacement.

Compagnone M, Marchetti G, Taglieri N, Ghetti G, ... Galiè N, Saia F
Background
Incidence and long-term clinical consequences of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) are still unclear.
Methods
We enrolled 710 consecutive patients who underwent TAVR. PPM was defined as absent if the index orifice area (iEOA) was >0.85 cm2/m2, moderate if the iEOA was between 0.65 and 0.85 cm2/m2 or severe if the iEOA was <0.65 cm2/m2.
Results
Among the 566 patients fulfilling the study criteria, the distribution of PPM was as follows: 50.5% none (n = 286), 43% moderate PPM (n = 243) and 6.5% severe PPM (n = 37). At 5-year follow-up, patients with severe PPM had a significantly higher incidence of the combined endpoint of cardiovascular death, acute myocardial infarction and stroke (p = .025) compared with the other patients. After adjusting the results for possible confounders, severe PPM remained an independent predictor of long-term adverse outcome (HR: 2.46; 95% Confidence Interval: 1.10-5.53). The independent predictors of severe PPM were valve-in-valve procedure and body mass index. Balloon-expandable valves were not associated with higher rates of severe PPM in comparison with self-expandable valves (8% vs. 5%, respectively, p = .245).
Conclusions
In our study severe PPM emerged as a risk factor for long-term major adverse cardiac and cerebrovascular events.

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

Int J Cardiol: 31 Oct 2020; 318:27-31
Compagnone M, Marchetti G, Taglieri N, Ghetti G, ... Galiè N, Saia F
Int J Cardiol: 31 Oct 2020; 318:27-31 | PMID: 32640260
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Impact:
Abstract

Mon2-monocytes and increased CD-11b expression before transcatheter aortic valve implantation are associated with earlier death.

Pfluecke C, Wydra S, Berndt K, Tarnowski D, ... Linke A, Ibrahim K
Background
In the first three months after Transcatheter aortic valve implantation (TAVI), a remarkable number of patients have an unfavorable outcome. An inflammatory response after TAVI is suspected to have negative effects. The exact mechanisms remain unclear. We examined the influence of monocyte subpopulations on the clinical outcome, along with the degree of monocyte activation and further parameters of inflammation and platelet activation.
Methods
Flow-cytometric quantification analyses of peripheral blood were done in 120 consecutive patients who underwent TAVI (one day before TAVI and on day 1 and 7 after TAVI). Monocyte-subsets were defined by their CD14 and CD16 expression, monocyte-platelet-aggregates (MPA) by CD14/CD41 co-expression. The extent of monocyte activation was determined by quantification of CD11b-expression (activation epitope). Additionally, pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, C-reactive protein were measured with the cytometric bead array method or standard laboratory tests.
Results
Elevated Mon2 (CD14CD16) - monocytes (38 vs. 62 cells/μl, p < 0.001) and a high expression of CD11b prior to TAVI (MFI 50.1 vs. 84.6, p < 0.05) were independently associated with death 3 months after TAVI. Mon2 showed the highest CD11b-expression and CD11b correlated with platelet activation and markers of systemic inflammation. Even CRP and IL-8 before TAVI were associated with death after TAVI. In contrast, a systemic inflammation response shortly after TAVI was not associated with early death.
Conclusions
Elevated Mon2-monocytes and a high level of monocyte activation before TAVI are associated with early mortality after TAVI. Chronic inflammation in aging patients seems to be an important risk factor after TAVI.

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

Int J Cardiol: 31 Oct 2020; 318:115-120
Pfluecke C, Wydra S, Berndt K, Tarnowski D, ... Linke A, Ibrahim K
Int J Cardiol: 31 Oct 2020; 318:115-120 | PMID: 32413468
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Impact:
Abstract

Diffuse coronary artery dilation predicted worse long-term outcomes in patients with coronary artery Ectasia.

Cai Z, Liu J, Wang H, Yin D, Song W, Dou K
Background
Coronary artery ectasia (CAE) is a rare finding in coronary angiography and associated with worse clinical outcomes. According to the extent of the dilated lesions, CAE is classified into diffuse and focal dilation. The difference in clinical outcomes between these 2 phenotypes remains unknown.
Methods
A cohort study was conducted comprising CAE patients identified by coronary angiography between January 2009 to December 2013. Follow-up was proceeded annually and the primary outcome was major adverse cardiovascular events (MACE) defined as a component of cardiovascular death and nonfatal myocardial infarction(MI). Kaplan-Meier method and Cox regression models were used to assess the clinical outcomes in diffuse CAE group and focal CAE group. Propensity score matching, propensity score weighting, and subgroup analysis were performed as sensitivity analysis.
Results
A total of 595 patients were included in this study, including 474 individuals with diffuse CAE and 121 with focal CAE. During a median follow-up of 87 months, Patients in diffuse CAE group showed significantly higher incidences of MACE (13.1% vs. 3.3%;HR 4.28, 95%CI 1.56-11.78, P = .005), as well as cardiovascular death (7.0% vs. 1.7%;HR 4.41, 95%CI 1.06-18.39, P = .041). Higher occurrence rate of MACE was consistent in propensity score matched cohort and propensity score weighted analysis. The same trend towards increased risk of MACE in diffuse CAE group was obtained among subgroup analysis.
Conclusions
Patients with diffuse CAE was associated with increased risk of MACE compared to those with focal CAE. Diffuse dilation found in coronary angiography should receive more attention by physicians.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Nov 2020; 319:20-25
Cai Z, Liu J, Wang H, Yin D, Song W, Dou K
Int J Cardiol: 14 Nov 2020; 319:20-25 | PMID: 32504718
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Impact:
Abstract

Blood transfusion and ischaemic outcomes according to anemia and bleeding in patients with non-ST-segment elevation acute coronary syndromes: Insights from the TAO randomized clinical trial.

Deharo P, Ducrocq G, Bode C, Cohen M, ... Elbez Y, Steg PG
Background
The benefits and risks of blood transfusion in patients with acute myocardial infarction who are anemic or who experience bleeding are debated. We sought to study the association between blood transfusion and ischemic outcomes according to haemoglobin nadir and bleeding status in patients with NST-elevation myocardial infarction (NSTEMI).
Methods
The TAO trial randomized patients with NSTEMI and coronary angiogram scheduled within 72h to heparin plus eptifibatide versus otamixaban. After exclusion of patients who underwent coronary artery bypass surgery, patients were categorized according to transfusion status considering transfusion as a time-varying covariate. The primary ischemic outcome was the composite of all-cause death or MI within 180 days of randomization. Subgroup analyses were performed according to pre-transfusion hemoglobin nadir and bleeding status.
Results
12,547 patients were enrolled. Among these, blood transfusion was used in 489 (3.9%) patients. Patients who received transfusion had a higher rate of death or MI (29.9% vs. 8.1%, p<0.01). This excess risk persisted after adjustment on GRACE score and nadir of hemoglobin (HR 3.36 95%CI 2.63-4.29 p<0.01). Subgroup analyses showed that blood transfusion was associated with a higher risk in patients without overt bleeding (adjusted HR 6.25 vs. 2.85; p-interaction 0.001) as well as in those with hemoglobin nadir > 9.0 g/dl (HR 4.01; p-interaction<0.0001).
Conclusion
In patients with NSTEMI, blood transfusion was associated with an overall increased risk of ischaemic events. However, this was mainly driven by patients without overt bleeding and those hemoglobin nadir > 9.0g/dl. This suggests possible harm of transfusion in those groups.

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

Int J Cardiol: 31 Oct 2020; 318:7-13
Deharo P, Ducrocq G, Bode C, Cohen M, ... Elbez Y, Steg PG
Int J Cardiol: 31 Oct 2020; 318:7-13 | PMID: 32590084
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Impact:
Abstract

Better adherence with out-of-hospital healthcare improved long-term prognosis of acute coronary syndromes: Evidence from an Italian real-world investigation.

Rea F, Ronco R, Pedretti RFE, Merlino L, Corrao G
Background
Patients who experience a hospital admission for acute coronary syndromes (ACS) exhibit poor prognosis over the years. The purposes of this study were to evaluate the real-world patterns of out-of-hospital practice in the management of ACS patients and to assess their impact on the risk of selected outcomes.
Methods
The cohort of 87,530 residents in the Lombardy Region (Italy) who were newly hospitalised for ACS during 2011-2015 was followed until 2018. Exposure to medical treatment including use of selected drugs, diagnostic procedures and laboratory tests was recorded. The main outcome of interest was re-hospitalisation for cardiovascular (CV) outcomes. Proportional hazards models were fitted to estimate hazard ratio, and 95% confidence intervals (CI), for the exposure-outcome association. Analyses were stratified according to the ACS type.
Results
The cumulative incidence of re-hospitalisation for CV disease was 33%, 42% and 38% at 5 years after index discharge among STEMI, NSTEMI and unstable angina patients. Within one year from index discharge, between 70% and 80% of patients had at least a prescription of statins, beta-blockers and renin-angiotensin-system blocking agents, underwent ECG and lipid profile examination, and had a cardiologic examination. One patient in five underwent cardiac rehabilitation. Compared with patients who did not adhere to healthcare recommendations, the risk of CV hospital readmission was reduced from 10% (95% CI: 4%-10%) to 23% (12%-32%) among patients who underwent lipid profile examinations and who experienced cardiac rehabilitation.
Conclusion
Close out-of-hospital healthcare must be considered the cornerstone for improving the long-term prognosis of ACS patients.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 31 Oct 2020; 318:14-20
Rea F, Ronco R, Pedretti RFE, Merlino L, Corrao G
Int J Cardiol: 31 Oct 2020; 318:14-20 | PMID: 32593725
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Impact:
Abstract

Neighborhood socioeconomic status and aortic stenosis: A Swedish study based on nationwide registries and an echocardiographic screening cohort.

Andell P, Li X, Martinsson A, Nilsson PM, ... Smith JG, Sundquist K
Background
Aortic stenosis (AS) is the most common valvular heart disease in developed countries, confers high mortality in advanced cases, but can effectively be reversed using endovascular or open-heart surgery. We evaluated the association between AS and neighborhood socioeconomic status (NSES).
Methods
We used Swedish population-based nationwide registers and an echocardiography screening cohort during the study period 1997-2014. NSES was determined by an established neighborhood deprivation index composed of education, income, unemployment, and receipt of social welfare. Multilevel adjusted logistic regression models determined the association between NSES and incident AS (according to ICD-10 diagnostic codes).
Results
The study population of men and women (n=6,641,905) was divided into individuals living in high (n = 1,608,815 [24%]), moderate (n = 3,857,367 [58%]) and low (n = 1,175,723 [18%]) SES neighborhoods. There were 63,227 AS cases in total. Low NSES (versus high) was associated with a slightly increased risk of AS (OR 1.06 [95% CI 1.03-1.08]) in the nationwide study population. In the echocardiography screening cohort (n = 1586), the association between low NSES and AS was markedly stronger (OR: 2.73 [1.05-7.12]). There were more previously undiagnosed AS cases in low compared to high SES neighborhoods (3.1% versus 1.0%).
Conclusions
In this nationwide Swedish register study, low NSES was associated with a slightly increased risk of incident AS. However, the association was markedly stronger in the echocardiography screening cohort, which revealed an almost three-fold increase of AS among individuals living in low SES neighborhoods, possibly indicating an underdiagnosis of AS among these individuals.

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

Int J Cardiol: 31 Oct 2020; 318:153-159
Andell P, Li X, Martinsson A, Nilsson PM, ... Smith JG, Sundquist K
Int J Cardiol: 31 Oct 2020; 318:153-159 | PMID: 32610152
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Impact:
Abstract

Long-term follow-up of patients with heart failure and reduced ejection receiving autonomic regulation therapy in the ANTHEM-HF pilot study.

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

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 06 Oct 2020; epub ahead of print
Sharma K, Premchand RK, Mittal S, Monteiro R, ... KenKnight BH, Anand IS
Int J Cardiol: 06 Oct 2020; epub ahead of print | PMID: 33038408
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Impact:
Abstract

Impact of renal function on the immediate and long-term outcomes of percutaneous recanalization of coronary chronic total occlusions: A systematic review and meta-analysis.

