Journal: Int J Cardiol

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Abstract

Evolving use of natriuretic peptide receptor type-C as part of strategies for the treatment of pulmonary hypertension due to left ventricle heart failure.

Egom EE, Maher V, El Hiani Y
Pulmonary hypertension (PH) due to left ventricular heart failure (LV-HF) is a disabling and life-threatening disease for which there is currently no single marketed pharmacological agent approved. Despite recent advances in the pathophysiological understanding, there is as yet no prospect of cure, and the majority of patients continue to progress to right ventricular failure and die. There is, therefore an urgent unmet need to identify novel pharmacological agents that will prevent or reverse the increase in pulmonary artery pressures while enhancing cardiac performance in PH due to LV-HF. In the present article, we first focused on the Natriuretic Peptide Receptor type C (NPR-C) based therapeutic strategies aimed at lowering pulmonary artery pressure. Second, we reviewed potential NPR-C therapeutic strategies to reverse or least halt the detrimental effects of diastolic dysfunction and impaired nitic oxide signalling pathways, as well as possibilities for neurohumoral modulation.

Int J Cardiol: 01 Jun 2018; epub ahead of print
Egom EE, Maher V, El Hiani Y
Int J Cardiol: 01 Jun 2018; epub ahead of print | PMID: 29885823
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Abstract

Role of new imaging modalities in pursuit of the vulnerable plaque and the vulnerable patient.

Raggi P, Pontone G, Andreini D
Numerous biomarkers and imaging modalities were investigated during the past few decades to identify patients harboring plaques at high risk of rupturing and causing catastrophic events. The classical description of a vulnerable plaque included a large lipid core, covered by a thin fibrous cap and evidence of inflammation especially around the hinge points of the plaque. Unfortunately, the search has resulted to a large extent in a failure to accurately identify the site of a future event. In time the search focus switched to the vulnerable patient rather than the individual vulnerable plaques, but the debate continues as to the more appropriate approach to risk assessment. This review discusses the most recent developments in molecular, anatomical and functional imaging directed at identifying a patient at high-risk of coronary artery disease events.

Int J Cardiol: 31 Dec 2017; 250:278-283
Raggi P, Pontone G, Andreini D
Int J Cardiol: 31 Dec 2017; 250:278-283 | PMID: 29102056
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Abstract

Epigenetics and cardiovascular regenerative medicine in the elderly.

Costantino S, Camici GG, Mohammed SA, Volpe M, Lüscher TF, Paneni F
Cardiovascular disease (CVD) is a recognized age-dependent condition whose incidence is set to increase due to the gradual aging of the population. Moreover, ischemic cardiovascular diseases (i.e. stroke, myocardial infarction, critical limb ischemia) requiring blood vessel growth are associated with a worse outcome in elderly patients. Therefore, understanding the molecular cues regulating the vascular repair process is of paramount importance to prevent undesirable cardiovascular complications in this setting. A growing body of evidence suggests that epigenetic modifications - changes to the genome that do not involve changes in DNA sequence - may significantly derail gene expression trajectories during the life course, thus affecting molecular phenotype and functionality of angiogenic cells, namely mature endothelial cells (ECs), endothelial progenitor cells (EPCs), and bone-marrow (BM)-derived angiogenic cells. In the present review, we discuss the emerging role of epigenetics in age-related impairment of the angiogenic process. Specifically, the following aspects are critically addressed: i) defective angiogenic process in aging; ii) impact of epigenetics (DNA methylation, histone modifications, microRNAs, long noncoding RNAs) on phenotype and function of ECs and BM-derived angiogenic cells; iii) clinical perspectives on epigenetic biomarkers and reprogramming approaches for autologous transplantation. A scrutiny characterization of the \"old epigenome\" may provide unprecedented insights to develop preventive strategies and regenerative therapeutic interventions in the elderly.

Int J Cardiol: 31 Dec 2017; 250:207-214
Costantino S, Camici GG, Mohammed SA, Volpe M, Lüscher TF, Paneni F
Int J Cardiol: 31 Dec 2017; 250:207-214 | PMID: 28988828
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Abstract

Cell-derived microvesicles in cardiovascular diseases and antiplatelet therapy monitoring - A lesson for future trials? Current evidence, recent progresses and perspectives of clinical application.

Tomaniak M, Gąsecka A, Filipiak KJ
Circulating cell-derived microvesicles (MV) represent a subject of increasing interest in recent years as potential effectors in thrombosis, inflammation and vascular injury. Although several studies demonstrated an association between MV plasma concentrations and clinical manifestations of atherosclerosis as well as a clear effect of cardiovascular pharmacotherapy on MV formation pattern, the application of this promising biomarkers in clinical cardiology has been hindered so far due to heterogeneity of the hitherto studies employing non-standardized methodologies. Recently great progresses have been done and international initiatives were started to unify the pre-analytical and analytical procedures, improve the comparison of measurements between the laboratories and increase detector sensitivity of flow cytometry - a golden standard for MV assessment. Likewise, the concept of a "therapeutic window" of P2Y12 inhibitor therapy was introduced, as the prognostic significance of bleeding consequences is equally important with that of ischemic events, particularly with the expanding use of more potent P2Y12 inhibitors. In this review we summarize currently available studies on circulating MV in terms of cardiovascular diagnosis, risk stratification and influence of antiplatelet agents on the MV release to postulate possible future role of MV as supplementary biomarker in monitoring of individual response to antiplatelet therapy. Methodological pitfalls faced in the previous studies and obstacles that need to be addressed before further trials and translation of MV-based assays into clinical practice were defined.

Int J Cardiol: 27 Oct 2016; 226:93-102
Tomaniak M, Gąsecka A, Filipiak KJ
Int J Cardiol: 27 Oct 2016; 226:93-102 | PMID: 27792994
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Abstract

A review of the coronary applications of the drug coated balloon.

Jackson D, Tong D, Layland J
The drug coated balloon (DCB) platform offers several theoretical benefits over stent-based technologies. It allows the homogenous transfer of an anti-proliferative drug to reduce neo-intimal hyperplasia whilst potentially maintaining normal vessel anatomy and function. They also avoid the introduction of an additional stent layer in the context of in-stent restenosis. The data pertaining to the treatment of de-novo coronary disease still favors the new generation of drug eluting stents. DCB may, however, have a role in the context of challenging coronary anatomy and small vessel disease where results with stent insertion are poor. The body of evidence supporting the role of DCB in the treatment of in-stent restenosis is more substantial and appears to yield similar results to DES without the introduction of an additional stent layer. Further trials are required to clarify the ideal duration of dual anti-platelet treatment following DCB use and to further elucidate the ideal clinical context for their use.

Int J Cardiol: 27 Oct 2016; 226:77-86
Jackson D, Tong D, Layland J
Int J Cardiol: 27 Oct 2016; 226:77-86 | PMID: 27792992
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Abstract

Outcomes of transcatheter aortic valve replacement without predilation of the aortic valve: Insights from 1544 patients included in the SOURCE 3 registry.

Dumonteil N, Terkelsen C, Frerker C, Collart F, ... Lefèvre T,
Aims
To investigate the impact of transcatheter aortic valve replacement (TAVR) without preliminary balloon aortic valvuloplasty (pre-BAV) on periprocedural outcomes in a large, real-world registry.
Methods and results
The SOURCE 3 registry was an observational, multi-center, single-arm study of patients with severe, symptomatic aortic stenosis at high surgical risk treated with the SAPIEN 3 transcatheter heart valve (THV). Procedural and 30-day outcomes were compared between two groups of 772 patients each (retrospectively matched) with or without pre-BAV. All baseline clinical, echocardiographic, and anatomical valve characteristics were comparable between groups except for Society of Thoracic Surgeons (STS) score, which was lower in the direct TAVR group (6.0 ± 5.9 vs 7.8 ± 8.3; p = 0.003). In the direct TAVR group, there were less post-dilatations (8.1% vs. 13.1%, p = 0.002), shorter procedural time (70.9 ± 39.8 min vs 73.0 ± 32.2 min, p = 0.033) and fluoroscopy time (13.4 ± 7.0 min vs 14.9 ± 7.4 min, p < 0.001). Other procedural outcomes and echocardiographic variables at 30 days did not differ significantly between the two groups: safety endpoint (10.4% with pre-BAV vs 13.5% with direct TAVR, p = 0.059), mortality (2.1% vs 2.3%, p = 0.730), disabling strokes (0.4% vs 0.5%, p = 0.704), and moderate to severe paravalvular leak (PVL) (3.2% vs 2.2%, p = 0.40). Unexpectedly, new permanent pacemaker implantation and life-threatening bleeds were less frequently observed with pre-BAV group than with direct TAVR (10.4% vs 13.9%, p = 0.032 and 3.5% vs 6.5%, p = 0.007, respectively).
Conclusion
In this large TAVR dataset, direct implantation of the SAPIEN 3 THV without pre-BAV was feasible and safe and resulted in shorter procedures, without impact on 30-day prosthesis function and PVL.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:32-37
Dumonteil N, Terkelsen C, Frerker C, Collart F, ... Lefèvre T,
Int J Cardiol: 30 Nov 2019; 296:32-37 | PMID: 31256993
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Abstract

The association between pulmonary hypertension and stroke: A systematic review and meta-analysis.

Shah TG, Sutaria JM, Vyas MV
Background
Pulmonary hypertension is associated with atrial fibrillation and paradoxical embolism. Yet, the association between pulmonary hypertension and stroke has not been well studied.
Methods
We reviewed Medline and Embase from inception to December 1, 2018, to identify observational studies reporting prevalence of stroke in adult patients with pulmonary hypertension. We sought studies that included patients with pulmonary hypertension secondary to any etiology except left heart failure, and excluded studies that reported rates of perioperative stroke. We conducted random effects meta-analyses to obtain pooled prevalence of stroke in patients with pulmonary hypertension, and pooled unadjusted odds ratio of stroke in patients with pulmonary hypertension compared to those without.
Results
We included 14 studies including 32,523 participants of which 2976 (9.2%) had pulmonary hypertension, and 727 (2.2%) had a stroke. The pooled prevalence of stroke in patients with pulmonary hypertension was 8.0% [95% confidence interval (CI), 5.1%-10.9%, I 91.9]. The pooled unadjusted odds ratio of stroke in patients with pulmonary hypertension compared to those without was 1.46 (95% CI, 1.07-1.99, I 55.6, n = 7 studies).
Conclusion
Stroke is a major non-cardiac morbidity in patients with pulmonary hypertension, requiring further evaluation to determine its etiology, and measures to reduce its risk.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Nov 2019; 295:21-24
Shah TG, Sutaria JM, Vyas MV
Int J Cardiol: 14 Nov 2019; 295:21-24 | PMID: 31402157
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Abstract

Delayed prolongation of the QRS interval in patients with left ventricular dysfunction.

Rav-Acha M, Nujidat A, Farkash R, Medina A, ... Glikson M, Hasin T
Aims
Patients with left ventricular dysfunction (LVD) and prolonged QRS on surface electrocardiogram are at increased risk for heart failure and death and may benefit from resynchronization therapy. Patients with initial narrow QRS may prolong their QRS during the disease course. The occurrence of delayed QRS prolongation, its predictors and associated risk of heart failure hospitalizations (HFH) or death are currently unknown and the subject of this investigation.
Methods & results
Patients with LVD, QRS < 120 ms and available follow-up ECGs were retrospectively evaluated for persistent unprovoked QRS prolongation >130 ms. Impact on mortality or HFH was assessed using Cox regression with QRS > 130 ms as a time dependent covariate. Following 178 patients for 30 (10;59) median (IQR) months, 28 (16%) patients prolonged their QRS to >130 ms, reaching a QRS duration of 154 ± 29 ms; LBBB pattern was diagnosed among 14 (50%) patients. Patients with delayed QRS prolongation were older (71.9 ± 11.8 vs 64.4 ± 15.1 years p = 0.014), had larger left ventricle and left atrial diameters (6.3 ± 0.9 vs 5.7 ± 0.9 cm p = 0.010; 4.9 ± 0.6 vs 4.5 ± 0.7 cm p = 0.006, respectively) and wider baseline QRS (104.8 ± 12.6 vs 91.4 ± 14.5 ms p < 0.001) which was linearly associated with late QRS prolongation (p for trend<0.0001). In a multivariable model, age, baseline QRS width and left atrial diameter were significantly associated with delayed QRS prolongation. QRS prolongation at follow-up was independently associated with risk of death or HFH (HR 7.426, 95% CI3.017-18.280, p < 0.0001).
Conclusion
QRS prolongation occurs in a significant proportion of patients with LVD and portends adverse outcome. Advanced age, prolonged QRS and larger left atria are potential predictors. Routine monitoring is justified and physicians may choose to plan ahead for resynchronization therapy in patients at risk for QRS prolongation.

Copyright © 2019. Published by Elsevier B.V.

Int J Cardiol: 30 Nov 2019; 296:71-75
Rav-Acha M, Nujidat A, Farkash R, Medina A, ... Glikson M, Hasin T
Int J Cardiol: 30 Nov 2019; 296:71-75 | PMID: 31327517
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Abstract

Dimethylarginine dimethylaminohydrolase 1 deficiency aggravates monocrotaline-induced pulmonary oxidative stress, pulmonary arterial hypertension and right heart failure in rats.

Wang D, Li H, Weir EK, Xu Y, Xu D, Chen Y

Patients with pulmonary arterial hypertension (PAH) and right ventricular (RV) failure have a poor clinical outcome, but the mechanisms of PAH and RV failure development are not totally clear. PAH is associated with reduced NO bioavailability and increased endogenous NOS inhibitor asymmetric dimethylarginine (ADMA). Dimethylarginine dimethylaminohydrolase-1 (DDAH1) plays a critical role in ADMA degradation. Here we generated a novel DDAH1 deficiency rat strain using the CRISPR-Cas9 technique, and studied the effect of DDAH1 dysfunction on monocrotaline-induced PAH, lung vascular remodeling and RV hypertrophy. DDAH1 knockout resulted in abolished DDAH1 expression in various tissues, and significant increases of plasma and lung ADMA content. DDAH1 knockout has no detectable effect on cardiac and lung structure, and LV function under control conditions in rats. However, DDAH1 knockout significantly aggravated monocrotaline-induced lung and RV oxidative stress, lung vascular remodeling and fibrosis, pulmonary hypertension and RV hypertrophy in rats. DDAH1 KO resulted in significantly greater increases of plasma and lung ADMA content under control conditions. In the wild type rats monocrotaline resulted in significant increases of plasma and lung ADMA contents and reduction of lung eNOS protein content and these changes were more marked in DDAH1 KO rats. Together, our results demonstrated that DDAH1 plays an important role in attenuating monocrotaline-induced lung oxidative stress, pulmonary hypertension and RV hypertrophy in rats.

Copyright © 2019. Published by Elsevier B.V.

Int J Cardiol: 14 Nov 2019; 295:14-20
Wang D, Li H, Weir EK, Xu Y, Xu D, Chen Y
Int J Cardiol: 14 Nov 2019; 295:14-20 | PMID: 31402164
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Abstract

CMR feature tracking left ventricular strain-rate predicts ventricular tachyarrhythmia, but not deterioration of ventricular function in patients with repaired tetralogy of Fallot.

Hagdorn QAJ, Vos JDL, Beurskens NEG, Gorter TM, ... Berger RMF, Willems TP
Background
Myocardial strain has been shown to predict outcome in various cardiovascular diseases, including congenital heart diseases. The aim of this study was to evaluate the predictive value of cardiac magnetic resonance (CMR) feature-tracking derived strain parameters in repaired tetralogy of Fallot (rTOF) patients for developing ventricular tachycardia (VT) and deterioration of ventricular function.
Methods
Patients with rTOF who underwent CMR investigation were included. Strain and strain-rate of both ventricles were assessed using CMR feature tracking. The primary outcome was a composite of the occurrence of sustained VT or non-sustained VT requiring invasive therapy. The secondary outcome was analyzed in patients that underwent a second CMR after 1.5 to 3.5 years. Deterioration was defined as reduction (≥10%) in right ventricular (RV) ejection fraction, reduction (≥10%) in left ventricular (LV) ejection fraction or increase (≥30 mL/m) in indexed RV end-diastolic volume compared to baseline.
Results
172 patients (median age 24.3 years, 54 patients <18 years) were included. Throughout a median follow-up of 7.4 years, 9 patients (4.5%) experienced the primary endpoint of VT. Multivariate Cox-regression analysis showed that LV systolic circumferential strain-rate was independently predictive of primary outcome (p = 0.023). 70 patients underwent a serial CMR, of whom 14 patients (20%) showed ventricular deterioration. Logistic regression showed no predictive value of strain and strain-rate parameters.
Conclusions
In patients with rTOF, LV systolic circumferential strain-rate is an independent predictor for the development of VT. Ventricular strain parameters did not predict deterioration of ventricular function in the studied population.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Nov 2019; 295:1-6
Hagdorn QAJ, Vos JDL, Beurskens NEG, Gorter TM, ... Berger RMF, Willems TP
Int J Cardiol: 14 Nov 2019; 295:1-6 | PMID: 31402156
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Abstract

Impact of heart rate on coronary computed tomographic angiography interpretability with a third-generation dual-source scanner.