Moroni F, Spangaro A, Carlino M, Baber U, Brilakis ES, Azzalini L
Background
Renal impairment is associated with worse in-hospital and long-term outcomes after coronary artery revascularization, yet limited evidence is available on its impact on short- and long-term outcomes after chronic total occlusion (CTO) percutaneous coronary intervention (PCI).
Methods
We conducted a systematic review of the literature and subsequent random-effect meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) statement to evaluate the effect of chronic kidney disease (CKD), defined as estimated glomerular filtration rate < 60 ml/min/1.73 m, on CTO PCI. The outcomes of this study were in-hospital death, procedural failure, contrast-induced acute kidney injury and all-cause death at follow-up.
Results
Eight studies, with a total of 8439 patients (of whom 2256 had CKD) were included in the analysis. CKD was associated with higher technical (relative risk [RR] = 1.44, 95% confidence interval [CI] 1.14-1.82, p = .002) and procedural (risk ratio-RR = 1.40, 95% CI 1.00-1.96, p = .05) failure, higher in-hospital mortality (RR = 4.96, 95% CI 2.49-9.87 p < .001), bleeding complications (RR = 3.43, 95% CI 1.80-6.52, p < .001) and contrast-induced acute kidney injury (RR = 2.75, 95% CI 1.16-6.51, p = .001). CKD was also associated with higher all-cause mortality during long-term follow-up (RR = 3.56, 95% CI 1.08-5.99, p < .001).
Conclusion
Compared with patients with normal renal function, CKD is associated with lower success and higher risk of acute and long-term complications after CTO PCI. Kidney function should be considered during decision-making on CTO recanalization.

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

Int J Cardiol: 14 Oct 2020; 317:200-206
Moroni F, Spangaro A, Carlino M, Baber U, Brilakis ES, Azzalini L
Int J Cardiol: 14 Oct 2020; 317:200-206 | PMID: 32464250
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Impact:
Abstract

Coronary angiography and percutaneous coronary intervention after transcatheter aortic valve replacement with medtronic self-expanding prosthesis: Insights from correlations with computer tomography.

Khan M, Senguttuvan NB, Krishnamoorthy P, Vengrenyuk Y, ... Sharma SK, Kini A
Objectives
We aim to describe the feasibility, challenges, success rates and techniques utilized in coronary angiography (CA) and percutaneous coronary intervention (PCI) in patients post transcatheter aortic valve replacement (TAVR).
Background
CA and PCI after TAVR are becoming increasingly encountered in clinical practice. There have been technical difficulties reported in re-accessing the coronary arteries through the self-expanding CoreValve prosthesis.
Methods
From January 2012 to November 2017, 672 patients who underwent TAVR with a self-expanding prosthesis were retrospectively reviewed and those who had a CA and/or PCI post TAVR were analysed. Clinical characteristics, angiographic and procedural details were obtained. A subgroup of patients had computed tomographic angiography (CTA) post TAVR to evaluate positions of the coronary ostia relative to the self-expanding prosthesis. Study endpoint was successful selective engagement of coronary ostia for CA and PCI.
Results
Thirty-two patients (4.8%) had attempted 46 CA and 26 PCI after TAVR with a self-expanding valve. Mean age was 85.2 years and 41% were females. Selective left and right coronary angiography using standard catheters could be achieved in 50% and 28% of cases respectively. Successful PCI was performed in 25 cases (96%); however, significant technique modification was required in 64% of cases. CTA in 9 patients confirmed the difficulty in coronary re-access was due to a combination of the sealing skirt relationship to coronary ostia and sinotubular junction as well as commissural post orientation and significant native leaflet calcification.
Conclusions
CA and PCI post TAVR with self-expanding CoreValve is technically challenging but feasible with modification of standard techniques.

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

Int J Cardiol: 14 Oct 2020; 317:18-24
Khan M, Senguttuvan NB, Krishnamoorthy P, Vengrenyuk Y, ... Sharma SK, Kini A
Int J Cardiol: 14 Oct 2020; 317:18-24 | PMID: 32497567
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Impact:
Abstract

Safety of low intensity oral anticoagulant therapy in patients with bileaflet mechanical aortic valve prosthesis: A propensity weighted study.

Rubino AS, Torella M, Della Ratta EE, Galbiati D, ... De Santo LS, De Feo M
Background
Scarce data are available on the long-term outcomes of different regimens of oral anticoagulation in an all comer population of patients undergoing aortic valve replacement with a bileaflet mechanical heart valve.
Methods
Outcomes of 88 patients discharged with a target INR of 2.0 (LOW-INR) were compared to 147 contemporary patients who have been recommended a target INR of 2.5 (CONV). Primary outcome was the composite of any thromboembolic or haemorrhagic events. Secondary outcomes were the individual components of the primary outcome, cardiovascular mortality and stroke. To reduce selection bias, a propensity weighted analysis was performed.
Results
After inverse probability of treatment weighting, the primary endpoint occurred in 0.7% of patient in the LOW-INR group and in 7.0% in the CONV group (p = .0255). Linearized event rate were significantly lower in the LOW-INR group (primary endpoint: rate difference - 12.0 per 1000 patient/years, p = .0052; haemorrhage: -5.8 per 1000 patient/years, p = .0330; neurological events: -7.6 per 1000 patient/years, p = .0140). Conventional target INR was associated with an increased hazard of the composite endpoint (HR 11.193, 95% CI 1.424-88.003, p = .0217).
Conclusions
Lowering the intensity of oral anticoagulation resulted in a relevant clinical benefit of reduced rates of haemorrhagic and neurological adverse events in the mid-term follow-up. This report confirms the safety profile of the low INR regimen in an all comer population undergoing aortic valve replacement with an Abbott mechanical valve.

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

Int J Cardiol: 14 Oct 2020; 317:139-143
Rubino AS, Torella M, Della Ratta EE, Galbiati D, ... De Santo LS, De Feo M
Int J Cardiol: 14 Oct 2020; 317:139-143 | PMID: 32512061
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Abstract

Early detection of ST-segment elevated myocardial infarction by artificial intelligence with 12-lead electrocardiogram.

Zhao Y, Xiong J, Hou Y, Zhu M, ... Zhang Y, Xu Y

Patient delay is a worldwide unsolved problem in ST-segment elevated myocardial infarction (STEMI). An accurate warning system based on electrocardiogram (ECG) may be a solution for this problem, and artificial intelligence (AI) may offer a path to improve its accuracy and efficiency. In the present study, an AI-based STEMI autodiagnosis algorithm was developed using a dataset of 667 STEMI ECGs and 7571 control ECGs. The algorithm for detecting STEMI proposed in the present study achieved an area under the receiver operating curve (AUC) of 0.9954 (95% CI, 0.9885 to 1) with sensitivity (recall), specificity, accuracy, precision and F1 scores of 96.75%, 99.20%, 99.01%, 90.86% and 0.9372 respectively, in the external evaluation. In a comparative test with cardiologists, the algorithm had an AUC of 0.9740 (95% CI, 0.9419 to 1), and its sensitivity (recall), specificity, accuracy, precision, and F1 score were 90%, 98% and 94%, 97.82% and 0.9375 respectively, while the medical doctors had sensitivity (recall), specificity, accuracy, precision and F1 score of 71.73%, 89.33%, 80.53%, 87.05% and 0.8817 respectively. This study developed an AI-based, cardiologist-level algorithm for identifying STEMI.

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

Int J Cardiol: 14 Oct 2020; 317:223-230
Zhao Y, Xiong J, Hou Y, Zhu M, ... Zhang Y, Xu Y
Int J Cardiol: 14 Oct 2020; 317:223-230 | PMID: 32376417
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Abstract

Short-term regulation of hematopoiesis by lipoprotein(a) results in the production of pro-inflammatory monocytes.

Schnitzler JG, Poels K, Stiekema LCA, Yeang C, ... Lutgens E, Seijkens TTP
Background
Lipoproteins are important regulators of hematopoietic stem and progenitor cell (HSPC) biology, predominantly affecting myelopoiesis. Since myeloid cells, including monocytes and macrophages, promote the inflammatory response that propagates atherosclerosis, it is of interest whether the atherogenic low-density lipoprotein (LDL)-like particle lipoprotein(a) [Lp(a)] contributes to atherogenesis via stimulating myelopoiesis.
Methods & results
To assess the effects of Lp(a)-priming on long-term HSPC behavior we transplanted BM of Lp(a) transgenic mice, that had been exposed to elevated levels of Lp(a), into lethally-irradiated C57Bl6 mice and hematopoietic reconstitution was analyzed. No differences in HSPC populations or circulating myeloid cells were detected ten weeks after transplantation. Likewise, in vitro stimulation of C57Bl6 BM cells for 24 h with Lp(a) did not affect colony formation, total cell numbers or myeloid populations 7 days later. To assess the effects of elevated levels of Lp(a) on myelopoiesis, C57Bl6 bone marrow (BM) cells were stimulated with lp(a) for 24 h, and a marked increase in granulocyte-monocyte progenitors, pro-inflammatory Ly6 monocytes and macrophages was observed. Seven days of continuous exposure to Lp(a) increased colony formation and enhanced the formation of pro-inflammatory monocytes and macrophages. Antibody-mediated neutralization of oxidized phospholipids abolished the Lp(a)-induced effects on myelopoiesis.
Conclusion
Lp(a) enhances the production of inflammatory monocytes at the bone marrow level but does not induce cell-intrinsic long-term priming of HSPCs. Given the short-term and direct nature of this effect, we postulate that Lp(a)-lowering treatment has the capacity to rapidly revert this multi-level inflammatory response.

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

Int J Cardiol: 14 Sep 2020; 315:81-85
Schnitzler JG, Poels K, Stiekema LCA, Yeang C, ... Lutgens E, Seijkens TTP
Int J Cardiol: 14 Sep 2020; 315:81-85 | PMID: 32387421
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Abstract

Measuring atrial stasis during sinus rhythm in patients with paroxysmal atrial fibrillation using 4 Dimensional flow imaging: 4D flow imaging of atrial stasis.

Costello BT, Voskoboinik A, Qadri AM, Rudman M, ... Kistler PM, Taylor AJ
Background
Paroxysmal atrial fibrillation (PAF) is associated with cardioembolic risk, however events may occur during sinus rhythm (SR). 4D-flow cardiac magnetic resonance (CMR) imaging allows visualisation of left atrial blood flow, to determine the residence time distribution (RTD), an assessment of atrial transit time.
Objective
To determine if atrial transit time is prolonged in PAF patients during SR, consistent with underlying atrial stasis.
Method
91 participants with PAF and 18 healthy volunteers underwent 4D flow analysis in SR. Velocity fields were produced RTDs, calculated by seeding virtual \'particles\' at the right upper pulmonary vein and counting them exiting the mitral valve. An exponential decay curve quantified residence time of particles in the left atrium, and atrial stasis was expressed as the derived constant (RTD) based on heartbeats. The RTD was evaluated within the PAF group, and compared to healthy volunteers.
Results
Patients with PAF (n = 91) had higher RTD compared with gender-matched controls (n = 18) consistent with greater atrial stasis (1.68 ± 0.46 beats vs 1.51 ± 0.20 beats; p = .005). PAF patients with greater thromboembolic risk had greater atrial stasis (median RTD of 1.72 beats in CHA₂DS₂-VASc≥2 vs 1.52 beats in CHA₂DS₂-VASc<2; p = .03), only female gender and left ventricular ejection fraction contributed significantly to the atrial RTD (p = .006 and p = .023 respectively).
Conclusions
Atrial stasis quantified by 4D flow is greater in PAF, correlating with higher CHA₂DS₂-VASc scores. Female gender and systolic dysfunction are associated with atrial stasis. RTD offers an insight into atrial flow that may be developed to provide a personalised assessment of thromboembolic risk.

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

Int J Cardiol: 14 Sep 2020; 315:45-50
Costello BT, Voskoboinik A, Qadri AM, Rudman M, ... Kistler PM, Taylor AJ
Int J Cardiol: 14 Sep 2020; 315:45-50 | PMID: 32439367
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Abstract

Five-year mortality and readmission rates in patients with heart failure in India: Results from the Trivandrum heart failure registry.

Harikrishnan S, Jeemon P, Ganapathi S, Agarwal A, ... Suresh K, Huffman MD
Introduction
Heart failure (HF) has emerged as an important and increasing disease burden in India. We present the 5-year outcomes of patients hospitalized for HF in India.
Methods
The Trivandrum Heart Failure Registry (THFR) recruited consecutive patients admitted for acute HF among 16 hospitals in Trivandrum, Kerala in 2013. Guideline-directed medical therapy (GDMT) was defined as the combination of beta-blockers (BB), renin angiotensin system blockers (RAS), and mineralocorticoid receptor antagonists (MRA) in patients with HF with reduced ejection fraction (HFrEF, EF < 40%) at discharge. We used Cox proportional hazards models and Kaplan-Meier survival plots for analysis. The MAGGIC risk score variables were included as exposure variables.
Results
Among 1205 patients [69% male, mean (SD) age = 61.2 (13.7) years], HFrEF constituted 62% of patients and among them, 25% received GDMT. The 5-year mortality rate was 59% (n = 709 deaths), and median survival was 3.1 years. Sudden cardiac death and pump failure caused 46% and 49% of the deaths, respectively. In the multivariate Cox model, components of GDMT associated with lower 5-year mortality risks were discharge prescription of BB, RAS blocker, and MRA. Readmissions, older age, lower systolic blood pressure, NYHA class III or IV, and higher serum creatinine were also associated with higher 5-year mortality.
Conclusions
Three out of every 5 patients had died during 5-years of follow-up with a median survival of approximately 3 years. Lack of GDMT in patients with HFrEF and frequent readmissions were associated with higher 5-year mortality. Quality improvement programmes with strategies to improve adherence to GDMT and reduction in readmissions may improve HF outcomes in this region.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 09 Oct 2020; epub ahead of print
Harikrishnan S, Jeemon P, Ganapathi S, Agarwal A, ... Suresh K, Huffman MD
Int J Cardiol: 09 Oct 2020; epub ahead of print | PMID: 33049297
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Abstract

Obesity paradox in Korean male and female patients with heart failure: A report from the Korean heart failure registry.

Lee SY, Kim HL, Kim MA, Park JJ, ... Cho MC,
Background
Although the survival benefit of obesity has been suggested in patients with heart failure (HF), the impact of sex on obesity paradox is less clear. This study was performed to investigate whether there is a sex difference in the association between body mass index (BMI) and long-term clinical outcomes in patients hospitalized for HF.
Method
A total of 2616 patients hospitalized for HF (Mean age 66 years and 52% males) from the nation-wide registry database were analyzed. Patients were categorized using baseline BMI as normal (18.5 to 22.9 kg/m), overweight (23 to 27.4 kg/m) and obese (≥27.5 kg/m). Their all-cause mortality and long-term composite events, including all-cause mortality and HF readmission, were assessed according to the BMI groups.
Results
During the median follow-up period of 1499 days, there were 662 patients (25.3%) with all-cause mortality and 1071 patients (40.9%) with composite events. Compared to the normal weight group, the overweight (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.51-0.99; P = 0.045) and obese (HR, 0.53; 95% CI, 0.29-0.95; P = 0.032) group showed lower all-cause mortality rates even after adjusting for confounding factors in the male patients. Otherwise, BMI was not associated with composite events in males; it was not associated with all-cause mortality or composite events in females in the multivariable analyses (P > 0.05 for each).
Conclusions
Among patients with HF, a greater BMI was associated with low all-cause mortality in males, but not in females. Obesity paradox should be considered in the management of HF patients.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 08 Oct 2020; epub ahead of print
Lee SY, Kim HL, Kim MA, Park JJ, ... Cho MC,
Int J Cardiol: 08 Oct 2020; epub ahead of print | PMID: 33045277
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Abstract

Impact of intravascular ultrasound findings in patients with a post PCI fractional flow reserve ≤0.85 on 2 year clinical outcome.

van Zandvoort LJC, Masdjedi K, Neleman T, Tovar Forero MN, ... Van Mieghem NM, Daemen J
Background
Patients with a low post PCI fractional flow reserve (FFR) are at increased risk for future adverse cardiac events. The aim of the present study was to assess the impact of specific intravascular ultrasound (IVUS) findings in patients with a low post percutaneous coronary intervention (PCI) FFR on long-term clinical outcome.
Methods
In a subgroup analysis, 100 vessels with an FFR value ≤0.85 underwent post PCI IVUS to further assess the potential determinants for low post PCI FFR. No further action was taken to improve post PCI FFR. The primary endpoint of this study was the event free survival of target vessel failure (TVF) at two years in patients with a post PCI FFR ≤0.85, which was defined as a composite of cardiac death, target vessel myocardial infarction or target vessel revascularization.
Results
In patients with a post PCI FFR ≤0.85, TVF free survival rates were 88.5% vs. 95.5% for patients with versus without residual proximal lesions and 88.2% vs. 95.5% for patients with versus without residual distal lesions respectively (HR = 2.53, 95% confidence interval (CI) 0.52-12.25, p = .25 and HR = 2.60, 95% CI 0.54-12.59, p = .24 respectively). TVF free survival was 92.8% vs. 93.5% in patients with versus without stent underexpansion >20% (HR = 1.01, 95% CI 0.21-4.88, p = .99) and 89.3% vs. 97.8% in patients with versus without any residual focal lesion including lumen compromising hematoma (HR = 4.64, 95% CI 0.55-39.22, p = .18).
Conclusion
Numerically higher TVF rates were observed in patients with a post PCI FFR ≤0.85 and clear focal residual disease as assessed with IVUS.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Oct 2020; 317:33-36
van Zandvoort LJC, Masdjedi K, Neleman T, Tovar Forero MN, ... Van Mieghem NM, Daemen J
Int J Cardiol: 14 Oct 2020; 317:33-36 | PMID: 32433997
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Abstract

Identification of KIAA0196 as a novel susceptibility gene for myofibril structural disorganization in cardiac development.

Bu H, Yang Y, Wu Q, Tan Z, ... Hu S, Zhao T
Background
Congenital heart disease is one of the most common cardiac malformation-related diseases worldwide. Some causative genes have been identified but can explain only a small proportion of all cases; therefore, the discovery of novel susceptibility genes and/or modifier genes for abnormal cardiac development remains a major challenge.
Methods
We used a single nucleotide polymorphism (SNP) array, and next-generation sequencing (NGS) was conducted to screen and quickly identify candidate genes. KIAA0196 knockout zebrafish and mice were generated by CRISPR/Cas9 to detect whether or how KIAA0196 deficiency would influence cardiac development.
Results
Homozygous, but not heterozygous, zebrafish and mice showed early embryonic lethality. At the embryonic stage, microscopic examination and dissection revealed pericardial edema and ventricle enlargement in homozygous zebrafish and obviously delayed cardiac development in heterozygous mice, while echocardiography and tissue staining showed that significantly decreased cardiac function, ventricle enlargement, myofibril loss, and significantly reduced trabecular muscle density were observed in adult heterozygous zebrafish and mice. Most importantly, immunostaining and electron microscopy showed that there was a significant increase in sarcomere structural disorganization and myofibril structural integrity loss in KIAA0196 mutants. Furthermore, substantial downregulation in other sarcomeric genes and proteins was detected and verified in a mouse model via transcriptome and proteomics analyses; these changes especially affected the myosin heavy or light chain (MYH or MYL) family genes.
Conclusion
We identified KIAA0196 for the first time as a susceptibility gene for abnormal cardiac development. KIAA0196 deficiency may cause abnormal heart development by influencing the structural integrity of myofibrils.

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

Int J Cardiol: 31 Aug 2020; 314:81-88
Bu H, Yang Y, Wu Q, Tan Z, ... Hu S, Zhao T
Int J Cardiol: 31 Aug 2020; 314:81-88 | PMID: 32417190
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Abstract

The value of extensive catheter linear ablation on persistent atrial fibrillation (the CLEAR-AF Study).

Yao Y, Hu F, Du Z, He J, ... Liang E, Wu L
Background
The ablation therapy for persistent atrial fibrillation (PerAF) is still a challenge due to the high recurrence rate. This study was aimed to investigate the value of extensive linear ablation with contact force sensing techniques for PerAF.
Methods
A total of 214 patients with PerAF were enrolled in five centers. The patients were randomly assigned to Group I (PVI + LA roof line+ LA anterior wall line) and Group II (PVI + LA roof line), mitral valve isthmus lines were added in both groups if the atrial fibrillation (AF) could not be terminated after all approaches above.
Results
Acute success rate of AF termination during the ablation procedure in Group I was significantly higher than Group II (P = 0.028). Two-years follow-up showed no significant difference in the sinus rhythm maintenance rate between the two groups (63.4% in group I vs. 57.2% in group II, P = 0.218). More patients in Group I recurred as organized atrial tachycardia (AT) and can be precisely mapped during repeat ablation procedures (15 vs. 2, P = 0.001). The Kaplan-Meier estimates of AF/AT-free survival after repeat ablation procedures were 76.2% in Group I and 47.1% in Group II (P = 0.039).
Conclusions
Extensive linear ablation with contact force monitoring did not improve the long-term outcomes for PerAF patients. Repeat ablation procedure showed a possible higher chance of sinus rhythm restoration during follow-up.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 30 Sep 2020; 316:125-129
Yao Y, Hu F, Du Z, He J, ... Liang E, Wu L
Int J Cardiol: 30 Sep 2020; 316:125-129 | PMID: 32461117
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Abstract

High incidence of subclinical atrial fibrillation in patients with syncope monitored with implantable cardiac monitor.

Francisco-Pascual J, Olivella San Emeterio A, Rivas-Gándara N, Pérez-Rodón J, ... Cantalapiedra Romero J, Ferreira González I
Objective
The use of implantable cardiac monitors (ICM) is highly useful in syncope workup. Latest-generation devices can detect asymptomatic episodes of atrial fibrillation. The main objective of this study was to determine the incidence of subclinical atrial fibrillation (AF) detected in a patient population undergoing prolonged electrocardiographic monitoring with an ICM for the etiological workup of syncope.
Methods
Prospective observational study carried out in a tertiary hospital from April 2014 to October 2019. All consecutive adult patients monitored with a latest-generation ICM for syncope with no prior history of AF were included in the analysis.
Results
Of a total of 509 ICMs implanted during the study period, 208 patients fulfilled the inclusion criteria. 42 patients (20.2%) were found to have AF on ICM. The incidence of AF was 11.7 cases per 100 person-years (95% CI: 8.7-15.9 per 100 person-years). The median burden of AF was 0.2% (IQR 0-0.8%). Age, the presence of hypertension, chronic kidney disease, the size of the septum and left atrium on electrocardiogram and the presence of broad QRS on baseline electrocardiogram were predictors for the appearance of AF in the univariate analysis.
Conclusion
The incidental finding of atrial fibrillation in patients with syncope monitored with ICM is common. The burden of AF is low, and it is generally subclinical. These findings create added value for the use of ICM in the workup for syncope, although further studies are needed to determine the clinical benefit of documenting subclinical AF.

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

Int J Cardiol: 30 Sep 2020; 316:110-116
Francisco-Pascual J, Olivella San Emeterio A, Rivas-Gándara N, Pérez-Rodón J, ... Cantalapiedra Romero J, Ferreira González I
Int J Cardiol: 30 Sep 2020; 316:110-116 | PMID: 32470530
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Abstract

Endothelial progenitor cells predict long-term outcome in patients with coronary artery disease: Ten-year follow-up of the PROCREATION extended study.

Pelliccia F, Pasceri V, Moretti A, Tanzilli G, Speciale G, Gaudio C
Background
Levels of circulating endothelial progenitor cells (EPCs) are associated with the short-term prognosis of patients with coronary artery disease (CAD). No previous study, however, has ascertained if EPCs are related also to long-term outcome. We performed a pre-specified analysis of the PROCREATION (PROgenitor Cells role in Restenosis and progression of coronary ATherosclerosis after percutaneous coronary intervention) study in order to assess if EPCs predict the 10-year prognosis.
Methods and results
Consecutive stable patients with CAD who were included in the PROCREATION study were evaluated. Patients underwent an extended 10-year follow-up to assess major adverse cardiac or cerebrovascular events (MACCE), i.e. death, stroke, myocardial infarction, and revascularization. During follow-up, MACCE occurred in 79 of 149 patients (53%). Most clinical and angiographic baseline variables were similar in patients with or without MACCE, apart from age, diabetes, chronic kidney disease, ejection fraction, and extent of CAD. Comparison of EPCs, conversely, showed that patients with MACCE had greater levels of CD34+/KDR+/CD45- cells (p=0.0002) and CD133+/KDR+/CD45- cells (p=0.0001). Multivariate analysis showed that factors independently associated with 10-year MACCEs were age (p=0.001), ejection fraction (p=0.018), and CD34+/KDR+/CD45- cells (p=0.024).
Conclusion
Subpopulations of EPCs can improve long-term risk factor characterization in patients with CAD. (ClinicalTrials.gov: NCT01575431).

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 31 Oct 2020; 318:123-125
Pelliccia F, Pasceri V, Moretti A, Tanzilli G, Speciale G, Gaudio C
Int J Cardiol: 31 Oct 2020; 318:123-125 | PMID: 32522679
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Abstract

Pulmonary vein isolation with the cryoballoon in obese atrial fibrillation patients - Does weight have an impact on procedural parameters and clinical outcome?