Miller RJH, Eisenberg E, Friedman J, Cheng V, ... Thomson L, Berman DS
Background
Guidelines suggest coronary computed tomography angiography (CCTA) should be performed with a heart rate (HR) below 60. Third-generation dual-source CT (DSCT) scanners, with improved temporal resolution, and end-systolic acquisition may facilitate imaging at higher HRs. We determined the influence of HR and end-systolic acquisition on image interpretability and quality with a third-generation DSCT.
Methods
Patients who underwent CCTA between July 2017 and December 2018 were retrospectively identified. All images were acquired using a SOMATOM Force scanner (Siemens Healthcare). The primary outcome was the presence of any uninterpretable coronary segment. The association between HR and CCTA with uninterpretable segments was assessed with multivariable logistic regression, correcting for demographics and imaging variables.
Results
In total, 2620 patients were included, mean age 61.4 ± 12.9 years and 61.2% male, with uninterpretable segments present in 229 (8.7%) scans. In multivariable analysis, HR 80-89 was associated with an increased likelihood of having a scan with uninterpretable segments (adjusted odds ratio [OR] 4.53, p < 0.001). However, no significant association was present with end-systolic acquisition (HR 80-89, adjusted OR 2.32, p = 0.125). HR ≥ 90 was associated with a decreased likelihood of good or excellent image quality (adjusted OR 0.26, 95% CI 0.11-0.63, p = 0.003).
Conclusions
With third-generation dual-source CT scanners, patients with HR 60-80 can be imaged without impacting image interpretability. End-systolic image acquisition facilitates imaging at HRs > 80 without increasing non-diagnostic scans. Routine use of systolic gating could omit the need for strict HR control and pre-test beta blockade currently required for CCTA.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Nov 2019; 295:42-47
Miller RJH, Eisenberg E, Friedman J, Cheng V, ... Thomson L, Berman DS
Int J Cardiol: 14 Nov 2019; 295:42-47 | PMID: 31427117
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Abstract

Rheumatic fever and rheumatic heart disease: Facts and research progress in Africa.

Muhamed B, Mutithu D, Aremu O, Zühlke L, Sliwa K

In recent years, the devastating effect of rheumatic fever (RF) and rheumatic heart disease (RHD) in Africa has been acknowledged by Institutions such as the Pan-African Society of Cardiology, the African Union Commission, and the World Health Organization. Key priorities set to eradicate RF and RHD include diagnosing and managing RF and RHD, building registries, improving adequate supplies of benzathine penicillin, reproductive health services, and cardiac surgery, developing multi-sectoral RHD awareness programmes, understanding RHD pathogenesis and fostering international partnership for resource mobilization. There were volumes of peer reviewed publications focusing on the key priorities to fight RHD in different parts to Africa; both individually as well as through international collaborations. This article analyzed findings and reports from 1961 to 2018 on efforts to eradicate RF and RHD in Africa.

Copyright © 2019. Published by Elsevier B.V.

Int J Cardiol: 14 Nov 2019; 295:48-55
Muhamed B, Mutithu D, Aremu O, Zühlke L, Sliwa K
Int J Cardiol: 14 Nov 2019; 295:48-55 | PMID: 31405583
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Abstract

Incidental abnormal ECG findings and long-term cardiovascular morbidity and all-cause mortality: A population based prospective study.

Goldman A, Hod H, Chetrit A, Dankner R
Background
The additional prognostic value of resting electrocardiogram (ECG) in long-term cardiovascular disease (CVD)-risk-assessment is unclear. We evaluated the association of incidental abnormal ECG findings with long-term CVD-risk and all-cause mortality, and assessed the additional prognostic value of ECG as a screening tool in adults without known CVD.
Methods
A cohort of 2601 Israeli men and women without known CVD were actively followed from 1976 to 1982 for 23-year cumulative CVD-incidence, and until May 2017 for all-cause mortality. At baseline and follow-up, participants underwent interviews, physical examinations, blood tests and ECG.
Results
At baseline, 1199 (46.1%) had incidental abnormal ECG findings (exposed-group). CVD cumulative incidence reached 31.6% among the 930 survivors who participated in the active follow-up (294/930). During a 31-year median follow-up, 1719 (66.1%) of the total cohort died. Incidental abnormal ECG findings were associated with 46% greater CVD-risk (odds ratio = 1.46, 95%CI = 1.09-1.97). The net reclassification improvement (NRI) of CVD-risk was 7.4% (95%CI = 1.5%-13.3%, p = 0.01) following the addition of ECG findings, but the C-index improvement was not statistically significant [C-index = 0.656 (0.619-0.694) vs. C-index = 0.666 (0.629-0.703), p = 0.14]. Multivariable Cox regression demonstrated an all-cause mortality hazard ratio (HR) of 1.18 (95%CI = 1.07-1.30) for exposed vs. unexposed individuals. Non-specific T-wave changes and left-axis deviation are the incidental ECG abnormalities that were associated with all-cause mortality [HR = 1.18 (95%CI = 1.05-1.33) and HR = 1.19 (95%CI = 1.00-1.42), respectively].
Conclusion
Incidental abnormal ECG findings, mainly non-specific T-wave changes and left-axis deviation, were associated with increased long-term CVD-risk and all-cause mortality among individuals without known CVD, and demonstrated net reclassification improvement for CVD-risk.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Nov 2019; 295:36-41
Goldman A, Hod H, Chetrit A, Dankner R
Int J Cardiol: 14 Nov 2019; 295:36-41 | PMID: 31412991
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Abstract

Sarcopenia is common in adults with complex congenital heart disease.

Sandberg C, Johansson K, Christersson C, Hlebowicz J, Thilén U, Johansson B
Background
Adults with complex congenital heart disease (CHD) have reduced aerobic capacity and impaired muscle function. We therefore hypothesized that patients have a lower skeletal muscle mass and higher fat mass than controls.
Methods
Body composition was examined with full body Dual-Energy x-ray Absorptiometry (DXA) in 73 patients with complex CHD (mean age 35.8 ± 14.3, women n = 22) and 73 age and sex matched controls. Patients fulfilling criteria for low skeletal muscle mass in relation to their height and fat mass were defined as sarcopenic.
Results
Male patients (n = 51) were shorter (177.4 ± 6.6 cm vs. 180.9 ± 6.7 cm, p = 0.009) and weighed less (76.0 ± 10.8 kg vs. 82.0 ± 12.4 kg, p = 0.01) than controls. Also, patients had a lower appendicular lean mass-index (ALM-index) (7.57 ± 0.97 kg/mvs. 8.46 ± 0.90 kg/m, p < 0.001). Patients\' relative tissue fat mass (27.9 ± 7.0% vs. 25.4 ± 8.6%, p = 0.1) did not differ. Forty-seven percent of the men (n = 24) were classified as sarcopenic. Female patients (n = 22) were also shorter (163.5 ± 8.7 cm vs. 166.7 ± 5.9 cm, p = 0.05) but had a higher BMI (25.7 ± 4.2 vs. 23.0 ± 2.5, p = 0.02) than controls. Patients also had a lower ALM-index (6.30 ± 0.75 vs. 6.67 ± 0.55, p = 0.05), but their relative body fat mass (40.8 ± 7.6% vs. 32.0 ± 7.0%, p < 0.001) were higher. Fifty-nine percent of the women (n = 13) were classified as sarcopenic.
Conclusions
The body composition was altered toward lower skeletal muscle mass in patients with complex CHD. Approximately half of the patients were classified as sarcopenic. Contrary to men, the women had increased body fat and a higher BMI. Further research is required to assess the cause, possible adverse long-term effects and whether sarcopenia is preventable or treatable.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:57-62
Sandberg C, Johansson K, Christersson C, Hlebowicz J, Thilén U, Johansson B
Int J Cardiol: 30 Nov 2019; 296:57-62 | PMID: 31230936
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Abstract

Lipid levels achieved after a first myocardial infarction and the prediction of recurrent atherosclerotic cardiovascular disease.

Ohm J, Hjemdahl P, Skoglund PH, Discacciati A, ... Jernberg T, Svensson P
Background
Low density lipoprotein cholesterol (LDL-C) goals post-myocardial infarction (MI) are debated, and the significance of achieved blood lipid levels for predicting a first recurrent atherosclerotic cardiovascular disease (rASCVD) event post-MI is unclear.
Methods
This was a cohort study on first-ever MI survivors aged ≤76 years attending 4-14 week revisits throughout Sweden 2005-2013. Personal-level data was collected from SWEDEHEART and linked national registries. Exposures were quintiles of LDL-C, high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TGs) at the revisit. Group level associations with rASCVD (nonfatal MI or coronary heart disease death or fatal or nonfatal ischemic stroke) were estimated in Cox regression models. Predictive capacity was estimated by differences in C-statistic, integrated discriminatory improvement, and net reclassification improvement when adding each blood lipid to a validated risk prediction model.
Results
25,643 patients, 96.9% on statin therapy, were followed during a mean of 4.1 years. rASCVD occurred in 2173 patients (8.5%). For LDL-C and TC, moderate associations with rASCVD were observed only in the 5th vs. the lowest (referent) quintiles. For TGs and HDL-C increased risks were observed in quintiles 3-5 vs. the lowest. Minor predictive improvements were observed when lipid fractions were added to the risk model but the discrimination overall was poor (C-statistics <0.6).
Conclusions
Our data question the importance of LDL-C levels achieved at first revisit post-MI for decisions on continued treatment intensity considering the weak association with rASCVD observed in this post-MI cohort.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:1-7
Ohm J, Hjemdahl P, Skoglund PH, Discacciati A, ... Jernberg T, Svensson P
Int J Cardiol: 30 Nov 2019; 296:1-7 | PMID: 31303394
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Abstract

ACUTE HF score, a multiparametric prognostic tool for acute heart failure: A real-life study.

Cameli M, Pastore MC, De Carli G, Henein MY, ... Valente S, Mondillo S
Background
Acute heart failure (AHF) is the first cause of hospitalization for over-65 individuals, associated with high mortality and readmission rate. The aim of this study was to assess the prognostic value of a multiparametric score combining clinical, biochemical and echocardiographic indexes in AHF for clinical practice.
Methods
830 patients hospitalized for AHF were enrolled. Exclusion criteria were: active neoplasms; previous heart transplantation or left ventricular assist device implantation. Different variables were analyzed: etiology of AHF, clinical and biochemical data, lung congestion on chest-X ray, echocardiographic parameters and administered therapy. The endpoints were: all-cause mortality at 30 days, 6 months and 5 years and the duration of hospitalization.
Results
771 patients met eligibility criteria. Using the univariate and multivariate analysis the indexes with the best correlation with outcome were discretized and used to create the ACUTE HF score, computed as: 1.4*[serum creatinine>2 mg/dl] + 0.8*[ejection fraction<30] + 0.7*[age > 76] + 0.7*[prior hospitalization for AHF] + 0.9*[prior stroke/transient ischemic attack] + 0.5*[more than moderate mitral regurgitation] + 0.8*[use of non-invasive ventilation] and used to divide patients into 3 groups according to the risk of 6-months mortality. With the receiver operating curves and Kaplan-Meier analysis, this score proved to have a high predictive power for mortality at 30 days, 6 months and 5 years from hospitalization, and for event-free survival rates, providing a risk stratification capability superior to that of single variables.
Conclusions
The ACUTE HF score could be a complete and useful tool for assessing prognosis of AHF patients. It could represent a step in the long standardization pathway of prognostic protocols for AHF.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:103-108
Cameli M, Pastore MC, De Carli G, Henein MY, ... Valente S, Mondillo S
Int J Cardiol: 30 Nov 2019; 296:103-108 | PMID: 31324396
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Abstract

Managed Care after Acute Myocardial Infarction (MC-AMI) - a Poland\'s nationwide program of comprehensive post-MI care - improves prognosis in 12-month follow-up. Preliminary experience from a single high-volume center.

Wita K, Wilkosz K, Wita M, Kułach A, ... Turski M, Szydło K
Background
Despite progress in the treatment of acute myocardial infarction (AMI), long-term prognosis in MI survivors remains a challenge. The Managed Care in Acute Myocardial Infarction (MC-AMI, KOS-zawal) is the first program of a comprehensive, supervised care for patients with AMI to improve long-term prognosis. It includes acute intervention, complex revascularization, cardiac rehabilitation (CR), outpatient follow-up, and prevention of SCD. Our aim was to assess the relation between participation in MC-AMI and major adverse cardiovascular and cerebrovascular events (MACCE) in 12-month follow-up.
Methods and results
In this single-center, retrospective analysis we compared 719 patients participating in MC-AMI and compared them to 1130 subjects in the control group. After propensity score matching, two groups of 529 subjects each were compared. MC-AMI was related with MACCE reduction by 40% in a 12-month observation. Participants of MC-AMI had a higher adherence to cardiac rehabilitation (98 vs. 14%), higher rate of scheduled revascularisation (coronary artery bypass grafting: 9.8% vs. 4.9%, p ≪ 0.001; elective percutaneous coronary intervention: 3.0% vs 2.1%, p ≪ 0.05) and ICD implantation (2.8% vs. 0.6%, p ≪ 0.05) compared to control. Multivariable Cox regression analysis revealed MC-AMI to be inversely associated with the occurrence of MACCE (HR = 0.500, 95% Cl 0.349-0.718, p ≪ 0.001). Besides, older age, diabetes mellitus, hyperlipidemia, prior PAD, previous UA, and lower LVEF were significantly associated with the primary endpoint.
Conclusions
MC-AMI is the first program of comprehensive care for AMI patients. MC-AMI improves prognosis by increasing the rate of patients undergoing CR, complete revascularization and ICD implantation, thus reducing MACCE.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:8-14
Wita K, Wilkosz K, Wita M, Kułach A, ... Turski M, Szydło K
Int J Cardiol: 30 Nov 2019; 296:8-14 | PMID: 31256995
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Impact:
Abstract

Exposure to second hand smoke and 10-year (2002-2012) incidence of cardiovascular disease in never smokers: The ATTICA cohort study.

Critselis E, Panagiotakos DB, Georgousopoulou EN, Katsaounou P, ... Pitsavos C,
Background
Despite WHO Framework Convention of Tobacco Control (FCTC) adoption, effective implementation of national smoking bans remains pending in several countries. This study quantified the association of second hand smoke (SHS) exposure and 10-year cardiovascular disease (CVD) among never smokers in such settings.
Methods
In 2001-2002, a sample of 1514 males and 1528 females (range: 18-89 years old) were randomly selected in Greece. Frequency and duration of SHS exposure (i.e. exposure extending >30 min/day) within the home and/or workplace were assessed by interview. Following a 10-year follow-up period (2002-2012), incidence of non-fatal and fatal CVD (ICD-10) was evaluated among n = 2020 participants. The analytic study sample consisted of all never smokers (n = 910).
Results
Despite national smoking ban implementation (2009), 44.6% (n = 406) of never smokers reported SHS exposure. While SHS exposed never smokers exhibited a more favorable profile of CVD-related risk factors at baseline, they subsequently developed similar 10-year CVD incidence rates, at a younger mean age (p = 0.001), than their non-exposed counterparts. Following adjustment for several lifestyle and clinical factors, SHS exposed never smokers exhibited a two-fold elevated 10-year CVD risk (adj. HR: 2.04, 95% CI: 1.43-2.92), particularly among women (adj. HR: 2.45, 95% CI: 1.45-4.06). SHS exposure accounted for 32% excess Population Attributable Risk (PAR) for 10-year CVD events in never smokers, with highest rates (PAR: 52%) being among those exposed in the workplace.
Conclusion
The prevention of SHS associated CVD and related healthcare costs mandates additional strategies for securing the effective implementation of comprehensive WHO FCTC based national smoking bans.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Nov 2019; 295:29-35
Critselis E, Panagiotakos DB, Georgousopoulou EN, Katsaounou P, ... Pitsavos C,
Int J Cardiol: 14 Nov 2019; 295:29-35 | PMID: 31375335
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Impact:
Abstract

Diagnosis of immune checkpoint inhibitor-associated myocarditis: A systematic review.