Weinmann K, Bothner C, Rattka M, Aktolga D, ... Dahme T, Pott A
Introduction
Obesity is a known risk factor for the incidence and prevalence of atrial fibrillation (AF). Pulmonary vein isolation (PVI) is an established therapeutic option for AF patients, however clinical benefit of AF ablation remains controversial in overweight and obese patients. We investigated the impact of overweight and obesity in AF patients undergoing cryoballoon PVI on procedural characteristics and clinical outcome.
Methods
We included consecutive patients undergoing cryoballoon PVI at Ulm University Medical center. Normal weight was defined as a body mass index (BMI) of 18.5-24.9 kg/m, overweight as a BMI of 25.0-29.9 kg/m and obesity as a BMI of ≥30.0 kg/m.
Results
Evaluating 600 patients, mean age was 66.3±10.8 years and 43% patients were female. 41% of the patients were classified as overweight and 34% as obese. Regarding procedural characteristics, overweight and obese patients had longer fluoroscopy area dose product (p<0.001) and obese patients a higher fluoroscopy time (p<0.05). Analyses of ablation related procedural characteristics revealed no relevant differences regarding number and duration of ablation, time to isolation and nadir temperature. Importantly, recurrence of atrial arrhythmia was statistically not different comparing normal weight, overweight and obese patients.
Conclusion
Besides higher radiation exposure, cryoballoon PVI in overweight and obese patients is as safe and efficient as in normal weight patients. It is reasonable to proceed with cryoballoon PVI on overweight and obese patients as would be done in normal weight patients, since this might encourage overweight and obese patients to exercise.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 30 Sep 2020; 316:137-142
Weinmann K, Bothner C, Rattka M, Aktolga D, ... Dahme T, Pott A
Int J Cardiol: 30 Sep 2020; 316:137-142 | PMID: 32522675
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Abstract

The effects of combination canagliflozin and glucagon-like peptide-1 receptor agonist therapy on intermediate markers of cardiovascular risk in the CANVAS program.

Arnott C, Neuen BL, Heerspink HJL, Figtree GA, ... Perkovic V, Neal B
Background
Sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) reduce cardiovascular events, and improve intermediate markers of cardiometabolic health, in those with type 2 diabetes. We investigated these effects in the CANVAS Program.
Methods and results
The CANVAS Program comprised 2 double-blind, randomized, placebo-controlled trials (CANVAS and CANVAS-R) done in patients with type 2 diabetes and elevated cardiovascular risk. Effects were estimated using mixed-effects models for continuous measures and Cox regression models for other outcomes. Randomized treatment by subgroup interaction terms were used to compare effects of canagliflozin versus placebo across subgroups defined by baseline use of GLP1-RA. There were 10,142 participants, of whom 407 (4%) were using GLP1-RA therapy at baseline. Those using GLP1-RA at baseline were less likely to have a history of cardiovascular disease (60.4% vs 65.8%), had a longer duration of diabetes (15.2 vs 13.5 years) and a higher body mass index (BMI; 35.6 vs 31.8 kg/m) but were otherwise similar. There were greater reductions with canagliflozin versus placebo for HbA1c (-0.75% versus -0.58%; P = .0091), SBP (-6.26 versus -3.83 mmHg; P = .0018), and body weight (-3.79 versus -2.18 kg; P < .0001) in those on baseline GLP1-RA therapy. Effects across subgroups were similar for UACR (P = .21), eGFR slope (P = .72), major adverse cardiac events (P = .94) and total serious adverse events (P = .74).
Conclusions
There may be a synergistic effect of SGLT2 inhibition when used on a background of GLP1-RA for intermediate cardiometabolic markers.

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

Int J Cardiol: 31 Oct 2020; 318:126-129
Arnott C, Neuen BL, Heerspink HJL, Figtree GA, ... Perkovic V, Neal B
Int J Cardiol: 31 Oct 2020; 318:126-129 | PMID: 32569700
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Abstract

Association between cardioplegia and postoperative atrial fibrillation in coronary surgery.

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

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

Int J Cardiol: 03 Oct 2020; epub ahead of print
Mauro MD, Calafiore AM, Di Franco A, Nicolini F, ... Gaudino M, Lorusso R
Int J Cardiol: 03 Oct 2020; epub ahead of print | PMID: 33022288
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Impact:
Abstract

Two-year outcomes post-discharge in Asian patients with acute coronary syndrome: Findings from the EPICOR Asia study.

Huo Y, Lee SW, Sawhney JPS, Kim HS, ... Hayashi N, Ong TK
Aims
Approximately half of cases of cardiovascular disease (CVD) worldwide occur in Asia, with acute coronary syndrome (ACS) a leading cause of mortality. Long-term ACS-related outcomes data in Asia are limited. This analysis examined 2-year ACS-related outcomes in patients enrolled in the EPICOR Asia study, and the association between patient characteristics and management on outcomes.
Methods
EPICOR Asia is a multinational, prospective, primary data collection study of real-world management of Asian patients with ACS. Overall, 12,922 eligible adults (hospitalized for ACS within 48 h of symptom onset and who survived to discharge) were enrolled from 219 centers in eight Asian countries. Patients were followed up post-discharge for 2 years and clinical outcomes recorded.
Results
Patients were of mean age 60 years and 76% were male. Diagnoses were STEMI (51.2%), NSTEMI (19.9%), and UA (28.9%). During follow-up, 5.2% of patients died; NSTEMI patients had the highest risk profile. Mortality rate (adjusted HR [95% CI]) was similar in NSTEMI (0.97 [0.81-1.17]) and lower in UA (0.52 [0.33-0.82]) vs STEMI. Similar trends (adjusted) were seen for the composite endpoint of death, myocardial infarction, or ischemic stroke, and bleeding rates did not differ significantly. For all three diagnoses, patients who were medically managed had a markedly elevated risk of both death and the composite endpoint.
Conclusions
During 2-year follow-up, adjusted risks of mortality, the composite endpoint, and bleeding rates were similar in NSTEMI and STEMI patients. Outcomes risk was better for invasive management. Long-term management strategies in Asia need to be optimized.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 14 Sep 2020; 315:1-8
Huo Y, Lee SW, Sawhney JPS, Kim HS, ... Hayashi N, Ong TK
Int J Cardiol: 14 Sep 2020; 315:1-8 | PMID: 32389764
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Impact:
Abstract

External validation of existing prediction models of 30-day mortality after Transcatheter Aortic Valve Implantation (TAVI) in the Netherlands Heart Registration.

Al-Farra H, Abu-Hanna A, de Mol BAJM, Ter Burg WJ, ... Ravelli ACJ,
Background
Several mortality prediction models (MPM) are used for predicting early (30-day) mortality following transcatheter aortic valve implantation (TAVI). Little is known about their predictive performance in external TAVI populations. We aim to externally validate established MPMs on a large TAVI dataset from the Netherlands Heart Registration (NHR).
Methods
We included data from NHR-patients who underwent TAVI during 2013-2017. We calculated the predicted mortalities per MPM. We assessed the predictive performance by discrimination (Area Under Receiver Operating-characteristic Curve, AU-ROC); the Area Under Precision-Recall Curve, AU-PRC; calibration (using calibration-intercept and calibration-slope); Brier Score and Brier Skill Score. We also assessed the predictive performance among subgroups: tertiles of mortality-risk for non-survivors, gender, and access-route.
Results
We included 6177 TAVI-patients with an observed early-mortality rate of 4.5% (n = 280). We applied seven MPMs (STS, EuroSCORE-I, EuroSCORE-II, ACC-TAVI, FRANCE-2, OBSERVANT, and German-AV) on our cohort. The highest AU-ROCs were 0.64 (95%CI 0.61-0.67) for ACC-TAVI and 0.63 (95%CI 0.60-0.67) for FRANCE-2. All MPMs had a very low AU-PRC of ≤0.09. ACC-TAVI had the best calibration-intercept and calibration-slope. Brier Score values ranged between 0.043 and 0.063. Brier Skill Score ranged between -0.47 and 0.004. ACC-TAVI and FRANCE-2 predicted high mortality-risk better than other MPMs. ACC-TAVI outperformed other MPMs in different subgroups.
Conclusion
The ACC-TAVI model has relatively the best predictive performance. However, all models have poor predictive performance. Because of the poor discrimination, miscalibration and limited accuracy of the models there is a need to update the existing models or develop new TAVI-specific models for local populations.

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

Int J Cardiol: 14 Oct 2020; 317:25-32
Al-Farra H, Abu-Hanna A, de Mol BAJM, Ter Burg WJ, ... Ravelli ACJ,
Int J Cardiol: 14 Oct 2020; 317:25-32 | PMID: 32450275
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Impact:
Abstract

Supra-annular sizing of transcatheter aortic valve prostheses in raphe-type bicuspid aortic valve disease: the LIRA method.

Iannopollo G, Romano V, Buzzatti N, Ancona M, ... Chieffo A, Montorfano M
Background
Recent evidence shows that THV prostheses anchoring occurs at the raphe-level, known as LIRA plane, in raphe-type bicuspid aortic valve (BAV) disease. The purpose of this study was to evaluate the application of a novel supra-annular sizing method, known as Level of Implantation at the RAphe (LIRA) method, to optimize transcatheter heart valve (THV) prosthesis sizing in raphe-type BAV disease.
Methods and results
The LIRA method was applied to all consecutive patients with raphe-type BAV disease between November 2018 to January 2020 in our centre. THV prostheses were sized on the basis of baseline CT scan perimeters at the LIRA plane and at the virtual basal ring. In case of discrepancy between the two plane measurements, the plane with the smallest perimeter was considered the reference for prosthesis sizing. Post-procedural device success, defined according to Valve Academic Research Consortium-2 (VARC-2) criteria, was evaluated in the overall cohort. 20 patients (mean patient age 81 ± 5.4 years, 70% males) were identified as having a raphe-type BAV disease at pre-procedural CT scans and were implanted with different types of THV prostheses. The LIRA plane method appeared to be highly successful (100% VARC-2 device success) with no procedural mortality, no valve migration, no moderate-severe paravalvular leak and low transprosthetic gradient (residual mean gradient of 8.2 ± 2.9 mm Hg).
Conclusions
Supra-annular sizing according to the LIRA method appeared to be safe with a high device success. The application of the LIRA method might optimize THV prosthesis sizing in patients with raphe-type BAV disease.

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

Int J Cardiol: 14 Oct 2020; 317:144-151
Iannopollo G, Romano V, Buzzatti N, Ancona M, ... Chieffo A, Montorfano M
Int J Cardiol: 14 Oct 2020; 317:144-151 | PMID: 32473284
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Impact:
Abstract

Prognostic implications of pathogenic truncating variants in the TTN gene.

Peña-Peña ML, Ochoa JP, Barriales-Villa R, Cicerchia M, ... Monserrat L, Crespo-Leiro MG
Introduction and objectives
TTN gene truncating variants (TTNtv) are a frequent cause of dilated cardiomyopathy (DCM). However, there are discrepant data on the associated prognosis. Our objectives were to describe the prevalence of TTNtv in our cohort and to compare the clinical course with that described in the literature.
Methods
We included patients with DCM and genetic testing performed using next-generation sequencing. Through a systematic literature research, we collected information about carriers and affected relatives with TTNtv. We compared the cumulative percentage of affected carriers and the survival free of cardiovascular death.
Results
One hundred and ten DCM patients were evaluated. A total of 13 TTNtv distributed in 14 probands were identified (12.7%). We found a 21.4% prevalence in familial cases. No significant differences in the relation between age and clinical disease expression were identified. Survival free of cardiovascular death curves constructed from data in the literature seems not to overestimate the risk in our population.
Conclusions
The identification of TTNtv in patients with DCM is frequent and provides relevant information about the disease prognosis. The risk of cardiovascular death should not be underestimated. Age related penetrance need to be considered in the familial evaluation.

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

Int J Cardiol: 30 Sep 2020; 316:180-183
Peña-Peña ML, Ochoa JP, Barriales-Villa R, Cicerchia M, ... Monserrat L, Crespo-Leiro MG
Int J Cardiol: 30 Sep 2020; 316:180-183 | PMID: 32371228
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Impact:
Abstract

Estimating the health loss due to poor engagement with cardiac rehabilitation in Australia.

Driscoll A, Hinde S, Harrison A, Bojke L, Doherty P
Background
Cardiac rehabilitation (CR) programs are effective in reducing cardiovascular mortality and readmissions. However, most patients are denied the benefits of CR due to low referral rates. Of those patients referred, commencement rates vary from 28.4% to 60%. This paper quantifies the scale of health loss in Australia due to poor engagement with the program, and estimates how much public funding can be justifiably reallocated to address the problem.
Methods
Economic decision modelling was undertaken to estimate the expected lifetime health loss and costs to Medicare. Key parameters were derived from Australian databases, CR registries and meta-analyses. Population health gains associated with uptake rates of 60%, and 85% were calculated.
Results
CR was associated with a 99.9% probability of being cost-effective, even at a cost-effectiveness threshold lower than conventionally applied. Importantly, an average of 0.52 years of life expectancy are lost due to national uptake being below 60% achieved in some best performing programs in Australia, equivalent to 0.28 quality adjusted life years. The analysis indicates that $12.9 million/year could be justifiably reallocated from public funds to achieve a national uptake rate of 60%, while maintaining cost-effectiveness of CR due to the large health gains that would be expected.
Conclusion
CR is a cost-effective service for patients with coronary heart disease. In Australia, less than a third of patients commence CR, potentially resulting in avoidable patient harm. Additional investment in CR is vital and should be a national priority as the health gains for patients far outweigh the costs.