Pradhan R, Nautiyal A, Singh S
Background
Myocarditis is a rare but severe adverse event associated with immune checkpoint inhibitors, its diagnosis depending on a high index of suspicion and appropriate investigations. Our objective was to systematically review the diagnostic approaches to myocarditis associated with immune checkpoint inhibitors.
Methods
The systematic review was conducted according to the PRISMA guidelines (PROSPERO Registration: CRD42018097247). We searched Medline and Embase for case reports, case series, and observational studies published in journal articles or presented as conference abstracts that describe patients who developed myocarditis after immune checkpoint inhibitor therapy.
Results
After a review of 2326 citations, we included 88 cases (53 case reports/series published in journal articles and 35 cases in the observational study). Serum troponin was elevated in 98% of the case reports and 94% of participants in the observational study. ST changes including ST elevation were present in almost a third of case reports. Echocardiography revealed preserved left ventricular ejection fraction in 32% of case reports and 51% of cases in the observational study; however, preserved systolic function did not predict greater survival. Patients who suffered poorer prognosis tended to have major conduction defects or ventricular arrhythmias more frequently than patients who did not. Acute myocardial ischemia was ruled out in all cases (n = 31) when the diagnostic workup included coronary angiography.
Conclusions
Immune checkpoint inhibitor-associated myocarditis is characterized by elevation of cardiac troponin levels and non-specific electrocardiographic changes. Early coronary angiography may distinguish it from myocardial ischemia or myocardial infarction.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:113-121
Pradhan R, Nautiyal A, Singh S
Int J Cardiol: 30 Nov 2019; 296:113-121 | PMID: 31327516
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Impact:
Abstract

Cardiac troponin elevations in marathon runners. Role of coronary atherosclerosis and skeletal muscle injury. The MaraCat Study.

Paana T, Jaakkola S, Bamberg K, Saraste A, ... Pettersson K, Airaksinen KEJ
Background
Marathon running is associated with transient risk of sudden cardiac death and high cardiac troponin levels are common after race. There is limited data whether coronary atherosclerosis or skeletal muscle injury are related to troponin release caused by strenuous exercise. We aimed to assess whether coronary artery calcification (CAC), plaque vulnerability or skeletal muscle injury relate to cardiac troponin T (cTnT) elevations after marathon race.
Methods
In this observational study, 40 male runners participating in Paavo Nurmi 2018 Marathon were recruited with an open email invitation to evaluate the prevalence of post-race cTnT elevations and their predictors. In addition to baseline and post-race laboratory investigations, 28 runners aged >44 years underwent CAC measurement with computed tomography. Coronary plaque vulnerability was evaluated by free pregnancy-associated plasma protein A (fPAPP-A) concentration and skeletal muscle injury by skeletal troponin I (skTnI) measurement.
Results
The post-marathon cTnT concentrations rose above the normal reference limit in 38 (95%) participants. A 10-fold increase in skTnI concentrations was observed and elevated post-race values were seen in all participants. The correlation between the post-race cTnT and post-race skTnI (r = -0.26, p = 0.11) was non-significant. CAC was detected (Agatston score > 0) in 15 (53.6%) participants, with a median score of 2.0 (interquartile range [IQR] 80). There was no correlation between cTnT with CAC score or post-race fPAPP-A levels.
Conclusions
Asymptomatic cardiac troponin elevations are common after prolonged strenuous exercise, but are not related to markers of coronary atherosclerosis, plaque vulnerability or skeletal muscle injury.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Nov 2019; 295:25-28
Paana T, Jaakkola S, Bamberg K, Saraste A, ... Pettersson K, Airaksinen KEJ
Int J Cardiol: 14 Nov 2019; 295:25-28 | PMID: 31420104
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Impact:
Abstract

Prognostic value of cardiac metaiodobenzylguanidine imaging and QRS duration in implantable cardioverter defibrillator patients with and without heart failure.

Kawasaki M, Yamada T, Morita T, Furukawa Y, ... Sakata Y, Fukunami M
Background
Cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with heart failure (HF). Recent studies showed that the highest rate of ventricular tachyarrhythmias (VTs) is seen in HF patients with an intermediate decrease in MIBG uptake, rather than in those with the lowest values. However, prolonged QRS duration (QRSd) has been shown to be associated with VTs in HF patients. This study assessed the prognostic value of the combination of an intermediate decrease in MIBG uptake and prolonged QRSd for predicting VTs in patients with implantable cardioverter defibrillators (ICDs) in relation to the presence of heart failure (HF).
Methods and results
A total of 196 outpatients with ICDs (age: 64 ± 14 years, male: 81%, left ventricular ejection fraction [LVEF]: 49% ± 16%) were prospectively enrolled; 135 had HF (NYHA class: 2.0 ± 0.6). At entry, cardiac MIBG imaging was performed, and QRSd was measured on standard 12‑lead electrocardiography. An intermediate decrease in the heart-to-mediastinum ratio on the delayed planar image (ID-H/M) was defined as 1.40-1.89. During the 3.3 ± 2.2-year follow-up, 59 patients had appropriate ICD discharges (ATx) for VTs. On multivariate Cox analysis, ID-H/M and prolonged QRSd (≥147 ms) were significantly and independently associated with ATx. In both patients with and without HF, ATx were significantly more frequent in patients with ID-H/M and/or prolonged QRSd than in those with neither (with HF: 40% vs. 14%, p = 0.020; without HF: 43% vs. 10%, p = 0.0028).
Conclusions
The combination of ID-H/M and prolonged QRSd provided more prognostic information for predicting VTs in ICD patients, with and without HF.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:164-171
Kawasaki M, Yamada T, Morita T, Furukawa Y, ... Sakata Y, Fukunami M
Int J Cardiol: 30 Nov 2019; 296:164-171 | PMID: 31371118
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Impact:
Abstract

Oral anticoagulation for subclinical atrial tachyarrhythmias detected by implantable cardiac devices: an international survey of the AF-SCREEN Group.

Boriani G, Healey JS, Schnabel RB, Lopes RD, ... Camm JA, Freedman B
Aims
At present, there is little evidence on how to treat subclinical atrial fibrillation (SCAF) or atrial high rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs). Our aim was to assess current practice around oral anticoagulation (OAC) in such patients.
Methods
A web-based survey undertaken by 310 physicians: 59 AF-SCREEN International Collaboration members and 251 non-members.
Results
In patients with SCAF/AHRE and a CHADSVASc ≥ 2 in males or ≥ 3 in female the amount of SCAF/AHRE triggering use of OAC was variable but <2% of respondents considered that no AHRE would require OAC. Around one third (34%) considered SCAF/AHRE duration of >5-6 min as the basis for OAC prescription, while 16% and 18% required a burden of at least 5.5 h or 24 h, respectively. The propensity to prescribe OAC for a low burden of AHREs differed according to certain respondent characteristics (greater propensity to prescribe OAC for neurologists). When the clinical scenario included a prior stroke or a prior cardioembolic stroke, stated prescription of OAC was very high. More than 96% felt that any SCAF/AHRE should be treated with OAC.
Conclusions
There is substantial heterogeneity in the perception of the risk of stroke/systemic embolism associated with SCAF/AHRE of variable duration. The threshold of AHRE burden that would trigger initiation of OAC is highly variable, and differs according to the clinical scenario (lower threshold in case of previous stroke). Ongoing trials will clarify the real benefit and risk/benefit ratio of OAC in this specific clinical setting.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:65-70
Boriani G, Healey JS, Schnabel RB, Lopes RD, ... Camm JA, Freedman B
Int J Cardiol: 30 Nov 2019; 296:65-70 | PMID: 31327519
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Impact:
Abstract

Significance of the CAPRI risk score to predict heart failure hospitalization post-TAVI: The CAPRI-HF study.

Harbaoui B, Durand E, Dupré M, Rabilloud M, ... Eltchaninoff H, Lantelme P
Background
Predictors of heart failure (HF) hospitalization after transcatheter aortic valve implantation (TAVI) are not well defined. CAPRI is a score for predicting 1-year post-TAVI cardiovascular and all-cause mortality. The aim of the present study is to assess the prognostic significance of the CAPRI score for HF hospitalization 1 year after TAVI.
Methods and results
CAPRI-HF is an ancillary study of the C4CAPRI trial, analyzing 409 consecutive patients treated by TAVI. The primary outcome was hospitalization for HF during the first year post-intervention. The prognostic value of the CAPRI score was assessed by multivariable analysis adjusted for diabetes, atrial fibrillation, vascular route, pacemaker implantation, post-TAVI aortic regurgitation, transfusion and pulmonary artery systolic pressure. A subanalysis focused on patients with low-gradient aortic stenosis (LGAS). At 1 year, HF hospitalization occurred in 78 (19.9%) patients. Patients with HF were more prone to have diabetes, atrial fibrillation, renal dysfunction, lower mean aortic gradient, higher logistic EuroSCORE and higher CAPRI score (p < .05 for all associations). In the multivariable analysis, CAPRI score was the sole predictor of HF: hazard ratio (HR) for each 0.1 CAPRI score increase was 1.065, 95% confidence interval (CI) 1.021-1.110. This was confirmed when adjusted for EuroSCORE: HR 1.066, 95% CI 1.024-1.110. The predictive power of the CAPRI score increased for LGAS: HR 1.098, 95% CI 1.028-1.172.
Conclusions
CAPRI score helps predict HF post-TAVI. Including the score in the decision-making process may help selecting candidates for TAVI and identifying patients who need close monitoring post-procedure.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:98-102
Harbaoui B, Durand E, Dupré M, Rabilloud M, ... Eltchaninoff H, Lantelme P
Int J Cardiol: 30 Nov 2019; 296:98-102 | PMID: 31455517
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Impact:
Abstract

False-positive stress echocardiograms: Predictors and prognostic relevance.

Rachwan RJ, Mshelbwala FS, Dardari Z, Batal O
Background
Recent studies indicate that the pretest likelihood of significant coronary artery disease (CAD) (≥50% luminal stenosis) is over-estimated and that the frequency and severity of positive stress tests have been decreasing. This suggests an increased prevalence of false-positive (FP) stress tests. The aims of this retrospective study were to investigate the predictors of FP stress echocardiography (SE) and to compare the outcomes of patients with FP results to those with true-positive (TP) results.
Methods
Patients who underwent SE between 2013 and 2017 in a tertiary-care center were reviewed. Included were patients aged ≥40years who had cardiac catheterization (CC) within 1year of the index stress test. SE was considered FP if a new or worsening wall motion abnormality was present in the absence of significant corresponding CAD.
Results
Of the 5100 patients with SE, 1069 satisfied inclusion criteria. A total of 305 patients had positive SE results; of which 162 (53%) were FP. Logistic regression revealed that female gender (p=0.009), the absence of diabetes (p=0.03), the absence of a personal history of CAD (p=0.004), and lower stress WMSI (p=0.03) were independently associated with FP results. Patients with FP results on SE had similar all-cause mortality to those with TP results.
Conclusions
Accounting for predictors of FP findings on SE could improve the interpretation of SE results and limit the use of unnecessary CC. Furthermore, patients with FP results on SE could benefit from aggressive risk factor control and careful clinical follow-up.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:157-163
Rachwan RJ, Mshelbwala FS, Dardari Z, Batal O
Int J Cardiol: 30 Nov 2019; 296:157-163 | PMID: 31477317
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Impact:
Abstract

Loss of Rubicon ameliorates doxorubicin-induced cardiotoxicity through enhancement of mitochondrial quality.

Liu X, Zhang S, An L, Wu J, ... He L, Zhu H
Background
The therapeutic potential of doxorubicin (DOX) is limited by cardiotoxicity. Rubicon is an inhibitory interacting partner of autophagy protein UVRAG. Currently, the role of Rubicon in DOX-induced cardiotoxicity is unknown. In this study, we test the hypothesis that loss of Rubicon attenuates DOX-induced cardiotoxicity.
Methods
A mouse model of acute DOX-induced cardiotoxicity was established by a single intraperitoneal injection of DOX at a dose of 20 mg/kg. Rubicon expression was detected by Western blot. Cardiac damage was determined by measuring activities of lactate dehydrogenase and myocardial muscle creatine kinase in the serum, cytoplasmic vacuolization, collagen deposition, ROS levels, ATP content and mitochondrial damage in the heart. Cardiac morphometry and function were assessed by echocardiography. Markers for autophagy, mitophagy and mitochondrial dynamics were evaluated by Western blot and real time reverse transcription polymerase chain reaction.
Results
Rubicon expression was reduced in the heart 16 h after DOX treatment. DOX induced accumulation of cytoplasmic vacuolization and collagen, increased serum activities of lactate dehydrogenase and myocardial muscle creatine kinase, enhanced ROS levels, reduced ATP content, pronounced mitochondrial damage and greater left ventricular wall thickness in wild type mice, which were mitigated by Rubicon deficiency. Mechanistically, loss of Rubicon improved DOX-induced impairment of autophagic flux, Parkin-mediated mitophagy and mitochondrial fission and fusion in the heart.
Conclusions
Loss of Rubicon ameliorates DOX-induced cardiotoxicity through enhancement of mitochondrial quality by improving autophagic flux, mitophagy and mitochondrial dynamics. Rubicon is a potential molecular target for prevention and therapy of DOX cardiotoxicity.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:129-135
Liu X, Zhang S, An L, Wu J, ... He L, Zhu H
Int J Cardiol: 30 Nov 2019; 296:129-135 | PMID: 31439425
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Impact:
Abstract

Gene therapy for atrial fibrillation - How close to clinical implementation?

Trivedi A, Hoffman J, Arora R

In this review we examine the current state of gene therapy for the treatment of cardiac arrhythmias. We describe advances and challenges in successfully creating and incorporating gene vectors into the myocardium. After summarizing the current scientific research in gene transfer technology we then focus on the most promising areas of gene therapy, the treatment of atrial fibrillation and ventricular tachyarrhythmias. We review the scientific literature to determine how gene therapy could potentially be used to treat patients with cardiac arrhythmias.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:177-183
Trivedi A, Hoffman J, Arora R
Int J Cardiol: 30 Nov 2019; 296:177-183 | PMID: 31439427
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Impact:
Abstract

Sympathetic and renin-angiotensin-aldosterone system activation in heart failure with preserved, mid-range and reduced ejection fraction.

Vergaro G, Aimo A, Prontera C, Ghionzoli N, ... Passino C, Emdin M
Background
Evidence of sympathetic and renin-angiotensin-aldosterone system activation provided a rationale for neurohormonal antagonism in heart failure with reduced ejection fraction (HFrEF), while no data are available in patients with milder degree of systolic dysfunction. We aimed to investigate neurohormonal function in HF with preserved and mid-range EF (HFpEF/HFmrEF).
Methods
Three cohorts (n = 189/each) of stable HFpEF, HFmrEF and HFrEF patients were selected (median age 70, 67 and 67 years; male 56%, 73% and 74%, respectively). Patients received a baseline clinical assessment including plasma renin activity (PRA), aldosterone, catecholamines, and N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) assays, and were followed-up for all-cause death.
Results
Neuroendocrine profile was similar between HFpEF and HFmrEF, while all neurohormones except epinephrine were higher in HFrEF than in HFmrEF (NT-proBNP 2332 ng/L, IQR 995-5666 vs 575 ng/L, 205-1714; PRA 1.7 ng/mL/h, 0.4-5.6 vs 0.6 ng/mL/h, 0.2-2.6; aldosterone 153 ng/L, 85-246 vs 113 ng/L, 72-177; norepinephrine 517 ng/L, 343-844 vs 430 ng/L, 259-624; all p < 0.001, epinephrine 31 ng/L, 10-63 vs 25 ng/L, 10-44; p = 0.319). These findings were unrelated to treatment heterogeneity. Ten percent of HFpEF patients had elevated PRA, aldosterone and norepinephrine vs. 8% in HFmrEF and 21% in HFrEF. During a 5-year follow-up, survival decreased with the number of neurohormones elevated (HFpEF: log-rank 7.8, p = 0.048; HFmrEF: log-rank 11.8, p = 0.008; HFrEF: log-rank 8.1, p = 0.044).
Conclusions
Neurohormonal activation is present only in a subset of patients with HFpEF and HFmrEF, and may hold clinical significance. Neurohormonal antagonism may be useful in selected HFpEF/HFmrEF population.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:91-97
Vergaro G, Aimo A, Prontera C, Ghionzoli N, ... Passino C, Emdin M
Int J Cardiol: 30 Nov 2019; 296:91-97 | PMID: 31443984
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Impact:
Abstract

Cardiovascular Disease and hospital admissions in African immigrants and former Soviet Union immigrants: A retrospective cohort study.

Reuven Y, Shvartzman P, Dreiher J
Background
Previous studies reported low prevalence of cardiovascular disease (CVD) despite an increasing prevalence of metabolic abnormalities in immigrants who moved from low CVD-risk regions to Western countries. Nevertheless, little is known about hospital admissions due to CVD in immigrants.
Methods
A retrospective cohort study of East Africa immigrants (EAI), Former Soviet Union immigrants (FSUI) and native-born Israelis (NBI) over 11-year period. Associations between ethnicity, age, sex, CVD, and hospital admission were assessed using logistic and Poisson regression models. Incidence density rates per person-years were calculated.
Results
The age-adjusted prevalence rates of ischemic heart disease in EAI, FSUI and NBI, respectively, were 1.8%, 8.2%, and 5.8%, respectively (p < 0.001). The corresponding rates for stroke were 2.6%, 3.5%, and 2.5%, respectively. Multivariate odds ratios for all CVD were found to be significantly lower in EAI for both sexes. Hospitalizations rate due to CVD were 9, 17, and 6 per 1000 person-years in EAI, FSUI and NBI, respectively (p < 0.001). EAI were more likely to be hospitalized due to hypertensive disease, cerebral vascular diseases and heart disease, in comparison to NBI and FSUI. However, when controlling for CVD risk factors profile, EAI had similar admission rates to NBI. EAI were more likely to be hospitalized in internal medicine, geriatrics, and neurology departments, and less likely to be admitted to intensive care units or surgical department.
Conclusions
EAI had low rates of all types of CVD, and low risk of hospitalization after controlling for CVD risk factors profile.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:172-176
Reuven Y, Shvartzman P, Dreiher J
Int J Cardiol: 30 Nov 2019; 296:172-176 | PMID: 31477314
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Impact:
Abstract

Usefulness of dual imaging stress echocardiography for the diagnosis of coronary allograft vasculopathy in heart transplant recipients.

Pichel IÁ, Fernández Cimadevilla OC, de la Hera Galarza JM, Pasanisi E, ... Sicari R, Fernández MM
Background
Coronary allograft vasculopathy (CAV) is the main factor limiting long-term survival after cardiac transplantation. Dual imaging stress echocardiography with wall motion and Doppler-derived coronary flow reserve (CRF) of the left anterior descending artery (LAD) is a state-of-the-art methodology during dipyridamole stress echocardiography (DiSE). This study involving 74 heart transplanted patients has the purpose to assess the diagnostic value of dipyridamole stress echocardiography with evaluation of wall motion (WM) and Doppler-derived coronary flow reserve for the diagnosis of coronary allograft vasculopathy.
Methods and results
All patients underwent DiSE and coronary angiography. Moderate-severe CAV was defined according to International Society of Heart and Lung Transplant (ISHLT) recommended nomenclature for CAV, and CFR < 2 was considered to be impaired. Moderate-severe CAV was present in 11 patients. WM analysis revealed four patients (5%) with rest WM abnormalities. CFR analysis revealed that 40 (54%) individuals had an abnormal result. The combined evaluation of WM analysis and CFR resulted in a sensitivity of 72.7% (95% CI: 39.3 to 92.6%), a specificity of 49.2% (95% CI: 36.5 to 61.9%), a positive predictive value of 20% (95% CI: 9.6 to 36.1%), and negative predictive value of 91.1% (95% CI: 75.1 to 97.6%) for the diagnosis of CAV.
Conclusions
Our results support the inclusion of DiSE performance in Heart transplant follow up protocol. The addition of CFR evaluation offers valuable information to the angiography findings in the detection of CAV and could be helpful in selected patients to adjust the time and indications of coronary angiography.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:109-112
Pichel IÁ, Fernández Cimadevilla OC, de la Hera Galarza JM, Pasanisi E, ... Sicari R, Fernández MM
Int J Cardiol: 30 Nov 2019; 296:109-112 | PMID: 31324395
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Impact:
Abstract

The age-related blood pressure trajectories from young-old adults to centenarians: A cohort study.

Wang R, Vetrano DL, Liang Y, Qiu C
Background
Blood pressure (BP) trajectories among older adults, especially among the oldest-old, are still poorly characterized.
Objective
To investigate the longitudinal trajectories of four BP components with age and their potential influential factors.
Methods
This population-based prospective cohort study included 3315 participants (age 60-105 years, 64.6% women) who were regularly examined from 2001 to 2004 through 2013-2016. The longitudinal trajectories of systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP) with age were estimated using linear mixed-effects models.
Results
Overall, SBP and PP increased with age until ∼80 years and then declined, whereas DBP and MAP decreased constantly after 60 years of age. The age-related BP trajectories varied by survival time, birth cohort, use of antihypertensive drugs, and heart disease. Specifically, people who survived <2 years after the last visit showed higher levels of BP components before ∼80 years, followed by steeper declines in SBP and PP. At the same age, people who were born earlier showed higher BP than those who were born later. People who used antihypertensive drugs had higher BP than those who did not until ∼80-90 years old, thereafter BP showed no significant difference. After ∼80 years old, people with heart disease showed steeper declines in SBP and PP than those without.
Conclusions
The late-life longitudinal BP trajectories with age vary with demographics, clinical conditions, and contextual factors. These findings may help better understand the age-dependent relationship of BP with health outcomes as well as help achieve optimal BP control in older people.
Perspectives
Competency in medical knowledge: Understanding the age-related blood pressure trajectories and potential influential factors may help improve blood pressure management in older people. Translational outlook 1: Blood pressure trajectories with age in older adults vary by birth cohort, survival time, antihypertensive therapy, and heart disease. The age-related blood pressure trajectories by birth cohorts are featured with lower blood pressure levels at the same age in more recent birth cohorts, which may partially reflect the improvement of blood pressure control over time. Translational outlook 2: The age-related blood pressure trajectories in the oldest old (e.g., age ≥ 85 years) are characterized by steeper and faster blood pressure declines associated with heart disease and short survival (e.g., <2 years). This may have implications for the optimal management of blood pressure as well as for the interpretation of the relationships between blood pressure and health outcomes (e.g., death) among the oldest old.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:141-148
Wang R, Vetrano DL, Liang Y, Qiu C
Int J Cardiol: 30 Nov 2019; 296:141-148 | PMID: 31443986
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Impact:
Abstract

Circular RNA expression alterations in extracellular vesicles isolated from murine heart post ischemia/reperfusion injury.

Ge X, Meng Q, Zhuang R, Yuan D, ... Fan H, Zhou X
Background
Increasing studies indicated the involvement of extracellular vesicles (EVs) in cardiovascular diseases. However, the role of circular RNAs (circRNAs) in cardiac EVs (cEVs) during ischemia/reperfusion (I/R) injury remain unclear.
Methods
We isolated the cEVs from I/R injured hearts and performed RNA sequencing (RNA-seq) to identify the profile of circRNA in cEVs and investigated their potential roles in I/R pathological process.
Results
Cardiac I/R induced a significantly elevated release of EVs in heart within 24 h. RNA-seq of cEVs identified 185 significantly differentially expressed (DE) circRNAs including 119 down-regulated and 66 up-regulated circRNAs in I/R group compared with the sham. GO and pathway analysis showed that these DE-circRNAs were associated with protein binding and kinase activator activity and mainly involved in the metabolic process. The circRNA-miRNA analysis exhibited the broad potentials of the DE-circRNAs to regulate target genes by acting on the miRNAs.
Conclusions
These findings revealed for the first time the specific expression pattern of circRNAs in EVs derived from sham and I/R heart tissues and provided some potential targets and pathways involving in I/R injury which may provide important evidences for the role of both circRNA and EVs in the pathology of cardiac I/R.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:136-140
Ge X, Meng Q, Zhuang R, Yuan D, ... Fan H, Zhou X
Int J Cardiol: 30 Nov 2019; 296:136-140 | PMID: 31466885
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Impact:
Abstract

Late clinical outcomes of unselected patients with diabetic mellitus and multi-vessel coronary artery disease.

Ebrahim MEBM, Dignan R, Femia G, Kim S, ... Juergens CP, French JK
Background
The Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multi-Vessel Disease (FREEDOM) clinical trial randomized only a proportion of screened patients with diabetes mellitus (DM) and multi-vessel disease (MVD).
Methods and results
We determined late rates of death, non-fatal myocardial infarction (MI) and stroke in all 430 patients with DM who had MVD identified on angiographic screening for the FREEDOM Trial, which recruited from June 2006 -March 2010 at Liverpool Hospital, Sydney, Australia. Mortality at 6 years [median] was 23% among 192 FREEDOM-eligible patients and 26% among 238 FREEDOM-ineligible patients, of whom 139 [58%] had prior. CABG (mortality 31%). Overall, 196 (45%) had percutaneous coronary intervention (PCI), 127 (30%) underwent coronary artery bypass grafting (CABG) (who were 4 years younger; p = 0.003), and 107 (25%) had neither procedure of whom 80 were considered unsuitable for revascularization. Mortality was 26% post-PCI 16%, post-CABG and 33% among those who did not undergo revascularization (p = 0.01). On multivariable analyses, factors associated with late mortality were older age, hypertension and not undergoing CABG (all p < 0.05). Factors associated with late MI were presented with an acute coronary syndrome, whereas patients that underwent treatment with either PCI or CABG had less late MI (all p < 0.05).
Conclusion
Among consecutive diabetic patients with MVD, at a median of 6-years CABG was associated with better survival and fewer non-fatal MI outcomes compared to PCI.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:21-25
Ebrahim MEBM, Dignan R, Femia G, Kim S, ... Juergens CP, French JK
Int J Cardiol: 30 Nov 2019; 296:21-25 | PMID: 31451306
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Impact:
Abstract

Final-year medical students\' knowledge of cardiac arrest and CPR: We must do more!

Baldi E, Contri E, Bailoni A, Rendic K, ... Hertenberger N, Böttiger BW
Background
Students are an important part of the community response to an out-of-hospital cardiac arrest (OHCA). If even schoolchildren now know cardio-pulmonary resuscitation (CPR), even more the reason a young doctor should know how to treat an OHCA. The aim of our study was to assess medical students\' knowledge of CPR and OHCA throughout Europe.
Methods
An online survey was given to final-year students by the Medical Student Associations of different countries.
Results
1012 medical students from 99 different universities and 14 different countries completed the questionnaire. A total of 82.2% attended a BLS or BLS/AED course, provided by the University in only 69.7% of cases. In 84.3% it was a mandatory part of their degree. A total of 78.6% felt able to rescue a person in OHCA. Only 49.3% knew that \'unresponsiveness\' and \'absence of normal breathing\' are sufficient for lay people to identify an OHCA, and less than half of those interviewed knew the incidence of OHCA in Europe and the decrease in chance of survival if CPR is not performed. The correct compression:ventilation ratio was known by 90.2%, the correct compression depth by 69.7%, whilst only 57.8% knew the right compression rate. In total, 69.7% knew that an AED must be used immediately when available, and only 57.2% recognized the AED symbol.
Conclusions
Medical students\' knowledge of cardiac arrest and CPR needs to be improved throughout Europe and we believe that BLS/AED training should be mandatory in all European Universities.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:76-80
Baldi E, Contri E, Bailoni A, Rendic K, ... Hertenberger N, Böttiger BW
Int J Cardiol: 30 Nov 2019; 296:76-80 | PMID: 31375334
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Impact:
Abstract

The prognostic value of biventricular long axis strain using standard cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

Yang F, Wang J, Li Y, Li W, ... Han Y, Chen Y
Background
Long axis strain (LAS) is a parameter derived from standard cardiovascular magnetic resonance imaging. However, the prognostic value of biventricular LAS in hypertrophic cardiomyopathy (HCM) is unknown.
Methods
Patients with HCM (n = 384) and healthy volunteers (n = 150) were included in the study. Left ventricular (LV)-LAS was defined as the percentage change in the length measured from the epicardial border of the LV apex to the midpoint of a line connecting the mitral annulus at end-systole and end-diastole. Right ventricular (RV)-LAS represented the percentage change of length between epicardial border of the LV apex to the midpoint of a line connecting the tricuspid annulus at end-systole and end-diastole. The primary endpoint was a combination of all-cause death and sudden cardiac death aborted by appropriate implantable cardioverter-defibrillator discharge and cardiopulmonary resuscitation after syncope. The secondary endpoint was a combination of the primary endpoint and hospitalization for congestive heart failure.
Results
Twenty-nine patients (7.6%) achieved the primary endpoint, and the secondary endpoint occurred in 66 (17.2%) patients. In multivariate Cox regression analysis, RV-LAS was an independent prognostic factor for the primary (hazard ratio (HR), 1.13) and secondary (HR, 1.11) endpoints. In the subgroup of patients with a normal RV ejection fraction (EF) (>45.0%, n = 345), impaired RV-LAS was associated with adverse outcomes and might add incremental prognostic value to RVEF and tricuspid annular plane systolic excursion (TAPSE) (p < 0.01).
Conclusions
RV-LAS is an independent predictor of adverse prognosis in HCM in addition to RVEF and TAPSE.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Oct 2019; 294:43-49
Yang F, Wang J, Li Y, Li W, ... Han Y, Chen Y
Int J Cardiol: 31 Oct 2019; 294:43-49 | PMID: 31405582
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Impact:
Abstract

Story telling of myocarditis.

Zanatta A, Carturan E, Rizzo S, Basso C, Thiene G

Myocarditis was discovered as heart disease at autopsy with the use of microscope. In 1900, with the name of acute interstitial myocarditis, Carl Ludwig Alfred Fiedler first reported the history of a sudden cardiac heart failure, in the absence of coronary, valve, pericardial disease or classical specific infections with multiorgan involvement. He postulated a peculiar isolated acute inflammation of the myocardium with poor prognosis due to invisible microorganisms, which years later would have been identified as viruses. Subsequent revision of Fiedler original histologic slides by Schmorl showed cases with either lymphocytic or giant cell infiltrates. The in vivo diagnosis became possible with the right heart catheterism and endomyocardial biopsy. Employment of immunohistochemistry and molecular techniques improved the diagnosis and etiology identification. The mechanism of myocyte injury by coxsackie virus was identified in protease 2A coded by the virus and disrupting the dystrophin in the cytoskeleton. Both RNA and DNA viruses may be cardiotropic, and coxsackie and adenovirus share a common receptor (CAR). Unfortunately, vaccination is not yet available. Cardiac Magnetic Resonance is a revolutionary diagnostic tool by detecting edema, of myocardial inflammation. However endomyocardial biopsy remains the gold standard for etiological and histotype diagnosis, with limited sensitivity due to sampling error. Viral lymphocytic fulminant myocarditis may not be fatal and the employment of mechanical assistant device - ECMO in acute phase for temporary support may be lifesaving with good prognosis.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Oct 2019; 294:61-64
Zanatta A, Carturan E, Rizzo S, Basso C, Thiene G
Int J Cardiol: 31 Oct 2019; 294:61-64 | PMID: 31378380
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Impact:
Abstract

Clinical and procedural predictors and short-term survival of the patients with no reflow phenomenon after primary percutaneous coronary intervention.

Ashraf T, Khan MN, Afaque SM, Aamir KF, ... Khan AA, Karim M
Objectives
In the present study, we analysed the incidence of no-reflow phenomenon, its clinical and procedural predictors, and associated in-hospital outcomes for the patients undergoing primary percutaneous coronary intervention (PCI).
Background
No-reflow phenomenon after primary PCI is a procedural complication associated with adverse post-procedure outcomes.
Methods
Data for this study were extracted from global registry, NCDR®, the site of National Institute of Cardiovascular Disease (NICVD), Karachi from July 2017 to March 2018. The demographic, clinical, and procedural characteristics, and in-hospital outcomes were analysed for the patients with and without no-reflow after primary PCI.
Results
Of total of 3255 patients, no-reflow phenomenon was found in 132 (4.1%) patients and it was associated with significantly higher in-hospitality mortality (6.8% vs. 2.9%; p = 0.01), cerebrovascular accident (1.5% vs. 0%; p < 0.001), post procedure bleeding (2.3% vs. 0.5%; p = 0.009), and cardiogenic shock (3.8% vs. 1.2%; p = 0.011). The multivariate analysis showed advanced age [odds ratio = 1.63, 95% confidence interval 1.09-2.44, p = 0.018], diabetes [1.66, 1.14-2.42, p = 0.009], prior history of CABG [8.70, 1.45-52.04, p = 0.018], low pre-procedure TIMI flow grade [2.04, 1.3-3.21, p = 0.002], longer length of target lesion [1.51, 1.06-2.16, p = 0.023], and 10 fold raised troponin I [1.55, 1.08-2.23, p = 0.018] were the independent predictors of no-reflow.
Conclusions
In this selected group of patients, the no-reflow phenomenon after primary percutaneous coronary intervention is not that uncommon. It is associated with an increased risk of adverse post-procedure hospital course including mortality. Pathophysiology of the no-reflow phenomenon is complex and opaque, however, it can be predicted based on certain clinical and procedural characteristics.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Oct 2019; 294:27-31
Ashraf T, Khan MN, Afaque SM, Aamir KF, ... Khan AA, Karim M
Int J Cardiol: 31 Oct 2019; 294:27-31 | PMID: 31387823
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Impact:
Abstract

Atrial fibrillation in highly trained endurance athletes - Description of a syndrome.