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

Int J Cardiol: 14 Oct 2020; 317:7-12
Driscoll A, Hinde S, Harrison A, Bojke L, Doherty P
Int J Cardiol: 14 Oct 2020; 317:7-12 | PMID: 32376418
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Abstract

Feasibility of intracoronary nicorandil for inducing hyperemia on fractional flow reserve measurement: Comparison with intracoronary papaverine.

Matsumoto H, Mikuri M, Masaki R, Tanaka H, ... Okada N, Shinke T
Background
Adenosine and adenosine triphosphate (ATP) are widely used to induce hyperemia for fractional flow reserve (FFR) measurements. Caffeine attenuates their hyperemic effects, but not those of nicorandil and papaverine. No studies have systematically compared the hyperemic efficacies of nicorandil, papaverine, and ATP with and without caffeine abstention.
Methods
FFRs were measured using nicorandil 2 mg (FFR), nicorandil 4 mg (FFR), and papaverine (FFR) in 40 patients (group 1), and using nicorandil 2 mg, ATP (FFR), ATP plus nicorandil (FFR), and papaverine in 20 patients with (group 2) and in 20 patients without caffeine abstention (group 3).
Results
In group 1, FFR and FFR did not differ (p = 0.321) and were higher than FFR (p < 0.001 and p = 0.0026). Likewise, FFR was higher than FFR in groups 2 (p = 0.049) and 3 (p < 0.010). In the whole group, Bland-Altman analysis showed a modest mean difference (0.015, p < 0.001) and narrow 95% limits of agreement (-0.025 and 0.056). FFR and FFR strongly correlated (r = 0.975, p < 0.001). Compared with FFR, FFR and FFR did not differ in group 2 (p = 1.0 and p = 0.780), but they were higher (p = 0.002 and p = 0.02) in group 3. Adjunctive nicorandil did not decline FFR further in groups 2 (p = 0.942) and 3 (p = 0.294).
Conclusions
Nicorandil 2 mg is a safe and practical alternative for patients who consume caffeine-containing products before the test or have contraindications for adenosine/ATP. Increasing the nicorandil dose to 4 mg or administering adjunctive nicorandil during ATP infusions does not offer any clinical advantages compared with administering nicorandil 2 mg alone.

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

Int J Cardiol: 31 Aug 2020; 314:1-6
Matsumoto H, Mikuri M, Masaki R, Tanaka H, ... Okada N, Shinke T
Int J Cardiol: 31 Aug 2020; 314:1-6 | PMID: 32387252
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Impact:
Abstract

Infarct size following loading with Ticagrelor/Prasugrel versus Clopidogrel in ST-segment elevation myocardial infarction.

Sabbah M, Nepper-Christensen L, Køber L, Høfsten DE, ... Lønborg J, Engstrøm T
Background
Treatment with newer direct-acting anti-platelet drugs (Ticagrelor and Prasugrel) prior to primary percutaneous coronary intervention (PCI) is associated with improved outcome in patients with ST-segment elevation myocardial infarction (STEMI) when compared with Clopidogrel. We compared infarct size following treatment with Ticagrelor/Prasugrel versus Clopidogrel in the DANish trial in Acute Myocardial Infarction (DANAMI-3) population of STEMI patients treated with primary PCI.
Methods and results
Patients were loaded with Clopidogrel, Ticagrelor or Prasugrel in the ambulance before primary PCI. Infarct size and myocardial salvage index were calculated using cardiac magnetic resonance (CMR) during index admission and at three-month follow-up. Six-hundred-and-ninety-three patients were included in this analysis. Clopidogrel was given to 351 patients and Ticagrelor/Prasugrel to 342 patients. The groups were generally comparable in terms of baseline and procedural characteristics. Median infarct size at three-month follow-up was 12.9% vs 10.0%, in patients treated with Clopidogrel and Ticagrelor/ Prasugrel respectively (p < 0.001), and myocardial salvage index was 66% vs 71% (p < 0.001). Results remained significant in a multiple regression model (p < 0.001).
Conclusions
Pre-hospital loading with Ticagrelor or Prasugrel compared to Clopidogrel, was associated with smaller infarct size and larger myocardial salvage index at three-month follow-up in patients with STEMI treated with primary PCI.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 31 Aug 2020; 314:7-12
Sabbah M, Nepper-Christensen L, Køber L, Høfsten DE, ... Lønborg J, Engstrøm T
Int J Cardiol: 31 Aug 2020; 314:7-12 | PMID: 32389767
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Impact:
Abstract

Progressive stiffening and relatively slow growth of the dilated ascending aorta in long-term Fontan survivors-Serial assessment for 15 years.

Hayama Y, Ohuchi H, Negishi J, Iwasa T, ... Tsuda E, Kurosaki K
Background
A stiffened, dilated ascending aorta may represent an important predictor of cardiovascular mortality, and has been reported in patients with congenital heart disease, including single ventricle. However, the serial conformational changes and determinants of reduced distensibility in ascending aorta have not been clarified.
Methods
This retrospective study investigated 115 postoperative Fontan survivors (median age at Fontan: 3.7 years). All patients underwent cardiac catheterization before and 1, 5, 10, and 15 years after the Fontan operation. We measured Z-scores for diameters and stiffness indexes (β) of the ascending aorta and descending aorta from angiograms. We also reviewed the clinical profiles, hemodynamic parameters, and exercise capacities of patients and compared them with results from 47 control subjects.
Results
Fontan survivors displayed significantly larger Z-score and β of the ascending aorta from before to 15 years after surgery than controls, whereas values for the descending aorta were comparable. Z-score for the ascending aorta was decreased, but β was elevated significantly according to the trend test. In multivariable analysis, β of the ascending aorta at 15 years after Fontan operation and its increasing trend were associated with older age at Fontan operation and elevated ventricular end-diastolic pressure. Reduced exercise capacity also correlated with stiffening of the ascending aorta.
Conclusions
Fontan survivors showed progressive stiffening and relatively slow growth of the dilated ascending aorta. Progressive stiffening of the ascending aorta may be coupled to diastolic dysfunction and reduced exercise capacity, suggesting the importance of lifelong management of subclinical Fontan pathophysiology.

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

Int J Cardiol: 30 Sep 2020; 316:87-93
Hayama Y, Ohuchi H, Negishi J, Iwasa T, ... Tsuda E, Kurosaki K
Int J Cardiol: 30 Sep 2020; 316:87-93 | PMID: 32389766
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Impact:
Abstract

Exacerbation of autoimmune myocarditis by an immune checkpoint inhibitor is dependent on its time of administration in mice.

Tsuruoka K, Wakabayashi S, Morihara H, Matsunaga N, ... Imagawa A, Asahi M
Background
Although immune checkpoint inhibitors (ICIs) have made an immense breakthrough in cancer therapeutics, they can exert unique, immune-related adverse events. Among them, myocarditis is less frequent, but it is serious and often follows a lethal course.
Methods
To examine the changes in cardiac autoimmunity after ICI administration, we developed a mouse experimental autoimmune myocarditis (EAM) model via intraperitoneal administration of murine α-cardiac myosin heavy chain (MyHC-α) fragment. Thereafter, the mouse anti-PD-1 antibody (mPD1ab) was administered at two time points, subsequent to and concurrent with MyHC-α fragment administration.
Results
Severe EAM developed in 3 weeks; wide inflammatory lesions were observed in the cardiac sections. Furthermore, inflammatory/fibrotic genes, such as interleukin 1β, interleukin 6, and collagen 1, were upregulated, although the cardiac function was not significantly affected. The subsequent administration of mPD1ab at 2 weeks post administration of the first MyHC-α fragment exacerbated EAM, whereas the administration of mPD1ab concurrent with MyHC-α fragment administration did not exacerbate EAM. The subsequent administration of mPD1ab significantly increased the infiltration of cluster of differentiation (CD)4- and F4/80-positive cells, whereas the concurrent administration of mPD1ab significantly decreased the infiltration of CD4-positive cells, indicating that the concurrent and subsequent administration of mPD1ab had opposite effects on immune/inflammatory cell infiltration.
Conclusions
These data suggest that the appearance of ICI-induced autoimmune myocarditis might be related to autoimmune system activity before ICI administration. Although ICIs do not adversely affect patients with normal immune systems, we propose that ICI administration should be avoided in patients with autoimmune disorders.

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

Int J Cardiol: 14 Aug 2020; 313:67-75
Tsuruoka K, Wakabayashi S, Morihara H, Matsunaga N, ... Imagawa A, Asahi M
Int J Cardiol: 14 Aug 2020; 313:67-75 | PMID: 32402518
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Impact:
Abstract

Contact feedback improves 1-year outcomes of remote magnetic navigation-guided ischemic ventricular tachycardia ablation.

Noten AME, Hendriks AA, Yap SC, Mol D, ... Khan M, Szili-Torok T
Introduction
Remote magnetic navigation (RMN)-guided catheter ablation (CA) is a feasible treatment option for patients presenting with ischemic ventricular tachycardia (VT). Catheter-tissue contact feedback, enhances lesion formation and may consequently improve CA outcomes. Until recently, contact feedback was unavailable for RMN-guided CA. The novel e-Contact Module (ECM) was developed to continuously monitor and ensure catheter-tissue contact during RMN-guided CA.
Objective
The present study aims to evaluate the effect of ECM implementation on acute and long-term outcomes in RMN-guided ischemic VT ablation.
Method
This retrospective, two-center study included consecutive ischemic VT patients undergoing RMN-guided CA from 2010 to 2017. Baseline clinical data, procedural data, including radiation times, and acute success rates were compared between CA procedures performed with ECM (ECM+) and without ECM (ECM-). One-year VT-free survival was analyzed using Cox-proportional hazards models, adjusting for potential confounders: age, left ventricular function, VT inducibility at baseline and substrate based ablation strategy.
Results
The current study included 145 patients (ECM+ N = 25, ECM- N = 120). Significantly lower fluoroscopy times were observed in the ECM+ group (9.5 (IQR 5.3-13.5) versus 12.5 min (IQR 8.0-18.0), P = 0.025). Non-inducibility of the clinical VT at the end of procedure was observed in 92% ECM+ versus 72% ECM- patients (P = 0.19). ECM guidance was associated with significantly lower VT-recurrence rates during 1-year follow-up (16% ECM+ versus 40% ECM-; multivariable HR 0.29, 95%-CI 0.10-0.69, P = 0.021, reference group: ECM-).
Conclusion
Contact feedback by the ECM further decreases fluoroscopy exposure and improves VT-free survival in RMN-guided ischemic VT ablation.

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

Int J Cardiol: 14 Sep 2020; 315:36-44
Noten AME, Hendriks AA, Yap SC, Mol D, ... Khan M, Szili-Torok T
Int J Cardiol: 14 Sep 2020; 315:36-44 | PMID: 32413467
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Impact:
Abstract

Blood haemoglobin, renal insufficiency, fractional flow reserve and plasma NT-proBNP is associated with index of microcirculatory resistance in chronic coronary syndrome.

Östlund-Papadogeorgos N, Ekenbäck C, Jokhaji F, Mir-Akbari H, ... Samad BA, Persson J
Background
Coronary microvascular dysfunction (CMVD) is associated with adverse cardiovascular outcome. We aimed to determine the prevalence of CMVD and factors related to index of microcirculatory resistance (IMR) in consecutive patients with chronic coronary syndrome (CCS) undergoing elective coronary angiography.
Methods and results
Non-interventional physicians enrolled 274 patients with CCS before angiography, to minimize selection bias by PCI-operators. Fractional flow reserve (FFR) and IMR were measured in the LAD. Subjects with extensively diseased LAD, no measures due to technical reasons or violation of protocol were excluded from the analysis (n = 54). The proportion of patients with IMR corrected for collateral flow (IMR) >25 units was 25% (95% confidence interval [CI] 19%-31%) in all 220 patients. In subjects with FFR ≤0.80 in the LAD the proportion of IMR > 25 units was 21% (95% CI 13%-30%) as compared to subjects with FFR >0.80, 29% (95% CI 21%-36%), p = .268. Haemoglobin (p < .005; r2 = 0.084), FFR in the LAD (p = .001; r2 = 0.049), creatinine clearance (p = .001; r = 0.049; inversely), and NT-proBNP (p = .038; r = 0.021) were independently associated with IMR in multivariate linear regression analysis.
Conclusions
We report that IMR is associated with renal dysfunction, NT-proBNP, FFR in the LAD and, for the first time, blood haemoglobin. One in four of patients referred for coronary angiography due to CCS have CMVD defined as IMR > 25 in the LAD.