Sanchis-Gomar F, Perez-Quilis C, Lippi G, Cervellin G, ... Serrano-Ostáriz E, Lucia A
Atrial fibrillation (AF) is the most common heart arrhythmia, the risk of which typically increases with age. This condition is commonly associated with major cardiovascular diseases and structural heart damage, while it is rarely observed in healthy young people. However, increasing evidence indicates that paroxysmal AF can also onset in young or middle-aged and otherwise healthy endurance athletes (e.g., cyclists, runners and cross-country skiers). Here we review the topic of AF associated with strenuous endurance exercise (SEE), for example cycling, running and cross-country skiing, especially at a competitive level, and we propose the definition of a new syndrome based on the accumulating data in the literature: SEE-related AF under the acronym of \'PAFIYAMA\' (\'paroxysmal AF in young and middle-aged athletes\'). Special emphasis is given to the proper differentiation of PAFIYAMA from \'classical AF\' regarding pathophysiology, diagnosis and medical management.

Int J Cardiol: 23 Oct 2016; 226:11-20
Sanchis-Gomar F, Perez-Quilis C, Lippi G, Cervellin G, ... Serrano-Ostáriz E, Lucia A
Int J Cardiol: 23 Oct 2016; 226:11-20 | PMID: 27776250
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Impact:
Abstract

Gastrointestinal complications associated with catheter ablation for atrial fibrillation.

Garg L, Garg J, Gupta N, Shah N, ... Bozorgnia B, Natale A
Atrial fibrillation is the most common arrhythmia in the United States. With the ageing population, the incidence and prevalence of atrial fibrillation are on the rise. Catheter ablation of atrial fibrillation is a widely accepted treatment modality in patients with drug refractory symptomatic paroxysmal or persistent atrial fibrillation. The close proximity to the left atrium posterior wall makes the thermosensitive esophagus a potential site of injury during catheter ablation of AF leading to various gastrointestinal complications. The major gastrointestinal complications associated with catheter ablation include atrioesophageal fistula, gastroparesis, esophageal thermal lesions and esophageal ulcers. Multiple studies, case reports and series have described these complications with various catheter ablation techniques such as radiofrequency, cryoenergy and high frequency focused ultrasound energy ablation. This review addresses the gastrointestinal complications after AF ablation procedures and aims to provide the clinicians with an overview of clinical presentation, etiology, pathogenesis, prevention and management of these conditions.

Int J Cardiol: 29 Sep 2016; 224:424-430
Garg L, Garg J, Gupta N, Shah N, ... Bozorgnia B, Natale A
Int J Cardiol: 29 Sep 2016; 224:424-430 | PMID: 27690340
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Impact:
Abstract

Climate changes and ST-elevation myocardial infarction treated with primary percutaneous coronary angioplasty.

Versaci F, Biondi-Zoccai G, Giudici AD, Mariano E, ... Federici M, Romeo F
Background
The impact of seasonal changes on the incidence of acute myocardial infarction has been incompletely appraised, especially in the modern era of primary percutaneous coronary intervention (PPCI). We aimed to appraise the overall and season-specific impact of climate changes on the daily rate of PCCI.
Methods
Details on PPCI and climate changes were retrospectively collected in three high-volume Italian institutions with different geographical features. The association between rate of PPCI and temperature, atmospheric pressure (ATM), humidity and rainfall was appraised with Poisson models, with overall analyses and according to season of the year.
Results
Details on 6880 days with a total of 4132 PPCI were collected. Overall adjusted analysis showed that higher minimum atmospheric pressure 3 days before PPCI were associated with lower risk (regression coefficient = 0.999 [95% confidence interval 0.998-1.000], p = 0.030). Focusing on season, in Winter PPCI rates were increased by lower same day mean temperature (0.973 [0.956-0.990], p = 0.002) and lower rainfall (0.980 [0.960-1.000], p = 0.049). Conversely, in Spring greater changes in atmospheric pressure 3 days before PPCI were associated with increased risk (1.023 [1.002-1.045], p = 0.032), with similar effects in Summer for minimum temperature on the same day (1.022 [1.001-1.044], p = 0.040).
Conclusions
Climate has a significant impact on the risk of PPCI in the current era, with a complex interplay according to season. Higher risk risk is expected with lower minimum atmospheric pressure in the preceding days, lower rainfall in Winter, greater changes in atmospheric pressure in Spring, and higher temperatures in Summer. These findings have important implications for prevention strategies.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Oct 2019; 294:1-5
Versaci F, Biondi-Zoccai G, Giudici AD, Mariano E, ... Federici M, Romeo F
Int J Cardiol: 31 Oct 2019; 294:1-5 | PMID: 31301864
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Impact:
Abstract

Is it time to change how we think about incomplete coronary revascularization?

Spadaccio C, Nappi F, Nenna A, Beattie G, Chello M, Sutherland FW
The optimal degree of revascularization for patients with chronic multivessel coronary artery disease remains an unsolved issue. Intuitively, complete revascularization decreases cardiovascular events and improves outcomes compared to incomplete procedures, but in recent years the concept of incomplete revascularization moved from a sub-optimal or a defective treatment towards the most appropriate revascularization technique in some categories of patients. A reasonable level of incomplete anatomic revascularization has been shown to be safe and achievable with both percutaneous (PCI) and surgical procedures (CABG), despite with different long-term outcomes. What are the mechanisms underlying the clinical benefits of an incomplete revascularization and what are the factors explaining the discrepancy in the long-term clinical outcomes between the two modes of revascularization PCI and CABG? The biological consequences of coronary reperfusion might provide valuable hints in this context and at the same time cast new light on the way we think about incomplete revascularization.

Int J Cardiol: 24 Sep 2016; 224:295-298
Spadaccio C, Nappi F, Nenna A, Beattie G, Chello M, Sutherland FW
Int J Cardiol: 24 Sep 2016; 224:295-298 | PMID: 27665400
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Impact:
Abstract

Myocardial involvement in Chagas disease: Insights from cardiac magnetic resonance.

Regueiro A, García-Álvarez A, Sitges M, Ortiz-Pérez JT, ... Gascón J, Sanz G
Background: Chagas\' disease is becoming a public health problem in Europe because of migratory movements. Cardiac magnetic resonance (CMR) has emerged as a non-invasive tool to assess cardiac tissue characteristics. There is scarce data available on CMR in patients with Chagas\' disease. Objective: To describe CMR findings in patients with Chagas\' disease living in a non-endemic area focusing on differentiation from other cardiomyopathies and relation with clinical status. Methods and results: Sixty-seven Chagas\' disease patients divided into 3 groups-group 1 (indeterminate form: positive serology without ECG or 2D-echocardiographic abnormalities; N=27), group 2 (ECG abnormalities of Chagas\' disease but normal 2D-echocardiography; N=19), and group 3 (regional wall motion abnormalities, LV end-diastolic diameter >55mm or LV ejection fraction <50% on echocardiography; N=21)-were studied. The presence of wall motion abnormalities and delayed enhancement (DE) by CMR was more frequent in the inferolateral and apical segments. DE distribution in the myocardial wall was heterogeneous (subendocardial 26.8%, midwall 14.0%, subepicardial 22.6%, and transmural 36.0% of total segments with DE) and related to larger cardiac chambers and worse systolic function. Conclusion: Pattern of DE in Chagas\' disease may mimic that of both ischemic and nonischemic cardiomyopathies, with especial predilection for the apical and inferolateral segments of the left ventricle. These findings support that myocardial involvement in chronic Chagas\' cardiomyopathy (CCC) may be due to both microvascular disturbances and chronic myocarditis and may favor CCC in the differential diagnosis of patients with compatible epidemiological history and heart failure of uncertain etiology.

Int J Cardiol: 12 Sep 2011; epub ahead of print
Regueiro A, García-Álvarez A, Sitges M, Ortiz-Pérez JT, ... Gascón J, Sanz G
Int J Cardiol: 12 Sep 2011; epub ahead of print | PMID: 21907431
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Impact:
Abstract

The changing face of cardiovascular disease 2000-2012: An analysis of the world health organisation global health estimates data.

McAloon CJ, Boylan LM, Hamborg T, Stallard N, ... Lim PB, Hayat SA
The pattern and global burden of disease has evolved considerably over the last two decades, from primarily communicable, maternal, and perinatal causes to non-communicable disease (NCD). Cardiovascular disease (CVD) has become the single most important and largest cause of NCD deaths worldwide at over 50%. The World Health Organisation (WHO) estimates that 17.6 million people died of CVD worldwide in 2012. Proportionally, this accounts for an estimated 31.43% of global mortality, with ischaemic heart disease (IHD) accounting for approximately 7.4 million deaths, 13.2% of the total. IHD was also the greatest single cause of death in 2000, accounting for an estimated 6.0 million deaths. The global burden of CVD falls, principally, on the low and middle-income (LMI) countries, accounting for over 80% of CVD deaths. Individual populations face differing challenges and each population has unique health burdens, however, CVD remains one of the greatest health challenges both nationally and worldwide.

Int J Cardiol: 23 Sep 2016; 224:256-264
McAloon CJ, Boylan LM, Hamborg T, Stallard N, ... Lim PB, Hayat SA
Int J Cardiol: 23 Sep 2016; 224:256-264 | PMID: 27664572
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Impact:
Abstract

Pharmacokinetics and pharmacodynamics of cardiovascular drugs in chronic heart failure.

Lainscak M, Vitale C, Seferovic P, Spoletini I, Cvan Trobec K, Rosano GM
Pharmacotherapy in chronic heart failure (HF) is challenging, due to the diverse neuroendocrine, inflammatory, metabolic and immunological mechanisms involved in its pathogenesis, the presence of co-morbidities and use of multiple therapies. Further, physiological parameters influencing drug pharmacokinetics (PKs) and pharmacodynamics (PDs) may be altered in patients with HF. There is growing evidence that the disease-induced physiological changes may influence the PKs and PDs of all drugs used in patients with HF. Therapeutic approaches should consider all factors that might influence the response to treatment and dosage should be tailored to individual patients. Hence, further studies are required to understand the PK and PD differences between chronic HF patients and healthy subjects. Because PK is difficult to be assessed in the individual patient with HF, PD effects should be used to tailor therapy in patients with HF.

Int J Cardiol: 21 Sep 2016; 224:191-198
Lainscak M, Vitale C, Seferovic P, Spoletini I, Cvan Trobec K, Rosano GM
Int J Cardiol: 21 Sep 2016; 224:191-198 | PMID: 27657473
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Impact:
Abstract

Mortality in adult congenital heart disease: Are national registries reliable for cause of death?

Zomer AC, Uiterwaal CS, der Velde ET, Tijssen JG, ... Grobbee DE, Mulder BJ
Background: Statistics on cause-specific mortality are important for prognostic research. The aim of this study was to assess the utility of the national mortality registry in research on causes of death in adult patients with congenital heart disease (CHD). Methods: The CONCOR registry of over 10,000 adults with CHD was used to verify the causes of death provided by the WHO guidelines based national mortality registry, by linkage. Results: Of 7277 patients linked to the national mortality registry, 196 (2.4%) were recorded deceased, versus 228 deceased patients (3.1%) recorded in the CONCOR registry, during a follow-up of 25,900 patient years. Median age at death was 48.9years. Of all deaths in the CONCOR registry, 77% had a cardiovascular origin; nearly 50% were due to progressive heart failure and arrhythmias. The national mortality registry recorded death due to progressive heart failure and arrhythmias in only 8.5%. Moreover, this registry recorded death with an \'unspecified\' cause in approximately 30%, primarily containing patients who died due to progressive heart failure and arrhythmias according to their medical records. Conclusion: WHO guidelines based national mortality registries lack the specificity and completeness needed for accurate research on causes of death in adult patients with CHD.

Int J Cardiol: 02 Aug 2010; epub ahead of print
Zomer AC, Uiterwaal CS, der Velde ET, Tijssen JG, ... Grobbee DE, Mulder BJ
Int J Cardiol: 02 Aug 2010; epub ahead of print | PMID: 20674998
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Abstract

Depression in heart failure: Intricate relationship, pathophysiology and most updated evidence of interventions from recent clinical studies.

Ghosh RK, Ball S, Prasad V, Gupta A
Heart failure (HF) is a burgeoning chronic health condition affecting more than 20million people worldwide. Patients with HF have a significant (17.1%) 30-day readmission rate, which invites substantial penalty in payment to hospitals from Centers for Medicare and Medicaid Services, as per the newly introduced Hospital Readmissions Reduction Program. Depression is one of the important risk factors for readmission in HF patients. It has a significant prevalence in patients with HF and contributes to the overall poor quality of life in them. Several behavioral (smoking, obesity, lack of exercise and medication noncompliance) and pathophysiological factors (hypercortisolism, elevated inflammatory biomarkers, fibrinogen, and atherosclerosis) have been found responsible for the adverse outcome in patients with HF and concomitant depression. Hippocampal volume loss noted in patients with acute HF exacerbations may contribute to the development of depressive symptoms in them. Screening for depression in HF patients continues to be challenging due to a considerable overlap in symptoms. Published trials on the use of antidepressants and cognitive behavioral therapy (CBT) have shown variable outcomes. Newer modalities like internet-based CBT have been tried in small studies, with promising results. A recent meta-analysis observed the beneficial role of aerobic exercise training in patients with HFrEF. Future long-term prospective studies may contribute to the formulation of a detailed screening and management guideline for patients with HF and depression. Our review is aimed to summarize the intricate relationship between depression and heart failure, with respect to their epidemiology, pathophysiological aspects, and optimal management approach.

Int J Cardiol: 21 Sep 2016; 224:170-177
Ghosh RK, Ball S, Prasad V, Gupta A
Int J Cardiol: 21 Sep 2016; 224:170-177 | PMID: 27657469
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Impact:
Abstract

Effect of ivabradine on central aortic blood pressure in patients with stable coronary artery disease: What do we know?

Lopatin YM, Vitale C
Treatment of hypertensive patients with beta-blockers decreases central blood pressure (CBP) less than other antihypertensive drugs, which is believed to account for their lesser cardiovascular protection in this setting. Some authors have suggested that decreasing heart rate (HR) with beta-blockers would increase CBP. In contrast to beta-blockers, the anti-anginal agent ivabradine reduces HR without other hemodynamic effects, and represents an attractive tool for exploring the direct relationship between HR and CBP. Here, we review the available clinical data assessing the effect of selective HR reduction with ivabradine on CBP in patients with stable coronary artery disease (CAD). We collected data from five studies which report either increase, decrease, or neutral effects of ivabradine on CBP. Further studies are needed to clarify the exact role of ivabradine on CBP. However, as supported by its pharmacodynamic effect in patients with stable CAD, available evidence to date suggests that ivabradine does not negatively impact CBP when associated with beta-blocker. HR reduction with both beta-blockers and ivabradine remains well-established treatments for the symptomatic treatment of angina patients.

Int J Cardiol: 21 Sep 2016; 224:145-148
Lopatin YM, Vitale C
Int J Cardiol: 21 Sep 2016; 224:145-148 | PMID: 27657463
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Impact:
Abstract

The C of CHADS: Historical perspective and clinical applications for anticoagulation in patients with non valvular atrial fibrillation and congestive heart failure.