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

Int J Cardiol: 14 Oct 2020; 317:1-6
Östlund-Papadogeorgos N, Ekenbäck C, Jokhaji F, Mir-Akbari H, ... Samad BA, Persson J
Int J Cardiol: 14 Oct 2020; 317:1-6 | PMID: 32464253
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Impact:
Abstract

Long-term variations of FFR and iFR after transcatheter aortic valve implantation.

Scarsini R, Lunardi M, Venturi G, Pighi M, ... Pesarini G, Ribichini F

Long-term variations of fractional flow reserve (FFR) and instantaneous wave-free-ratio (iFR) after transcatheter aortic valve implantation (TAVI) have not been previously assessed. A total of 23 coronary lesions in 14 patients with aortic stenosis (AS) underwent physiology assessment at baseline, immediately after TAVI and at 14(7-29) months of follow-up. The angiographic severity of the lesions did not progress at follow-up (54[45-64] vs 54[49-63], p = .53). Overall, FFR (0.87[0.85-0.92] vs 0.88[0.82-0.92], p = .45) and iFR (0.88[0.85-0.96] vs 0.91[0.86-0.97], p = .30) did not change significantly compared with the baseline. FFR decreased in 3(13%) lesions with abnormal baseline value, whereas it remained stable in lesions with FFR > 0.80. Conversely, iFR did not show a systematic trend at long-term after TAVI. However, iFR demonstrated a higher reclassification rate at follow-up compared with FFR (p = .02). In conclusions, in this exploratory study, only minor variations of coronary physiology indices were observed at long-term after TAVI. Nevertheless, caution should be exercised in the interpretation of borderline FFR and iFR values in severe AS.

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

Int J Cardiol: 14 Oct 2020; 317:37-41
Scarsini R, Lunardi M, Venturi G, Pighi M, ... Pesarini G, Ribichini F
Int J Cardiol: 14 Oct 2020; 317:37-41 | PMID: 32504719
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Impact:
Abstract

Serial change of perivascular fat attenuation index after statin treatment: Insights from a coronary CT angiography follow-up study.

Dai X, Yu L, Lu Z, Shen C, Tao X, Zhang J
Background
Perivascular fat attenuation index (FAI) was thought to be an indicator of active vessel inflammation surrounding coronary plaques. However, whether this index can be reduced by statin treatment remains unknown. We aimed to investigate the serial change of lesion-specific perivascular FAI as quantified by coronary computed tomography (CCTA) after statin treatment.
Methods
Consecutive patients with chest pain and intermediate likelihood of coronary artery disease were referred for baseline CCTA. Patients were retrospectively included if they were treated medically and underwent follow-up CCTA at 1-year to 1.5-year interval. Lesion-specific perivascular FAI, as well as other plaque features, were measured at baseline and follow-up.
Results
One hundred and eight patients (mean age 67.7 ± 11.1, 76 males) were included. A significant reduction of the FAI value was found for non-calcified plaques and mixed plaques (-68.0 HU ± 8.5 HU Vs. -71.5 HU ± 8.1 HU, p < .001 and - 70.5 HU ± 8.9 HU Vs. -72.8 HU ± 9.0 HU, p = .014). However, this improvement was not observed for calcified plaques (-70.6 HU ± 9.7 HU Vs. -71.7 HU ± 9.9 HU, p = .258). For non-calcified and mixed plaques, the volumes of non-calcified as well as low attenuation component was significantly reduced whereas total plaque volume and volume of calcified component increased. For calcified plaque, total plaque volume also demonstrated remarkable increase after statin treatment Conclusions: Lesion-specific perivascular FAI decreased at mid-term follow-up after statin treatment for non-calcified and mixed plaques. Perivascular FAI can be a potential imaging biomarker to monitor the anti-inflammation response to statin treatments.

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

Int J Cardiol: 14 Nov 2020; 319:144-149
Dai X, Yu L, Lu Z, Shen C, Tao X, Zhang J
Int J Cardiol: 14 Nov 2020; 319:144-149 | PMID: 32553595
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Impact:
Abstract

The impact of optimal medical therapy on patients with recurrent acute myocardial infarction: Subanalysis from the BleeMACS study.

Zhang D, Song X, Raposeiras-Roubín S, Abu-Assi E, ... Southern D, Kalpak O
Background
Acute myocardial infarction (AMI) recurrence is still high despite great progress in secondary prevention. Patients with recurrent AMI suffer worse prognosis compared to those with first AMI. The objective was to evaluate the effect of optimal medical therapy (OMT) on these patients with recurrent AMI.
Methods and results
Sub-analysis was performed including 13,343 patients with AMI from the international multicenter Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) registry. OMT was defined as the combination of aspirin, any P2Y12 inhibitor, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. Among 1285 patients with prior AMI, 56.8% received OMT prescription. Patients receiving OMT suffered from less congestive heart failure, peripheral artery disease, malignancy, and bleeding history. Kaplan-Meier survival estimates revealed that OMT was strongly related to decreased in all-cause death (4.2% vs. 10.1%, p < .001) and the composite endpoint of death/re-AMI (11.1% vs. 16.9%, p = .005) at 1-year follow-up. OMT was the independent protect factor of primary endpoint even after adjusting for multiple possible confounders (HR, 0.46; 95% CI, 0.27-0.78; p = .004). However, no significant difference was observed regarding re-AMI between OMT and non-OMT groups. OMT also reduced all-cause death in patients with recurrent AMI after propensity score matching.
Conclusions
The prescription of OMT was seriously insufficient in patients with recurrent AMI, especially high-risk patients, even though OMT was associated with improved prognosis. Further improvements in pharmacological therapy are needed to reduce subsequent recurrent events.

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

Int J Cardiol: 31 Oct 2020; 318:1-6
Zhang D, Song X, Raposeiras-Roubín S, Abu-Assi E, ... Southern D, Kalpak O
Int J Cardiol: 31 Oct 2020; 318:1-6 | PMID: 32598995
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Impact:
Abstract

Association of abnormal coronary sinus reflux with coronary slow flow and importance of the Thebesian valve.

Akşit E, Barutçu A, Şehitoğlu MH, Kırılmaz B, ... Gazi E, Tok ÖÖ
Background
The relationship between coronary slow flow (CSF) and coronary sinus (CS) reflux has not been previously studied. This study aimed to investigate the relationship between CSF and CS reflux and Thebesian valve presence as well as the relationship between CS reflux and serum annexin-V and ICAM-1 levels.
Methods
In this case-control study, patients were divided into two groups: CSF (n = 13) and control (n = 7) groups. CS flow parameters and Thebesian valve presence were evaluated by cardiac magnetic resonance (CMR). Moreover, serum ICAM-1 and annexin-V levels were measured.
Results
Regurgitation volume and regurgitation fraction, indicators of reflux flow in CS, were higher in the CSF group than in the control group (p = 0.039 and p = 0.019). Fewer Thebesian valves were observed in the CSF group than in the control group (p = 0.022). Furthermore, a positive correlation was found between regurgitation volume and regurgitation fraction and serum annexin-V and ICAM-1 levels (r = 0.813, p < 0.001 and r = 0.996, p < 0.001; r = 0.817, p < 0.001 and r = 0.993, p < 0.001, respectively).
Conclusions
This study revealed the significant relationship between CSF and reflux flow in CS. The fact that the patients in the CSF group have fewer Thebesian valves suggests the importance of the valve in preventing backward flow from the coronary vein. A positive correlation between serum ICAM-1 and annexin-V levels with regurgitation volume and regurgitation fraction indicates that after a certain threshold, CS reflux should be considered an abnormal condition.

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

Int J Cardiol: 14 Nov 2020; 319:26-31
Akşit E, Barutçu A, Şehitoğlu MH, Kırılmaz B, ... Gazi E, Tok ÖÖ
Int J Cardiol: 14 Nov 2020; 319:26-31 | PMID: 32858139
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Impact:
Abstract

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

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

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

Int J Cardiol: 13 Sep 2020; epub ahead of print
Miah N, Faxén UL, Lund LH, Venkateshvaran A
Int J Cardiol: 13 Sep 2020; epub ahead of print | PMID: 32941871
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Impact:
Abstract

Intravascular ultrasound guidance in the evaluation and treatment of left main coronary artery disease.

Case BC, Yerasi C, Forrestal BJ, Shlofmitz E, ... Mintz GS, Waksman R

Percutaneous coronary intervention (PCI) of left main coronary artery (LMCA) disease has become an acceptable revascularization strategy. Evaluating the extent and characteristics of obstructive disease of the LMCA by angiography is challenging and limited in its accuracy. In contrast, intravascular ultrasound (IVUS) provides accurate imaging of the coronary lumen as well as quantitative measurements and quantitative assessment of the vessel wall components. IVUS for LMCA PCI should be performed before, during, and after intervention; IVUS enhances every step in the procedure and is associated with a mortality advantage in comparison with angiographic guidance alone. In this review, we provide an update on LMCA PCI and the role of IVUS for lesion assessment and stent optimization. In addition, the latest clinical evidence of the benefits of IVUS-guided LMCA PCI as compared to angiography is reviewed.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 07 Oct 2020; epub ahead of print
Case BC, Yerasi C, Forrestal BJ, Shlofmitz E, ... Mintz GS, Waksman R
Int J Cardiol: 07 Oct 2020; epub ahead of print | PMID: 33039578
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Abstract

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

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

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

Int J Cardiol: 26 Aug 2020; epub ahead of print
Bos D, De Wolf D, Cools B, Eyskens B, ... Gewillig M, Heying R
Int J Cardiol: 26 Aug 2020; epub ahead of print | PMID: 32860844
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Abstract

Effect of exercise-based cardiac rehabilitation on clinical outcomes in patients with myocardial infarction in the absence of obstructive coronary artery disease (MINOCA).

He CJ, Zhu CY, Zhu YJ, Zou ZX, ... Zhai CL, Hu HL
Background
Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is characterized by clinical evidence of myocardial infarction with nonobstructive coronary stenosis on angiography (stenosis < 50%). Studies on the effect that exercise-based cardiac rehabilitation (CR) has on outcomes in MINOCA patients are lacking. Therefore, the purpose of this study was to determine the effect of exercise-based CR on clinical outcomes in patients with MINOCA.
Methods
A total of 524 participants with MINOCA were recruited in this prospective cohort study from August 2014 to October 2016 and followed for three years. We randomly divided 524 patients into an exercise-based cardiac rehabilitation group (CR+) and a control group (CR-). The CR+ group followed a home-based exercise-training program three times a week during the three years of moderate continuous training (MCT; 65%-75% of peak heart rate) on a bicycle or treadmill.
Results
After one year of follow-up, the Short Form 36 (SF-36) survey showed apparent improvement in the mean physical health score in the CR+ group compared with the CR- group (P < 0.01). During the three-year follow-up, all-cause mortality occurred in 60 individuals, and major adverse cardiovascular events (MACE) happened in 136 individuals. Kaplan-Meier curves indicated a significant reduction in all-cause mortality (log-rank P < 0.05) and MACE (log-rank P < 0.01) in the CR+ group. A multivariate Cox regression analysis indicated that exercise-based CR was associated with a significant reduction in all-cause mortality (hazard ratio [HR] = 0.483; 95% confidence interval [CI], 0.279-0.818; P < 0.01) and MACE (HR = 0.574; 95% CI, 0.403-0.827; P < 0.001).
Conclusions
A long-term exercise-based CR program was associated with superior physical health and a significant reduction in all-cause mortality and MACE in patients with MINOCA.

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

Int J Cardiol: 14 Sep 2020; 315:9-14
He CJ, Zhu CY, Zhu YJ, Zou ZX, ... Zhai CL, Hu HL
Int J Cardiol: 14 Sep 2020; 315:9-14 | PMID: 32416201
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Abstract

Smoking habits and progression of coronary and aortic artery calcification: A 5-year follow-up of community-dwelling Japanese men.