Chugh Y, Faillace RT
The risk stratification of patients with coexisting non valvular atrial fibrillation and congestive heart failure, is often a clinical challenge, as the definitions of congestive heart failure in the popular CHADS2 and CHA2DS2VASc scoring systems, and amongst major clinical trials on Warfarin and Novel Oral Anticoagulants (NOAC) have heterogeneity. Available evidence reveals that any heart failure and/or left ventricular systolic dysfunction is associated with higher rates of stroke/systemic embolism and bleeding in patients with non valvular atrial fibrillation compared to patients without heart failure and normal left ventricular function. Most standard dose NOAC regimens have a better safety and efficacy profile over warfarin in most heart failure sub-group types with a few exceptions including patients with NYHA III/IV on Dabigatran 150mg BID from the RE-LY trial, who had higher major bleeding events, and patients with asymptomatic left ventricular dysfunction (ejection fraction ≤40%) and heart failure with reduced ejection fraction on 20mg of Rivaroxaban in the ROCKET-AF trial, when compared to patients on Warfarin in the corresponding groups. With the gaining popularity and use of NOACs, understanding their safety profile in such situations is paramount.

Int J Cardiol: 02 Oct 2016; 224:431-436
Chugh Y, Faillace RT
Int J Cardiol: 02 Oct 2016; 224:431-436 | PMID: 27693993
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Impact:
Abstract

Predictive model for late atrial arrhythmia after closure of an atrial septal defect.

De Bruaene AV, Moons P, Belmans A, Post MC, ... Morissens M, Budts W
ObjectiveS: To develop a quantitative event-free prediction model of late atrial arrhythmia after atrial septal defect (ASD) repair. Background: The clinical management of ASD is driven by risk factors that determine the occurrence of late atrial arrhythmia. Methods: Data from ASD type secundum patients, included in the Belgian Congenital Heart Disease Registry, were analyzed. Based on review of the literature, age at repair, gender, pulmonary hypertension, atrial arrhythmia before and within one month after repair were included in the model. Using Cox-regression analysis, a weighted risk score was derived, which was validated using the Brier score. Results: A total of 155 patients (117 women; median age at follow-up 53.9years, range 18.0-78.8) having 349 follow-up years was included. Thirty-nine patients (25.2%) presented with late atrial arrhythmia. Multivariate analysis showed that a mPAP≥25mmHg (HR 4.39; 95%CI 2.17-9.09; P<0.0001), the presence of atrial arrhythmia before (HR 3.52; 95%CI 1.75-7.14; P=0.002) and≤1month after repair (HR 6.62; 95%CI 2.38-20.00; P<0.0001) and gender (HR 2.18 95%CI 1.11-4.35) were associated with late atrial arrhythmia. A risk score (0 to 28 points) to predict atrial arrhythmia free survival was derived for follow-up times ranging from one to 5years. Mean Brier score for the model was 0.10. Conclusions: We formulated a well validated risk model to predict arrhythmia-free survival in ASD patients undergoing ASD repair. Further research is needed whether this model can be used for individual clinical risk stratification and whether the model can be adapted for application in other congenital heart defects.

Int J Cardiol: 01 Aug 2011; epub ahead of print
De Bruaene AV, Moons P, Belmans A, Post MC, ... Morissens M, Budts W
Int J Cardiol: 01 Aug 2011; epub ahead of print | PMID: 21802750
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Impact:
Abstract

Cardiac remodeling with rhythm versus rate control strategies for atrial fibrillation in patients with heart failure: Insights from the AF-CHF echocardiographic sub-study.

Henrard V, Ducharme A, Khairy P, Gisbert A, ... Tardif JC, for the AF-CHF investigators
Background: In patients with heart failure and atrial fibrillation, the AF-CHF (Atrial Fibrillation and Congestive Heart Failure) trial did not demonstrate the superiority of rhythm control (RhyC) over a rate control (RaC) strategy on cardiovascular mortality. Nevertheless, deleterious hemodynamic effects of atrial fibrillation can lead to further decrease in left ventricular (LV) function and progression of symptoms. This echocardiographic sub-study was designed to compare the effects of the two treatment strategies on LV ejection fraction (LVEF), chamber volumes and dimensions, valvular regurgitation and functional status. Methods and results: A total of 59 patients (29 RhyC, 30 RaC) aged 67±8years (14% women), enrolled in the AF-CHF trial at the Montreal Heart Institute underwent standardized echocardiograms at baseline and at 12months. Mean LVEF at baseline was severely depressed (RhyC: 27.0±4.9% and RaC: 27.6±7.4%, p=0.73), and improved to a similar degree in both groups (RhyC: +8.0±10.4% and RaC: +4.5±10.6, both p<0.05; p=0.19 for RhyC versus RaC). Other echocardiographic parameters, such as LV end-systolic volume index and degree of mitral and tricuspid regurgitation, remained unchanged. New York Heart Association functional class and distance walked in 6min improved significantly in both groups (RhyC: +48.9±78.7m and RaC: +47.2±96.7m, both p≤0.01), with no difference between RhyC and RaC strategies. Conclusions: Improvements in LVEF and functional status are observed after 12months in patients with heart failure and atrial fibrillation, regardless of whether rate or rhythm control strategies are used.

Int J Cardiol: 15 Sep 2011; epub ahead of print
Henrard V, Ducharme A, Khairy P, Gisbert A, ... Tardif JC, for the AF-CHF investigators
Int J Cardiol: 15 Sep 2011; epub ahead of print | PMID: 21917326
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Impact:
Abstract

Long term outcome of mechanical valve prosthesis in the pulmonary position.

Dos L, Muñoz-Guijosa C, Mendez AB, Ginel A, ... Padro JM, Subirana MT
ObjectiveS: Assessment of the long term outcome of mechanical valve prosthesis at pulmonary position in a population of grown-up congenital heart disease patients from a tertiary referral center. Methods: From 1977 to 2007, 22 consecutive patients underwent a total of 25 pulmonary valve replacements with mechanical prosthesis. The most frequent underlying cardiac condition was tetralogy of Fallot (n=16, 64%) and the mean age at the time of pulmonary valve replacement was 32+/-11years (range 14-50years). Results: The postoperative mortality rate was 4% (n=1) with no late deaths documented after a mean follow-up of 7.6+/-7.6years (range 0.29-24years). No major bleeding episodes occurred. Three patients presented with valve thrombosis in the setting of long term anticoagulation withdrawal and required valve re-replacement. Two of these patients, both with poor right ventricular function and overt clinical signs of right heart failure at the time of valve re-replacement, experienced further episodes of thrombosis despite correct anticoagulation. All episodes resolved with thrombolysis. After addition of antiplatelet treatment in one case and anticoagulation self-control, in the other, no further thrombosis has been documented. Conclusions: Mechanical valve prosthesis may be an alternative to tissue valve prosthesis in patients with congenital heart disease requiring pulmonary valve replacement. Optimal anticoagulation is crucial and additional antiplatelet treatment should be considered. Our data also suggest that patients with severe right ventricular dysfunction and congestive heart failure might be at particular risk for valve thrombosis.

Int J Cardiol: 04 May 2010; epub ahead of print
Dos L, Muñoz-Guijosa C, Mendez AB, Ginel A, ... Padro JM, Subirana MT
Int J Cardiol: 04 May 2010; epub ahead of print | PMID: 20439120
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Abstract

Red blood cell distribution width predicts new-onset anemia in heart failure patients.

Pascual-Figal DA, Bonaque JC, Manzano-Fernández S, Fernández A, ... Valdes M, Januzzi JL
Background: Hematologic abnormalities such as elevated red blood cell distribution width (RDW) as well as anemia are prognostically meaningful among heart failure (HF) patients. The inter-relationship between these hematologic abnormalities in HF is unclear, however. We therefore aimed to assess whether RDW is predicting changes in hemoglobin concentrations as well as onset of anemia. Methods: 268 consecutive non-anemic patients with acutely decompensated HF (ADHF) were enrolled at hospital discharge and RDW was measured. At 6month follow-up, change in hemoglobin as well as new-onset anemia was studied as a function of RDW at discharge. Results: RDW at discharge correlated negatively with hemoglobin values at 6months (r=-0.220; p<0.001); a greater decrease in hemoglobin concentration occurred in those with higher values of RDW at discharge (p=0.004), independently of baseline hemoglobin concentration and other risk factors. At 6months, 54 patients (20%) developed new-onset anemia. RDW values at discharge were significantly higher among patients who developed new-onset anemia (15.1±2.2 vs. 14.2±1.4, p=0.005). In integrated discrimination improvement analyses, the addition of RDW measurement improved the ability to predict new-onset anemia (IDI 0.0531, p<0.001), beyond known risk factors as hemoglobin, renal function, age, diabetes mellitus, sex and HF symptom severity. In adjusted analyses, patients with RDW>15% (derived from receiver operating characteristic analysis) had a tripling of the risk of new-onset anemia (OR=3.1, 95% CI 1.5-5.1, p=0.002). Conclusion: Among non-anemic patients with ADHF, RDW measurement at the time of hospital discharge independently predicts lower hemoglobin concentrations and new-onset anemia over a 6-month follow up period.

Int J Cardiol: 10 May 2011; epub ahead of print
Pascual-Figal DA, Bonaque JC, Manzano-Fernández S, Fernández A, ... Valdes M, Januzzi JL
Int J Cardiol: 10 May 2011; epub ahead of print | PMID: 21555160
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Abstract

Rationale and benefits of trimetazidine by acting on cardiac metabolism in heart failure.

Lopatin YM, Rosano GM, Fragasso G, Lopaschuk GD, ... Jourdain P, Ponikowski P
Heart failure is a systemic and multiorgan syndrome with metabolic failure as a fundamental mechanism. As a consequence of its impaired metabolism, other processes are activated in the failing heart, further exacerbating the progression of heart failure. Recent evidence suggests that modulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation represents a promising approach to the treatment of patients with heart failure. Clinical trials have demonstrated that the adjunct of trimetazidine to the conventional medical therapy improves symptoms, cardiac function and prognosis in patients with heart failure without exerting negative hemodynamic effects. This review focuses on the rationale and clinical benefits of trimetazidine by acting on cardiac metabolism in heart failure, and aims to draw attention to the readiness of this agent to be included in all the major guidelines dealing with heart failure.

Int J Cardiol: 29 Nov 2015; 203:909-915
Lopatin YM, Rosano GM, Fragasso G, Lopaschuk GD, ... Jourdain P, Ponikowski P
Int J Cardiol: 29 Nov 2015; 203:909-915 | PMID: 26618252
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Abstract

Cardiovascular manifestations of mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome).

Golda A, Jurecka A, Tylki-Szymanska A
The aim of the article is to gather and summarize the published data about the incidence, course of illness, treatment possibilities and complications of cardiovascular disorders in patients with mucopolysaccharidosis type VI (MPS VI) also known as Maroteaux-Lamy syndrome. MPS VI is a lysosomal storage disorder caused by deficient activity of N-acetylogalactosamine-4-sulfatase leading to progressive intracellular accumulation of glycosaminoglycans. The relatively low birth prevalence ranging from 1 in 43,000 to1 in 1.5 million births mirrors the limited descriptions of the cardiovascular disorders in the medical literature. Patients with MPS VI can be specifically treated with enzyme replacement therapy. Extra-cardiac features include growth retardation, coarse facial features, stiff joints, skeletal malformations (dysostosis multiplex), respiratory problems, corneal clouding, and hepatosplenomegaly. The clinical presentation varies considerably, however the development of heart disease and cardiac dysfunction is a serious problem in the majority of patients. The most characteristic cardiac presentation is valvular disease, while other MPS VI patients also develop cardiomyopathy, fibroelastosis, pulmonary hypertension, cardiac conduction system disorders and other complications. There are also reports on acute heart failure. Early cardiovascular manifestation may escape detection since joint stiffness or skeletal malformations limit maximal exercise levels and respiratory system involvement may mask the underlining cardiac insufficiency. A correct and timely diagnosis offers the possibility of disease-specific treatment leading to sustained clinical benefits for cardiac and non-cardiac MPS VI manifestations.

Int J Cardiol: 08 Jul 2011; epub ahead of print
Golda A, Jurecka A, Tylki-Szymanska A
Int J Cardiol: 08 Jul 2011; epub ahead of print | PMID: 21737154
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Abstract

Telomere/telomerase system impairment in circulating angiogenic cells of geriatric patients with heart failure.

Olivieri F, Antonicelli R, Recchioni R, Mariotti S, ... Latini R, Procopio AD
Background: The functional characteristics of circulating angiogenic cells (CACs) are impaired in congestive heart failure (CHF) patients, suggesting that CAC dysfunction could contribute to CHF pathogenesis. However, the underlying mechanisms are only partly unraveled. No data are currently available regarding telomere/telomerase system in CACs of CHF patients. Methods: CACs were obtained from 80 subjects: 40 healthy control subjects (CTR) [median age (IQR), 80 (76-85yrs)] and 40 patients affected by post-ischemic cardiomyopathy CHF [median age (IQR), 82 (77-89)]. CAC and leukocyte telomere length, assessed as T/S ratio, and telomerase (TERT) activity were determined in all the enrolled subjects. Specificity and sensitivity of CAC and leukocyte T/S in discriminating between CHF and CTR were evaluated using Receiver Operator Characteristic (ROC) curve analysis and reported as AUC values. CD34+/VEGFR2+ number and pro-inflammatory cytokines plasma levels, such as IL-6 and TNF-α, were also measured. Results: CAC T/S and TERT activity were significantly reduced in CHF patients compared to CTR subjects. In leukocytes, only a significant T/S reduction was observed. AUC values were higher for CAC T/S with respect to leukocyte T/S (AUC=0.89, and AUC=0.73, P<0.01, respectively). In multivariate analysis, leukocyte T/S, CAC T/S, CAC TERT activity and NT-proBNP levels were confirmed as parameters significantly associated with CHF. CD34+/VEGFR2+ number, IL-6 and TNF-α plasma levels were significantly increased in CHF patients. Conclusions: CACs from CHF patients are characterized by telomere/telomerase system impairment, providing new insight into the clinical relevance of CACs in CHF pathogenesis.

Int J Cardiol: 08 Jul 2011; epub ahead of print
Olivieri F, Antonicelli R, Recchioni R, Mariotti S, ... Latini R, Procopio AD
Int J Cardiol: 08 Jul 2011; epub ahead of print | PMID: 21737157
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Abstract

Impact of heart failure on in-hospital outcomes of acute coronary syndrome patients in China - Results from the Bridging the Gap on CHD Secondary Prevention in China (BRIG) project.

Wang N, Zhao D, Liu J, Liu J, ... Du F, on behalf of the BRIG project
Background: Treatments of acute coronary syndrome (ACS) and heart failure (HF) have progressed greatly in the past decades. However, few data are currently available regarding the impact of HF on the in-hospital outcomes of ACS patients, under current treatment status, in China. Methods: A total of 65 hospitals from all 31 provinces of mainland China and the Hong Kong special administrative region were recruited using a multistage non-randomized sampling approach. A questionnaire was completed according to the medical records of 3168 ACS patients, of which 706 (22.3%) had acute HF and 262 (8.3%) HF patients did not have an episode of acute HF during hospitalization. Results: The rates of in-hospital mortality and composite end-point events (death, myocardial re-/infarction, serious arrhythmia and stroke) of acute HF patients were significantly higher than those of HF patients without an acute episode and patients without HF. After adjustment for other factors (including age, ACS types and in-hospital treatments, etc.), acute HF remained to be a potent independent predictor of in-hospital mortality and composite end-point events for ACS patients (OR=7.50, 95% CI=4.32-13.02 and OR=2.74, 95% CI=2.15-3.48, respectively). The utilization rates of guideline recommended treatments for ACS complicating HF, such as β-blockers (67.6%) and PCI (17.4%), were low in the acute HF patients. Conclusions: Under current treatment status, acute HF during hospitalization still rendered higher rates of in-hospital mortality and composite end-point events in the studied ACS patients in China.

Int J Cardiol: 01 Apr 2011; epub ahead of print
Wang N, Zhao D, Liu J, Liu J, ... Du F, on behalf of the BRIG project
Int J Cardiol: 01 Apr 2011; epub ahead of print | PMID: 21453979
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Abstract

Regulatory T lymphocytes in myocardial infarction: A promising new therapeutic target.

Wang YP, Xie Y, Ma H, Su SA, ... Wang JA, Xiang MX
Myocardial infarction (MI) is one of the leading causes of death especially in developed countries. Although the advent of early myocardial reperfusion therapy contributes to decreasing the mortality of patients with MI, cardiac ischemia-reperfusion injury and adverse remodeling during the repair process still remain the major factors impairing cardiac function and resulting in unsatisfactory prognosis. Excessive inflammation and immune responses play a crucial role during the whole process of MI. Regulatory T lymphocytes, characterized by immunosuppressive capacity, are associated with many immune-related diseases. Recent studies have proven a protective role of regulatory T cells in MI, which is mainly achieved by modulating inflammation and immune responses. In this review, we will summarize current knowledge of regulatory T lymphocytes, and highlight their roles in the onset of MI, ischemia-reperfusion injury, as well as post-infarct cardiac healing and remodeling.