Pham T, Fujiyoshi A, Hisamatsu T, Kadowaki S, ... Ueshima H,
Background and aims
To examine whether smoking habits, including smoking amount and cessation duration at baseline, are associated with atherosclerosis progression.
Methods
At baseline (2006-08, Japan), we obtained smoking status, amount of smoking and time since cessation for quitters in a community-based random sample of Japanese men initially aged 40-79 years and free of cardiovascular disease. Coronary artery calcification (CAC) and aortic artery calcification (AAC) as biomarker of atherosclerosis was quantified using Agatston\'s method at baseline and after 5 years of follow-up. We defined progression of CAC and AAC (yes/no) using modified criteria by Berry.
Results
A total of 781 participants was analyzed. Multivariable adjusted odds ratios (ORs) of CAC and AAC progression for current smokers were 1.73 (95% CI, 1.09-2.73) and 2.47 (1.38-4.44), respectively, as compared to never smokers. In dose-response analyses, we observed a graded positive relationship of smoking amount and CAC progression in current smokers (multivariable adjusted ORs: 1.23, 1.72, and 2.42 from the lowest to the highest tertile of pack-years). Among the former smokers, earlier quitters (≥10.7 years) had similar ORs of the progression of CAC and AAC to that of participants who had never smoked.
Conclusions
Compared with never smokers, current smokers especially those with greater pack-years at baseline had higher risk of atherosclerosis progression in community-dwelling Japanese men. Importantly, the residual adverse effect appears to be present for at least ten years after smoking cessation. The findings highlight the importance of early avoidance or minimizing smoking exposure for the prevention of atherosclerotic disease.

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

Int J Cardiol: 31 Aug 2020; 314:89-94
Pham T, Fujiyoshi A, Hisamatsu T, Kadowaki S, ... Ueshima H,
Int J Cardiol: 31 Aug 2020; 314:89-94 | PMID: 32430214
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Abstract

Clinical and procedural implications of congenital vena cava anomalies in adults: A systematic review.

Shafi I, Hassan AAI, Akers KG, Bashir R, ... Weinberger JJ, Abidov A
Background
Although congenital vena cava (CVC) anomalies in adults have implications for surgical and radiological interventions, the literature is scare and disparate. The aim of this systematic review was to assess cardiovascular clinical and procedural implications of CVC anomalies in adults without congenital heart disease.
Methods and results
We searched PubMed and EMBASE from database conception through October 2018 for English-language studies describing the epidemiology of CVC anomalies or their clinical or procedural implications in humans. Two independent reviewers screened 7093 records and identified 16 relevant studies. We found two major implications of CVC anomalies: 1) congenital inferior vena cava (CIVC) anomalies are associated with a 50-100-fold higher risk of deep venous thrombosis, particularly among younger patients, and 2) persistent left superior vena cava (PLSVC) is associated with a 2-3-fold higher risk of supraventricular arrhythmias. PLSVC also poses technical challenges to cardiovascular electronic device implantation, requiring alterations in surgical approach and lengthening procedure and X-ray exposure times. Due to the large disparity in reported prevalence rates of CIVC anomalies, we performed a meta-analysis of CIVC anomaly prevalence including 8 studies, which showed a weighted prevalence of 6.8% (95% CI, 4.5-9.2%).
Conclusion
These findings challenge the notion that CVC anomalies are rare and asymptomatic in adults. Rather, the literature indicates that CVC anomalies are not uncommon and have important clinical and procedural implications. To further understand the prevalence and implications of CVC anomalies, a robust US population-based study and nationwide registry is warranted in the current era of venous interventions.

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

Int J Cardiol: 14 Sep 2020; 315:29-35
Shafi I, Hassan AAI, Akers KG, Bashir R, ... Weinberger JJ, Abidov A
Int J Cardiol: 14 Sep 2020; 315:29-35 | PMID: 32434672
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Abstract

Association between personality profile and subclinical atherosclerosis: The role of genes and environment.

Medda E, Fagnani C, Alessandri G, Baracchini C, ... Tarnoki DL, Stazi MA
Background
The mechanism underlying the association between personality profile and subclinical atherosclerosis is poorly understood. This study explores the association between personality, carotid atherosclerosis and arterial stiffness, and the contribution of genes and environment to this association.
Methods
Early atherosclerotic traits, including carotid intima-media thickness (CCA-IMT), aortic pulse wave velocity (PWVao) and heart rate, were assessed in 318 adult twins, who also completed a Big Five personality questionnaire. Using the co-twin control approach, the association between intra-pair differences in clinical and personality scores was assessed in dizygotic (DZ) and monozygotic (MZ) twins separately.
Results
An association between CCA-IMT and extroverted personality, as well as between PWVao and openness to experience was detected. The inverse association between CCA-IMT and extraversion was persistent in DZ and disappeared in MZ twins, suggesting genetic confounding. In contrast, the association between PWVao and openness to experience was of the same magnitude in DZ and MZ twins, thus surviving the adjustment for genetic and shared environmental factors.
Conclusions
This study highlights that the association between some psychological factors and cardiovascular traits may be partly explained by genetic factors. This result may provide support for the feasibility of prevention programs based on assessing familiarity for personality disorders to detect genetic risk for subclinical cardiovascular disease.

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

Int J Cardiol: 30 Sep 2020; 316:236-239
Medda E, Fagnani C, Alessandri G, Baracchini C, ... Tarnoki DL, Stazi MA
Int J Cardiol: 30 Sep 2020; 316:236-239 | PMID: 32442593
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Abstract

Magnetic resonance phase contrast velocity mapping for flow quantification in irregular heart rhythms using radial k-space ultrashort echo time imaging.

Hell MM, Francis JM, d\'Arcy J, Robson MD, ... Achenbach S, Myerson SG
Background
Phase contrast velocity mapping sequences utilising ultrashort echo time (UTE) radial k-space sequences have been used to reduce intravoxel dephasing at high velocities. We evaluated the accuracy of the UTE flow sequence for mitral regurgitation (MR) quantification, including patients with atrial fibrillation.
Methods
Forty patients underwent cardiac MRI for indirect MR quantification by assessment of aortic flow using a UTE phase contrast sequence (TE 0.65 ms) combined with left ventricular stroke volume. Retrospective ECG-gating was used in sinus rhythm (30 patients), prospective ECG-triggering in atrial fibrillation (10). MR was also quantified by a standard phase contrast sequence (TE 2.85 ms, standard flow method) and by comparing stroke volumes (volumetric method).
Results
UTE flow-derived MR measurement showed modest agreement in sinus rhythm (95% limits of agreement: ±38.2 ml; ±29.8%) and atrial fibrillation (±33.7 ml; ±30.3%) compared to standard flow assessment. There was little systematic bias in sinus rhythm (mean offset -4.4 ml /-3.5% compared to standard flow assessment), but a slight bias towards greater regurgitation in atrial fibrillation (+15.2 ml /+14.0%). There were wider limits of agreement between the UTE flow method and volumetric method than between the regular flow method and the volumetric method in sinus rhythm (±48.4 ml; ±36.4%; mean offset: -12.2 ml /-9.0%) and similar limits of agreement in atrial fibrillation (±29.6 ml; 25.8%; +12.0 ml /+10.3%).
Conclusions
UTE flow imaging is inferior to conventional flow techniques for MR assessment in patients with sinus rhythm as well as atrial fibrillation. However, the number of atrial fibrillation patients in this initial study is small.

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

Int J Cardiol: 14 Oct 2020; 317:211-215
Hell MM, Francis JM, d'Arcy J, Robson MD, ... Achenbach S, Myerson SG
Int J Cardiol: 14 Oct 2020; 317:211-215 | PMID: 32439365
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Abstract

Impact of concomitant deep or superficial venous thrombosis of the legs on survival of patients with pulmonary embolism.

Keller K, Hobohm L, Münzel T, Ostad MA
Background
Pulmonary embolism (PE) is a frequent cause of death and morbidity. A few studies suggest that clot burden in pulmonary artery bed is related to PE patients\' survival, but the impact of concomitant deep venous thrombosis and/or thrombophlebitis (DVT) on short-term survival of PE patients remains unclear. Thus, we aimed to investigate the impact of DVT on adverse outcomes in PE patients.
Methods
Patients of the nationwide inpatient sample with PE (ICD-code I26) were stratified for DVT (ICD-code I80) and compared for patient characteristics, risk stratification markers, treatments and outcomes. Impact of concomitant DVT on adverse in-hospital outcomes was tested.
Results
Overall, 346,586 PE patients (53.3% females) were included in this analysis. Among these, in 126,477 (36.5%) DVT was coded. PE patients with DVT were younger, less often of female sex and VTE risk-factors (surgery, cancer) as well as cardiovascular and pulmonary diseases were less prevalent compared with isolated PE. PE patients with DVT showed a significant better survival (5.4% vs. 20.2%, P < .001) and lower adverse in-hospital event rate (9.7% vs. 27.4%, P < .001) compared to patients with isolated PE. Lower risk for in-hospital mortality (OR 0.238 [95%CI 0.232-0.245], P < .001) and adverse in-hospital events (OR 0.302 [95%CI 0.295-0.309], P < .001) were respectively independent of age, gender, comorbidities and reperfusion-treatments.
Conclusions
Concomitant DVT affects survival of PE patients. Patients with an isolated PE had higher rate of in-hospital mortality and adverse in-hospital events. Our data suggest, that peripheral thrombus burden in PE with concomitant DVT might be less harmful in comparison to isolated PE with a probably larger thrombus burden.

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

Int J Cardiol: 14 Sep 2020; 315:92-98
Keller K, Hobohm L, Münzel T, Ostad MA
Int J Cardiol: 14 Sep 2020; 315:92-98 | PMID: 32445886
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Abstract

Reproductive health professional\'s reported knowledge on diagnosis and management of rheumatic heart disease in pregnant women in Maputo, Mozambique.

Jamal K, Raivoso M, Daniel A, Mocumbi A
Background
Rheumatic heart disease (RHD) poses a threat to African women in their reproductive years, being an important cause of maternal mortality and poor foetal outcomes. Timely diagnosis and adequate management reduce significantly obstetric complications. Our study aimed to describe the knowledge of diagnosis and management of RHD in pregnant women among reproductive health professionals (RHP) working in a highly endemic area.
Methods
The study that took place in May/2017 in two conveniently selected health facilities. Doctors (residents and specialists) and mid-level (maternal and child health nurses/technicians, MLRHP) were invited to respond to an anonymous, self-administered and standardized survey (electronic and paper-based questionnaires), which contained closed and open-ended questions on pregnancy-related RHD diagnosis, treatment and complications. The responses were coded and analysed using SPSS version 20.
Results
Seventy-three RHP participated (27 doctors, 46 MLRHP). While RHP understand the fetal 49 (67%) and maternal 57 (53%) outcomes in presence of RHD, they are unprepared to diagnose, manage and refer them adequately.
Conclusion
RHP constitute a group that can be targeted for decentralization of diagnosis and management of RHD, a strategy that may be crucial to reduce maternal mortality by indirect causes in low-middle income countries.

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

Int J Cardiol: 14 Oct 2020; 317:207-210
Jamal K, Raivoso M, Daniel A, Mocumbi A
Int J Cardiol: 14 Oct 2020; 317:207-210 | PMID: 32450276
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Impact:
Abstract

Functional mitral regurgitation and cardiac resynchronization therapy in the \"era\" of trans-catheter interventions: Is it time to move from a staged strategy to a tailored therapy?

Gavazzoni M, Taramasso M, Zuber M, Pozzoli A, ... Oliveira D, Maisano F

Cardiac resynchronization therapy (CRT) has been associated to left ventricle (LV) remodelling, reduction of functional mitral regurgitation (FMR) and clinical improvement in patients with heart failure and reduced ejection fraction (HFrEF). The prevalence of significant FMR in patients with LV dyssynchrony that are candidate to CRT is up to 40%. Current approach in patients with FMR undergoing CRT consists of re-evaluation of the amount of FMR following a waiting period of at least 3 months after the implant. In case of persistent significant FMR despite CRT and guideline directed medical therapy, trancatheter Mitral Valve repair (TMVR) is an important option to improve quality of life and prognosis. This stepwise approach does not take into account the probability of the individual response to CRT and the availability of TMVR solutions that are safe and effective in high risk patients. We reviewed the effects of CRT on FMR, the prognostic role of persistence of FMR after CRT treatment and the impact of treatment of FMR in patients CRT non responders. We aimed to point out the limits of current step-wised approach in light on more recent evidence regarding FMR treatment. A new, \"tailored\" approached is proposed.

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

Int J Cardiol: 14 Sep 2020; 315:15-21
Gavazzoni M, Taramasso M, Zuber M, Pozzoli A, ... Oliveira D, Maisano F
Int J Cardiol: 14 Sep 2020; 315:15-21 | PMID: 32456957
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Impact:
Abstract

Cilostazol and peripheral artery disease-specific health status in ambulatory patients with symptomatic PAD.

Mohammed M, Gosch K, Safley D, Jelani QU, ... Abbott JD, Smolderen KG
Background
Improvement of symptoms and functional status is one of the main peripheral artery disease (PAD) treatment goals but pharmacological options are limited. The objective of this study was to assess the use of cilostazol and its association with patient-reported health status quantified by the Peripheral Artery Questionnaire (PAQ).
Methods
Initiation of cilostazol therapy was assessed in 567 patients in the US cohort of PORTRAIT between June 2011 and December 2015. Patients with heart failure history, on cilostazol prior to enrollment, with no baseline or follow-up PAQ scores were excluded. Health status over time was quantified using linear mixed models adjusting for baseline PAQ scores and patient characteristics.
Results
Of the 567 cilostazol-naïve patients, 65 (11%) were started on cilostazol. Mean age was 68.5 ± 9.6 years, 43% were female and 71.1% white. There was no significant difference in the mean PAQ score changes from baseline to 12 months between the cilostazol and non-cilostazol group, with difference of 3.8 [CI (-2.6, 10.1), p = .24] for summary scores, 1.6 [CI (-5.5, 8.6), p = .66] for quality of life, 3.6 [CI (-4.3, 11.6), p = .37] for symptoms, 6.2 [CI (-3.1, 15.5), p = .19] for physical limitation and 3.2 [CI (-3.9, 10.2), p = .38] for social limitation scores.
Conclusions
We found a low rate of cilostazol use and while there was no significant association between cilostazol initiation and subsequent health status, the ability to define small differences in health status was limited due to the small sample size.

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

Int J Cardiol: 30 Sep 2020; 316:222-228
Mohammed M, Gosch K, Safley D, Jelani QU, ... Abbott JD, Smolderen KG
Int J Cardiol: 30 Sep 2020; 316:222-228 | PMID: 32464249
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Abstract

Sleep disordered breathing in adults living with a Fontan circulation and CPAP titration protocol.

Nanayakkara B, Lau E, Yee B, Gauthier G, ... Celermajer D, Cordina R
Background
Fontan-type single ventricle physiology has exquisite respiratory dependence. Obstructive sleep apnoea (OSA) and continuous positive airway pressure (CPAP) are likely to have deleterious haemodynamic consequences.
Methods
Asymptomatic and symptomatic Fontan-adults underwent diagnostic polysomnography; The overnight CPAP titration employed echocardiography and peripheral venous pressure (PVP) measurements to determine the upper limit of pressure prior to haemodynamic deterioration (> 20% rise in PVP or 20% fall in stroke volume).
Results
In asymptomatic adults (n = 7), mean age was 32 ± 9 years and awake oxygen saturations were 92 ± 3%. There was no significant OSA with Apnoea Hypopnoea Index (AHI) of 0.6 ± 1.1 events/h and mild nocturnal hypoxaemia (nadir 89 ± 4%). In sleepy patients (n = 7, age 36 ± 7 years, awake saturations 84 ± 5%, NYHA Class III ± I), sleep efficiency was 81 ±10% with mild OSA on average (AHI 7.9 ± 10.1) events/h) and marked desaturation (nadir of 76 ± 6%); Most episodes were obstructive in nature. BMI correlated with AHI (n = 14, R = 0.7, p = .005). Two of 7 (29%) had moderate OSA characterised by an early fall in PVP, 3 ± 1 mmHg and a 2 ± 1 mmHg increase at event termination. CPAP was successfully applied through in-laboratory titration (stroke volume fall was the end-point determinant in both).
Conclusion
Our cohort of asymptomatic adults did not have significant SDB but SDB was common in sleepy patients. Fontan-adults with symptoms suggestive of SDB should be offered polysomnography and can be safely treated with CPAP employing echocardiographic titration.

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

Int J Cardiol: 14 Oct 2020; 317:70-74
Nanayakkara B, Lau E, Yee B, Gauthier G, ... Celermajer D, Cordina R
Int J Cardiol: 14 Oct 2020; 317:70-74 | PMID: 32464248
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Impact:
Abstract

Poorly suited heart valve prostheses heighten the plight of patients with rheumatic heart disease.

Scherman J, Zilla P

Rheumatic heart disease (RHD) still affects more patients globally than degenerative valve disease. The vast majority of these patients live in low- to middle-income countries. Once symptomatic, they will need heart valve surgery. Unfortunately, prosthetic valves perform poorly in these patients given their young age, the high incidence of multi-valve disease, late diagnoses and often challenging socio-economic circumstances. Notwithstanding the fact that better valve designs would ideally be available, ill-informed decision making processes between bioprosthetic and mechanical valves are contributing to the poor results. In the absence of multicentred, randomised clinical trials, comparing the current generations of bioprostheses with mechanical valves across all age groups Western guidelines tend to be uncritically applied. As a consequence, mechanical valves are being implanted into patients who are often not able to deal with anticoagulation while bioprosthetic valves may be overly shunned for fear of reoperations. Almost sixty years after the advent of cardiac surgery heart valve prostheses have eventually undergone improvements and several potentially disruptive developments are on the horizon. Until they materialise, however, choices between contemporary valve prostheses need to be made on the basis of individual risk and life-expectancy rather than an uncritical implementation of guidelines that were derived for very different patients and under distinctly different conditions. Given the fast expansion of cardiac surgery in middle-income countries and a growing number of independently operating centres in low-income countries a critical appraisal of facts underlying the choice of heart valve prostheses for patients with RHD seems opportune.

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

Int J Cardiol: 31 Oct 2020; 318:104-114
Scherman J, Zilla P
Int J Cardiol: 31 Oct 2020; 318:104-114 | PMID: 32464247
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Impact:
Abstract

Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE.

Benza RL, Corris PA, Klinger JR, Langleben D, ... Busse D, Hoeper MM
Background
RESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement.
Methods
RESPITE was a 24-week, uncontrolled pilot study (n = 61). Differences in functional, hemodynamic, and cardiac function parameters, REVEAL risk score (RRS), and biomarkers were compared between responders (free from clinical worsening, World Health Organization functional class I/II, and ≥30 m improvement in 6-min walking distance at Week 24) and non-responders.
Results
Of 51 patients (84%) completing RESPITE, 16 (31%) met the responder endpoint. At baseline, there were significant differences between responders and non-responders in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth/differentiation factor 15 (GDF-15), and RRS, whereas there were no differences in hemodynamics or cardiac function. At Week 24, responders had significant improvements in pulmonary arterial compliance, pulmonary vascular resistance, and mean pulmonary arterial pressure, while non-responders showed no significant change. Cardiac efficiency and stroke volume index significantly improved irrespective of responder status.
Conclusions
NT-proBNP, GDF-15, and RRS were identified as potential predictors of response in patients switching from PDE5i to riociguat. Further prospective controlled studies are needed to confirm the association of these parameters with response.

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

Int J Cardiol: 14 Oct 2020; 317:188-192
Benza RL, Corris PA, Klinger JR, Langleben D, ... Busse D, Hoeper MM
Int J Cardiol: 14 Oct 2020; 317:188-192 | PMID: 32461118
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Impact:
Abstract

Impact of COAPT trial exclusion criteria in real-world patients undergoing transcatheter mitral valve repair.

Iliadis C, Metze C, Körber MI, Baldus S, Pfister R
Background
The generalizability of the COAPT trial results on the benefit of TMVR in patients with secondary mitral regurgitation is unclear.
Methods
Functional and long-term clinical outcome were examined in 122 consecutive patients with secondary mitral regurgitation and reduced ejection fraction undergoing TMVR. \"COAPT-like\" patients were defined according to principal COAPT inclusion/exclusion criteria if all of the following was fulfilled: symptomatic mitral regurgitation grade 3+ or more according to American guidelines; left ventricular ejection fraction ≥ 20%, left ventricular end-systolic dimension ≤ 70 mm, estimated pulmonary artery systolic pressure ≤ 70 mmHg, mitral valve orifice area ≥ 4 cm, no prior mitral valve procedure, no right sided congestive heart failure, no COPD requiring home oxygen therapy and NYHA class less than IVb.
Results
51% of 122 patients (mean age 74 ± 10 years, 76% male) showed COAPT-like characteristics. COAPT-like patients showed a significantly lower hazard for the composite endpoint of mortality and heart failure hospitalization (HR 0.51, 95%CI 0.30-0.89, p = .017) during a mean follow-up of 16 ± 6 months, with an estimated 1-year event rate of 20% vs 43%, respectively. The improvement in functional outcomes 6 min walking distance (76 ± 136 m vs. 31 ± 90 m), Minnesota Living with Heart Failure Questionnaire (-6 ± 19 vs. -10 ± 23) and Short Form 36 physical component score (3.8 ± 10 vs. 5.5 ± 11) was similar in COAPT-like and the other patients.
Conclusion
In this first real world cohort half of the patients undergoing TMVR showed COAPT-like characteristics and these patients showed a substantially better clinical outcome. The mid-term functional benefit was similar in COAPT-like and other patients.

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

Int J Cardiol: 30 Sep 2020; 316:189-194
Iliadis C, Metze C, Körber MI, Baldus S, Pfister R
Int J Cardiol: 30 Sep 2020; 316:189-194 | PMID: 32470537
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Impact:
Abstract

Cardiovascular and abdominal flow alterations in adults with morphologic evidence of liver disease post Fontan palliation.

Abbasi Bavil E, Yang HK, Doyle MG, Kim TK, ... Mertens L, Wald RM
Background
Although morphologic abnormalities in the liver are commonly encountered post Fontan palliation, the relationships between hepatic morphology, vascular flows, and clinical status remain incompletely understood. We therefore aimed to explore flow characteristics in hepatic and intestinal vessels and to examine cardiovascular associations with liver disease.
Methods
This was a retrospective study of adults post Fontan palliation undergoing clinically indicated cardiovascular magnetic resonance imaging (MRI). Patients were included if MRI flow quantification was available for cardiac, hepatic and intestinal vessels; patients were excluded if phase-contrast flow imaging was insufficient for analysis.
Results
Thirty patients were studied (median age at MRI 28.5 years [range 19-47]). Eighteen subjects (60%) were classified as having morphologic liver disease according to validated criteria based on available MRI imaging. Abdominal and cardiovascular flows were quantified. Patients with morphologic liver disease had a 41% reduction in superior mesenteric artery (211 ± 124 versus 358 ± 181 mL/min/m, p = .004), a 36% reduction in hepatic vein (496 ± 247 versus 778 ± 220 mL/min/m, p = .01), a 31% reduction in portal vein (399 ± 133 versus 580 ± 159 mL/min/m, p = .004), and an 18% reduction in Fontan pathway flows (1358 ± 429 versus 1651 ± 270 mL/min/m, p = .04) compared with the remaining population. Adverse cardiovascular events were not associated with morphologic liver disease.
Conclusion
Morphologic liver disease appears to be associated with flow alterations within the heart, liver and intestine post Fontan palliation. These novel observations suggest that a potential relationship exists between morphologic disease and vascular flows thereby providing further insights into the pathophysiology of liver disease in this high-risk population.

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

Int J Cardiol: 14 Oct 2020; 317:63-69
Abbasi Bavil E, Yang HK, Doyle MG, Kim TK, ... Mertens L, Wald RM
Int J Cardiol: 14 Oct 2020; 317:63-69 | PMID: 32470536
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Abstract

Genetic homozygosity in a diverse population: An experience of long QT syndrome.

Mahdieh N, Khorgami M, Soveizi M, Seyed Aliakbar S, Dalili M, Rabbani B
Background
Genomic variations have shown an ethnic-specific pattern within various cohorts. Genetic variants of KCNQ1, KCNH2, SCN5A and KCNE1 causing LQT syndrome have been described in many populations. In this article the spectrum of variants of these genes is presented in Iranian patients.
Methods
102 unrelated individuals diagnosed with LQT were enrolled in this study. Clinical and electrocardiogram (ECG) data of 95 patients were documented, and analyzed by expert pediatric cardiologists. Coding regions and exon-intron boundaries were amplified and sequenced. Segregation analysis was done for novel variants as well as in silico analyses.
Results
Sixty nine of 95 cases (73%) had Schwartz score of ≥3.5. The causal variants were found in 31 cases (9 novel variants). 21 patients had KCNQ1 (LQTS1) of which15 patients were homozygous for KCNQ1 variants, 9 of these patients (29%) had a Jervell and Lange-Nielsen phenotype. 4 patients had KCNH2 (LQTS2) variants, 7 cases had SCN5A had heterozygous variants, and 2 cases had heterozygous variants in KCNE1 (LQTS5). 19 variants were missense, 3 were nonsense, and 3 were frameshifts. There was one large deletion and 3 intronic variants.
Conclusion
The yield of genetic testing and the genotype profile of LQTS patients in Iran is different from reports elsewhere, with lower overall yield and with 48% having homozygous states.

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

Int J Cardiol: 30 Sep 2020; 316:117-124
Mahdieh N, Khorgami M, Soveizi M, Seyed Aliakbar S, Dalili M, Rabbani B
Int J Cardiol: 30 Sep 2020; 316:117-124 | PMID: 32470535
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