Int J Cardiol: 29 Nov 2015; 203:923-928
Wang YP, Xie Y, Ma H, Su SA, ... Wang JA, Xiang MX
Int J Cardiol: 29 Nov 2015; 203:923-928 | PMID: 26618254
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Abstract

Genetic basis of dilated cardiomyopathy.

Pérez-Serra A, Toro R, Sarquella-Brugada G, de Gonzalo-Calvo D, ... Brugada R, Campuzano O
Dilated cardiomyopathy is a rare cardiac disease characterized by left ventricular dilatation and systolic dysfunction leading to heart failure and sudden cardiac death. Currently, despite several conditions have been reported as aetiologies of the disease, a large number of cases remain classified as idiopathic. Recent studies determine that nearly 60% of cases are inherited, therefore due to a genetic cause. Progressive technological advances in genetic analysis have identified over 60 genes associated with this entity, being TTN the main gene, so far. All these genes encode a wide variety of myocyte proteins, mainly sarcomeric and desmosomal, but physiopathologic pathways are not yet completely unraveled. We review the recent published data about genetics of familial dilated cardiomyopathy.

Int J Cardiol: 12 Oct 2016; 224:461-472
Pérez-Serra A, Toro R, Sarquella-Brugada G, de Gonzalo-Calvo D, ... Brugada R, Campuzano O
Int J Cardiol: 12 Oct 2016; 224:461-472 | PMID: 27736720
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Abstract

Neuromuscular electrical stimulation for muscle wasting in heart failure patients.

Saitoh M, Dos Santos MR, Anker M, Anker SD, von Haehling S, Springer J
Neuromuscular electrical stimulation (NMES) seems to be safe and beneficial in improvement in functional capacity, muscle strength, and quality of life when compared with conventional aerobic exercise, while the change in muscle fiber composition and muscle size was conflicting in patients with heart failure (HF). Moreover, NMES studies seem to have beneficial effects on pro-inflammatory cytokine, oxidative enzyme activity, and protein anabolic and catabolic metabolism that are the key molecular mechanism of muscle wasting in patients with HF. We review specific issues related to the effects of NMES on muscle wasting in patients with HF, whether NMES seems to be an alternative exercise modality preventing or improving in muscle wasting for HF patients who are unable or unwilling to engage in conventional exercise training; however no established strategies currently exist to focus on the patients with HF accompanied by muscle wasting.

Int J Cardiol: 10 Oct 2016; 225:200-205
Saitoh M, Dos Santos MR, Anker M, Anker SD, von Haehling S, Springer J
Int J Cardiol: 10 Oct 2016; 225:200-205 | PMID: 27728864
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Abstract

Patients with calcific aortic stenosis exhibit systemic molecular evidence of ischemia, enhanced coagulation, oxidative stress and impaired cholesterol transport.

Mourino-Alvarez L, Baldan-Martin M, Gonzalez-Calero L, Martinez-Laborde C, ... de la Cuesta F, Barderas MG
The most common valve diseases are calcific aortic stenosis (AS) and aortic regurgitation (AR). The former is characterized by thickening of valve leaflets followed by progressive calcification, which produces progressive aortic valve (AV) narrowing, increased pressure afterload on the left ventricle (LV) and subsequent LV hypertrophy. On the other hand, AR is due to malcoaptation of the valve leaflets with resultant diastolic reflux of blood from aorta back to the LV producing volume and pressure overload and progressive LV dilatation. In order to isolate the molecular mechanisms taking place during AS, we have used an integrated "-omic" approach to compare plasma samples from AS and from AR patients used as controls. The final purpose of this work is to find molecular changes in response to the calcification of the AV, diminishing the effects of the AV dysfunction.

Int J Cardiol: 06 Oct 2016; 225:99-106
Mourino-Alvarez L, Baldan-Martin M, Gonzalez-Calero L, Martinez-Laborde C, ... de la Cuesta F, Barderas MG
Int J Cardiol: 06 Oct 2016; 225:99-106 | PMID: 27716559
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Abstract

Does modifying electrode placement of the 12 lead ECG matter in healthy subjects?

Sheppard J, Barker T, Ranasinghe A, Clutton-Brock T, Frenneaux M, Parkes M
Background: Limb electrodes for the 12 lead ECG are routinely placed on the torso during exercise stress testing or when limbs are clinically inaccessible. It is unclear whether such electrode modification produces ECG changes in healthy male or female subjects that are clinically important according to the 2009 AHA, ACCF, HRS guidelines. We therefore measured whether ECG modification produced clinically important or false positive ECG changes e.g., appearance of Q waves in leads V(1-3), ST changes greater than 0.1mV, T wave changes greater than 0.5mV (frontal plane) or 1mV (transverse plane), QRS axis shifts or alterations to QTc/P-R/QRS intervals. Methods: The 12 lead ECG was measured in 18 healthy and semi-recumbent subjects using the standard and Takuma modified limb placements. Results: In the frontal plane we demonstrate that the modification of limb electrode placement produces small Q, R and T wave amplitude and QRS axis changes that are statistically but not clinically significant. In the transverse plane it produces no statistically or clinically significant changes in the ECG or in ST segment morphology, P-R, QRS or QTc intervals. Conclusions: We provide better and more robust evidence that routine modification of limb electrode placement produces only minor changes to the ECG waveform in healthy subjects. These are not clinically significant according to the 2009 guidelines and thus have no effect on the clinical specificity of the 12 lead ECG.

Int J Cardiol: 12 Aug 2010; epub ahead of print
Sheppard J, Barker T, Ranasinghe A, Clutton-Brock T, Frenneaux M, Parkes M
Int J Cardiol: 12 Aug 2010; epub ahead of print | PMID: 20701990
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Abstract

New oral anticoagulants and dual antiplatelet therapy: Focus on apixaban.

Pelliccia F, Rollini F, Marazzi G, Greco C, ... Angiolillo DJ, Rosano G
The combination of AF and coronary artery disease not only is a common clinical setting, it is also a complex setting to deal with anticoagulation and antiplatelet therapy, and it is associated with significantly higher mortality rates. Unfortunately, there are no sufficient data available to optimally guide clinical practice in such settings. This review focuses specifically on newer oral anticoagulants (NOACs) associated with dual antiplatelet therapy (DAPT) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). There are no randomized studies comparing vitamin K antagonists and NOACs in patients with AF undergoing PCI either for acute coronary syndromes or for stable patients, i.e. those patients who have an indication to receive DAPT. Moreover, new antiplatelet agents such as ticagrelor and prasugrel have entered the market for acute coronary syndromes. So far, there are no large-scale randomized studies published evaluating these newer antiplatelet agents in patients with AF receiving either vitamin K antagonists or NOACs, adding to the uncertainty on how to use these antithrombotics in combination when both coronary artery disease (unstable or stable patients) and AF converge in a given patient. The lack of large outcome trials and the large number of possible combinations are reflected in the wide variety of practices in the real world. To date, given the lack of data, watchfulness when using NOACs as component of DAPT or triple oral antithrombotic therapy is warranted.

Int J Cardiol: 09 Oct 2016; 225:154-158
Pelliccia F, Rollini F, Marazzi G, Greco C, ... Angiolillo DJ, Rosano G
Int J Cardiol: 09 Oct 2016; 225:154-158 | PMID: 27723533
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Abstract

Predictors of late recurrence of atrial fibrillation after catheter ablation.

Cai L, Yin Y, Ling Z, Su L, ... Zhu J, Zrenner B
Background: To predict the recurrence of atrial fibrillation is important for selecting patients who will be undergoing catheter ablation, several studies respectively evaluated the risk factor of the recurrence of atrial fibrillation post-ablation. Objective: To investigate the factors predicting the recurrence of atrial fibrillation (AF) after catheter ablation. Methods: 186 patients (55.12±12.06years, 123 male) including 161 paroxysmal AF and 25 non-paroxysmal AF who underwent catheter ablation were studied. Clinical datum before and during ablation were recorded, and systematic follow-up was conducted after ablation. Univariate and multivariate analyses were carried out to determine the factors predicting late recurrence of AF (LRAF) which means AF recurrence after 3months. Results: There were 47(25.27%) patients who experienced LRAF. Multivariate Logistic regression analysis was carried out to the parameters that P<0.10 in the univariate analysis, which includes overweight/obesity, metabolic syndrome (MetS), AF categories, duration of AF history, left atrial diameter (LAD), diabetes mellitus, ablation strategies, procedural failure and early recurrence of AF after ablation (ERAF). Ultimately, the results demonstrated that overweight/obesity (OR=4.71, 95% CI 1.71-12.98, P=0.003), MetS (OR=4.41, 95% CI 1.56-12.46, P=0.005), procedural failure (OR=58.34, 95% CI 6.83-498.34, P<0.001), and ERAF (OR=3.18, 95% CI 1.07-9.44, P=0.037) were independent predictors of AF recurrence after ablation. Conclusion: Overweight/obesity, metabolic syndrome, procedural failure and ERAF are independent predictors of late recurrence of atrial fibrillation in this group of patients.

Int J Cardiol: 08 Jul 2011; epub ahead of print
Cai L, Yin Y, Ling Z, Su L, ... Zhu J, Zrenner B
Int J Cardiol: 08 Jul 2011; epub ahead of print | PMID: 21737164
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Abstract

TAPSE: An old but useful tool in different diseases.

Aloia E, Cameli M, D\'Ascenzi F, Sciaccaluga C, Mondillo S
RV function is an important component of overall heart function with prognostic value in predicting symptomatic limitation and outcome in different cardiovascular pathologies. RV longitudinal contraction accounts for the majority of total RV function, up to 80%, as compared to transverse shortening. Calculation of RV volume and RV ejection fraction (RVEF) remains hampered by the complex RV geometry and we lack a good geometric model allowing the calculation of right ventricular ejection fraction; secondly, the large apical trabeculations of the right ventricle make the endocardial delineation more difficult to obtain than for the left ventricle. To notice, the gold standard method for the assessment of the chamber (MRI) is resource intensive and cannot be employed in many settings. Considering these problems, multiple parameters have been developed for the evaluation of RV systolic function: tricuspid annular plane systolic excursion (TAPSE), systolic excursion velocity (S\'), and longitudinal strain by speckle tracking.

Int J Cardiol: 10 Oct 2016; 225:177-183
Aloia E, Cameli M, D'Ascenzi F, Sciaccaluga C, Mondillo S
Int J Cardiol: 10 Oct 2016; 225:177-183 | PMID: 27728861
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Abstract

Myocardial hypertrophy after pulmonary regurgitation and valve implantation in pigs.

Smith J, Goetze JP, Søndergaard L, Kjaergaard J, ... Hassager C, Andersen CB
Background: Patients may suffer from right ventricular (RV) failure and malignant cardiac arrhythmias after late pulmonary valve replacement correcting pulmonary regurgitation (PR). But the underlying mechanisms of the refractory arrhythmias are not well understood. Methods: The aim of present study was to characterize the RV myocardium after percutaneous pulmonary valve implantation (PPVI) in a porcine model after severe PR for 3months. RV histology was evaluated with morphometric methods and RV function was assessed with electrophysiology, echocardiography, and biochemical measures: The results were compared with age-matched sham-operated animals. Results: At euthanasia, RV weight was increased compared to sham-animals, median 127g (115-137) vs. 71g (69.5-76.5), p=0.0007. RV myocyte diameters corrected for individual variation with the RV/LV ratio were enlarged, 1.06 (1.02-1.13) vs. 0.84 (0.80-0.91), p=0.0006. There were no excess collagen tissue (RV/LV ratio), p=0.77. Electrophysiological stimulation resulted in RV arrhythmia in 67% of the animals compared to 25% in the sham-operated animals, but this difference was not statistically significant, p=0.28. Echocardiography revealed geometrical dilation in end-systolic RV area, mean±SD, 11.8±4.9cm(2) vs. 6.0±3.5cm(2), p=0.05, and end-diastolic area, 23.3±10.4cm(2) vs. 12.7±2.5cm(2), p=0.08. RV anterior free wall thickness was not increased, 0.7±0.2cm vs. 0.7±0.1cm, p=0.66. Echocardiographic functional parameters and plasma natriuretic peptides were unchanged. Conclusions: The RV does not completely recover after three months of PR with persistent myocardial hypertrophy one month after PPVI. Future studies should address whether RV chamber and cellular hypertrophy, without fibrosis or interventional scar tissue, may be substrate for arrhythmia.

Int J Cardiol: 17 Mar 2011; epub ahead of print
Smith J, Goetze JP, Søndergaard L, Kjaergaard J, ... Hassager C, Andersen CB
Int J Cardiol: 17 Mar 2011; epub ahead of print | PMID: 21411159
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Abstract

Stress cardiomyopathy: Is it limited to Takotsubo syndrome? Problems of definition.

Sarapultsev PA, Sarapultsev AP
In 2006, Takotsubo syndrome (TTC) was described as a distinct type of stress-induced cardiomyopathy (stress cardiomyopathy). However, when thinking about Takotsubo cardiomyopathy from the viewpoints of the AHA and ESC classifications, 2 possible problems may arise. The first potential problem is that a forecast of disease outcome is lacking in the ESC classification, whereas the AHA only states that \'outcome is favorable with appropriate medical therapy\'. However, based on the literature data, one can make a general conclusion that occurrence of myocardial lesions in TTC (i.e., myocardial fibrosis and contraction-band necrosis) causes the same effects as in other diseases with similar levels of myocardial damage and should not be considered to have a lesser impact on mortality. To summarise, TTC can cause not only severe complications such as pulmonary oedema, cardiogenic shock, and dangerous ventricular arrhythmias, but also damage to the myocardium, which can result in the development of potentially fatal conditions even after the disappearance of LV apical ballooning. The second potential problem arises from the definition of TTC as a stress cardiomyopathy in the AHA classification. In fact, the main factors leading to TTC are stress and microvascular anginas, since, as has been already discussed, coronary spasm can cause myocardium stunning, resulting in persistent apical ballooning. Thus, based on this review, 3 distinct types of stress cardiomyopathies exist (variant angina, microvascular angina, and TTC), with poor prognosis. Adding these diseases to the classification of cardiomyopathies will facilitate diagnosis and preventive prolonged treatment, which should include intensive anti-stress therapy.

Int J Cardiol: 16 Jul 2016; 221:698-718
Sarapultsev PA, Sarapultsev AP
Int J Cardiol: 16 Jul 2016; 221:698-718 | PMID: 27424315
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Abstract

Surgical management of infected cardiac implantable electronic devices.

Chaudhry UA, Harling L, Ashrafian H, Athanasiou C, ... Kokotsakis J, Athanasiou T
The growing use of cardiac implantable electronic devices (CIED) has led to infections requiring intervention. These are traditionally managed using a percutaneous transvenous approach to fully extract the culpable leads. Indications for such strategies are well-established and range from simple traction to the use of powered extraction tools including laser sheaths. Where such attempts fail, or if there are further complications, then there may be need for a cardiothoracic surgical approach. Limited evidence is currently available on the merits of individual strategies, and these are mainly drawn from case reports or series. Most utilise cardiopulmonary bypass, cardioplegic arrest and entry within the right atrium to allow direct visualisation of any vegetation and safely explant all CIED components whilst avoiding perforation, valvular and paravalvular damage. In this review, we describe a number of these and the unique challenges faced by surgeons when attempting to extract CIED. It is clear that future work should concentrate on creating clear consensus and guidelines on indications, risks and measures of efficacy outcomes for various surgical techniques.

Int J Cardiol: 21 Nov 2015; 203:714-721
Chaudhry UA, Harling L, Ashrafian H, Athanasiou C, ... Kokotsakis J, Athanasiou T
Int J Cardiol: 21 Nov 2015; 203:714-721 | PMID: 26590887
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Abstract

Brugada syndrome and Brugada phenocopy. The importance of a differential diagnosis.

Dendramis G
To date Brugada syndrome (BrS) is considered a primary electrical heart disease and the diagnosis is based on precise clinical and electrocardiographic features. Many other diseases and conditions can lead to a Brugada-like ECG pattern but the vast majority of patients with BrS possess a structurally normal heart, which is consistent with the notion that this is a primary electrical heart disease. Presently, the terminology used in the literature to describe Brugada type 1 ECG pattern induced in patients without BrS is diverse and variable. Brugada phenocopies (BrP) are clinical entities that present with identical ECG patterns to those of true BrS but are elicited by various other clinical circumstances. They form a group of heterogeneous conditions that are perhaps the most difficult to differentiate from true congenital BrS due to identical ECG patterns and recently has been proposed an updated classification of conditions that may induce BrP and many criteria useful to differentiate BrP from BrS. A systematic diagnostic approach is crucial to avoid diagnostic errors that involve expenditure of time and resources, but above all it is useful to avoid to send patients without a real BrS to inopportune diagnostic and therapeutic paths that are sometimes burdened by considerable risks.

Int J Cardiol: 27 Feb 2016; 210:25-27
Dendramis G
Int J Cardiol: 27 Feb 2016; 210:25-27 | PMID: 26922708
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Abstract

Calcium sensitizers: What have we learned over the last 25years?

Pollesello P, Papp Z, Papp JG
The use of inotropes for correcting hemodynamic dysfunction in patients with congestive heart failure has been described over many decades. Drugs such as cardiac glycosides, cathecolamines, phosphodiestherase inhibitors, and calcium sensitizers have been in turn proposed. However, the number of new chemical entities in this therapeutic field has been surprisingly low, and the current selection of drugs is limited. One of the paradigm shifts in the discovery for new inotropes was to focus on \'calcium sensitizers\' instead of \'calcium mobilizers\'. This was designed to lead to the development of safer inotropes, devoid of the complications that arise due to increased intracellular calcium levels. However, only three such calcium sensitizers have been fully developed over the latest 30years. Moreover, two of these, levosimendan and pimobendan, have multiple molecular targets and other pharmacologic effects in addition to inotropy, such as peripheral vasodilation. More recently, omecamtiv mecarbil was described, which is believed to have a pure inotropy action that is devoid of pleiotropic effects. When the clinical data of these three calcium sensitizers are compared, it appears that the less pure inotropes have the cutting edge over the purer inotrope, due to additional effects during the treatment of a complex syndrome such as acute congested heart failure. This review aims to answer the question whether calcium sensitization per se is a sufficient strategy for bringing required clinical benefits to patients with heart failure. This review is dedicated to the memory of Heimo Haikala, a true and passionate innovator in this challenging field.

Int J Cardiol: 17 Nov 2015; 203:543-548
Pollesello P, Papp Z, Papp JG
Int J Cardiol: 17 Nov 2015; 203:543-548 | PMID: 26580334
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Impact:
Abstract

Statin non-adherence and residual cardiovascular risk: There is need for substantial improvement.

Banach M, Stulc T, Dent R, Toth PP
Although statin therapy has proven to be the cornerstone for prevention and treatment of cardiovascular disease (CVD), there are many patients for whom long-term therapy remains suboptimal. The aims of this article are to review the current complex issues associated with statin use and to explore when novel treatment approaches should be considered. Statin discontinuation as well as adherence to statin therapy remain two of the greatest challenges for lipidologists. Evidence suggests that between 40 and 75% of patients discontinue their statin therapy within one year after initiation. Furthermore, whilst the reasons for persistence with statin therapy are complex, evidence shows that low-adherence to statins negatively impacts clinical outcomes and residual CV risk remains a major concern. Non-adherence or lack of persistence with long-term statin therapy in real-life may be the main cause of inadequate low density lipoprotein cholesterol lowering with statins. There is a large need for the improvement of the use of statins, which have good safety profiles and are inexpensive. On the other hand, in a non-cost-constrained environment, proprotein convertase subtilisin/kexin type 9 inhibitors should arguably be used more often in those patients in whom treatment with statins remains unsatisfactory.

Int J Cardiol: 10 Oct 2016; 225:184-196
Banach M, Stulc T, Dent R, Toth PP
Int J Cardiol: 10 Oct 2016; 225:184-196 | PMID: 27728862
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Abstract

Overexpression of cAMP-response element modulator causes abnormal growth and development of the atrial myocardium resulting in a substrate for sustained atrial fibrillation in mice.

Kirchhof P, Marijon E, Fabritz L, Li N, ... Hatem S, Müller FU
Background AND Methods: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. The substrate of AF is composed of a complex interplay between structural and functional changes of the atrial myocardium often preceding the occurrence of persistent AF. However, there are only few animal models reproducing the slow progression of the AF substrate to the spontaneous occurrence of the arrhythmia. Transgenic mice (TG) with cardiomyocyte-directed expression of CREM-IbΔC-X, an isoform of transcription factor CREM, develop atrial dilatation and spontaneous-onset AF. Here we tested the hypothesis that TG mice develop an arrhythmogenic substrate preceding AF using physiological and biochemical techniques. Results: Overexpression of CREM-IbΔC-X in young TG mice (<8weeks) led to atrial dilatation combined with distension of myocardium, elongated myocytes, little fibrosis, down-regulation of connexin 40, loss of excitability with a number of depolarized myocytes, atrial ectopies and inducibility of AF. These abnormalities continuously progressed with age resulting in interatrial conduction block, increased atrial conduction heterogeneity, leaky sarcoplasmic reticulum calcium stores and the spontaneous occurrence of paroxysmal and later persistent AF. This distinct atrial remodelling was associated with a pattern of non-regulated and up-regulated marker genes of myocardial hypertrophy and fibrosis. Conclusions: Expression of CREM-IbΔC-X in TG hearts evokes abnormal growth and development of the atria preceding conduction abnormalities and altered calcium homeostasis and the development of spontaneous and persistent AF. We conclude that transcription factor CREM is an important regulator of atrial growth implicated in the development of an arrhythmogenic substrate in TG mice.

Int J Cardiol: 18 Nov 2011; epub ahead of print
Kirchhof P, Marijon E, Fabritz L, Li N, ... Hatem S, Müller FU
Int J Cardiol: 18 Nov 2011; epub ahead of print | PMID: 22093963
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Abstract

Unfractionated heparin or low-molecular-weight heparin in the elderly.

Dorobantu M, Bogdan S
With the ageing of the general population, clinicians are facing with increased frequency the challenge of administering parenteral anti-coagulation therapy in the elderly, the main indications being venous thromboembolism (VTE), acute coronary syndromes (ACS), atrial fibrillation and bridging therapy. Assessing the risk/benefit ratio is always difficult in this category of patients, because of the higher risk for hemorrhagic events, although in most cases the benefit outweighs the risk, especially in the setting of VTE. The development of early invasive strategies for treating ACS has improved outcomes, while reducing the need for prolonged anticoagulation. For ST-segment elevation acute myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) is the mainstay treatment with well documented benefits in terms of mortality reduction regardless of the patient\'s age. However, evidence is less strong regarding early invasive treatment for over 75-year old Non-STEMI patients, resulting in a significant percentage being treated conservatively, including parenteral anticoagulation. This review will focus on the use of parenteral anticoagulation (unfractionated or low-molecular weight heparin) in older patients. We will analyze current guidelines-based parenteral anticoagulation indications, while focusing on specific considerations in the elderly, such as: frailty and comorbidities, pharmacokinetics, the hemorrhagic risk and available clinical evidence. The goal is to offer a comprehensive tool for the clinician managing parenteral anticoagulation in older patients.

Int J Cardiol: 24 Aug 2016; epub ahead of print
Dorobantu M, Bogdan S
Int J Cardiol: 24 Aug 2016; epub ahead of print | PMID: 27558233
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Abstract

A guide for identification and continuing care of adult congenital heart disease patients in primary care.

Ellison S, Lamb J, Haines A, O\'Dell S, ... Vaughan J, Mahadevan VS
Background: Surgical and other advances in the treatment and care of congenital heart disease have resulted in a significant increase in the number of adults with congenital heart disease (ACHD), many of whom have no regular cardiology follow-up. Optimised care for ACHD patients requires continuity of specialist and shared care and education of practitioners and patients. The challenges for managing ACHD were identified by a Health Needs Assessment in the North West and are addressed within the UK Department of Health\'s ACHD Commissioning Guide. MATERIALS AND Methods: An ACHD model of care was recommended in the North West of England and developed by the three North West Cardiac & Stroke Networks. Within this, a Task Group focused on the role of primary care in the identification and continuing care of ACHD patients. A feasibility study demonstrated that existing diagnostic Read Codes can identify ACHD patients on general practice registers. An ACHD Toolkit was developed to provide algorithms to guide the appropriate management of ACHD patients through primary, secondary and/or specialist ACHD care and to improve education/knowledge amongst primary care staff about ACHD and its wider implications. Results: Early findings during the development of this Toolkit illustrate a wide disparity of provision between current and optimal management strategies. Patients lost to follow-up have already been identified and their management modified. Conclusions: By focusing on identifying ACHD patients in primary care and organising/delivering ACHD services, the ACHD Toolkit could help to improve quality, timeliness of care, patient experience and wellbeing.

Int J Cardiol: 27 Jun 2011; epub ahead of print
Ellison S, Lamb J, Haines A, O'Dell S, ... Vaughan J, Mahadevan VS
Int J Cardiol: 27 Jun 2011; epub ahead of print | PMID: 21703700
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Abstract

Relationship of non-cardiac biomarkers with periprocedural myocardial injury in patients undergoing percutaneous coronary intervention.

Zeng RX, Li JJ, Liao PD, Zhang MZ
percutaneous coronary intervention (PCI) is one of the dominant methods for revascularization in patient with coronary artery disease (CAD), which accompanied with high incidence of periprocedural myocardial injury (PMI) evaluated by postprocedural cardiac biomarker elevation. For the convenience of risk stratification of PMI following PCI, the aim of present review provides a unique opportunity to summarize the relationship of non-cardiac biomarkers with PMI by extensively searching in the MEDLINE to identify all the relevant studies. In conclusion, we found that PCI related PMI might be correlated positively to those non-cardiac biomarkers such as low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, total cholesterol, triglyceride, the ratios of LDL-C to high-density lipoprotein cholesterol (HDL-C), the ratios of HDL-C to apolipoprotein A-I, the ratio of eicosapentaenoic acid to arachidonic acid, lectin-like oxidized low-density lipoprotein receptor-1, C-reactive protein, high on-treatment platelet reactivity, platelet-monocyte aggregates, N-term pro-B-type natriuretic peptide, hemoglobin and albuminuria. Inversely, no relationships of PMI with those non-cardiac biomarkers such as mean platelet volume, platelet distribution width, platelet-larger cell ratio, uric acid, eosinophils count and the genetic variant of methylenetetrahydrofolate reductase (MTHFR) 677 C>T polymorphism. Moreover, there were controversial associations between PMI and those non-cardiac biomarkers such as high-density lipoprotein cholesterol, glycosylated hemoglobin, homocysteine and the polymorphism Leu33Pro of platelet glycoprotein IIbIIIa. However, almost all studies failed to provide definite mechanism of its findings, and further reaches are needed to focus on the potential mechanisms of association between non-cardiac biomarkers and PMI related to PCI.

Int J Cardiol: 17 Jul 2016; 221:726-733
Zeng RX, Li JJ, Liao PD, Zhang MZ
Int J Cardiol: 17 Jul 2016; 221:726-733 | PMID: 27428312
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Abstract

Normal and abnormal development of pulmonary veins: State of the art and correlation with clinical entities.

Douglas YL, Jongbloed MR, Deruiter MC, Gittenberger-de Groot AC
Interest for the pulmonary veins has increased in the past decade after the potential arrhythmogenicity of the myocardial sleeve surrounding these structures has been recognized. Furthermore, there are several clinical entities, such as anomalous connection pattern and pulmonary vein stenosis, that are related to abnormal pulmonary vein development. In this review, we will describe current literature and aim to elucidate and reorganize current opinions on normal and abnormal pulmonary vein development in relation to clinical (management of) diseases. Several unresolved questions will be addressed, as well as current conceptual controversies. First, a general overview of development of structures at the venous pole of the heart, including normal development of the pulmonary vein from a primitive Anlage, will be provided. Recent insights indicate an important contributory role of the mesoderm behind the heart, the so-called second heart field, to this area. Subsequently, the formation of a myocardial and smooth muscle vascular wall of the pulmonary veins and the left atrium is described, as well as current insights in the mechanisms involved in the differentiation of these different cell types in this area. Next, developmental concepts of normal pulmonary venous drainage patterns are reviewed, and an overview is provided of clinical entities related to abnormal development at several anatomical levels. Lastly, attention is paid to arrhythmogenesis in relation to pulmonary vein development, as well the consequences for clinical management.

Int J Cardiol: 02 Aug 2010; epub ahead of print
Douglas YL, Jongbloed MR, Deruiter MC, Gittenberger-de Groot AC
Int J Cardiol: 02 Aug 2010; epub ahead of print | PMID: 20674049
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Abstract

Potential beneficial effect of some adipokines positively correlated with the adipose tissue content on the cardiovascular system.

Sawicka M, Janowska J, Chudek J
Obesity is a risk factor of cardiovascular diseases. However, in the case of heart failure, obese and overweight patients have a more favourable prognosis compared to patients who have a normal body weight. This phenomenon is referred to as the "obesity paradox," and it is explained by, among others, a positive effect of adipokines produced by adipose tissue, particularly by the tissue located in the direct vicinity of the heart and blood vessels. The favourable effect on the cardiovascular system is mostly associated with adiponectin and omentin, but the levels of these substances are reduced in obese patients. Among the adipokines which levels are positively correlated with the adipose tissue content, favourable activity is demonstrated by apelin, progranulin, chemerin, TNF-α (tumour necrosis factor-)α, CTRP-3 (C1q/tumour necrosis factor (TNF) related protein), leptin, visfatin and vaspin. This activity is associated with the promotion of regeneration processes in the damaged myocardium, formation of new blood vessels, reduction of the afterload, improvement of metabolic processes in cardiomyocytes and myocardial contractile function, inhibition of apoptosis and fibrosis of the myocardium, as well as anti-inflammatory and anti-atheromatous effects. The potential use of these properties in the treatment of heart failure and ischaemic heart disease, as well as in pulmonary hypertension, arterial hypertension and the limitation of the loss of cardiomyocytes during cardioplegia-requiring cardiosurgical procedures, is studied. The most advanced studies focus on analogues of apelin and progranulin.

Int J Cardiol: 10 Aug 2016; 222:581-589
Sawicka M, Janowska J, Chudek J
Int J Cardiol: 10 Aug 2016; 222:581-589 | PMID: 27513655
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Abstract

Cardiac cachexia: hic et nunc: "hic et nunc" - here and now.

Loncar G, Springer J, Anker M, Doehner W, Lainscak M
Cardiac cachexia (CC) is the clinical entity at the end of chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. Better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick-up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF.

Int J Cardiol: 06 Nov 2015; epub ahead of print
Loncar G, Springer J, Anker M, Doehner W, Lainscak M
Int J Cardiol: 06 Nov 2015; epub ahead of print | PMID: 26545926
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Abstract

Comparing exercise training modalities in heart failure: A systematic review and meta-analysis.

Cornelis J, Beckers P, Taeymans J, Vrints C, Vissers D
Exercise training (ET) is suggested to improve exercise capacity, prognosis, quality of life (QOL) and functional modifications of the heart in patients with heart failure (HF). However, it is not clear which modality is best. In order to assess the effectiveness of different ET modalities on prognostic cardiopulmonary exercise test (CPET) parameters, QOL and left ventricular remodeling, a systematic review and meta-analysis was performed. Randomized clinical trials (RCTs) were selected in three databases. The primary outcome data were peak oxygen uptake, ventilation over carbon dioxide slope, oxygen uptake efficiency slope, exercise oscillatory ventilation, rest and peak pulmonary end-tidal CO2. Secondary variables were QOL, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD). Twenty RCTs (n=811) met the a priori stated inclusion criteria. Studies were categorized into four different groups: "interval training (IT1) versus combined interval and strength training (IT1S)" (n=156), "continuous training (CT1) versus combined continuous and strength training (CT1S)" (n=130), "interval training (IT2) versus continuous training (CT2)" (n=501) and "continuous training (CT3) versus strength training (S3)" (n=24). No significant random effects of exercise modality were revealed assessing the CPET parameters. There was a significant improvement in QOL applying CT1S (P<0.001). Comparing IT2 with CT2, LVEDD and LVEF were significantly improved favoring IT2 (P<0.001). There is some evidence to support that interval training is more effective to improve LVEF and LVEDD. The fact that patients with HF are actively involved in any kind of ET program seems sufficient to improve the prognosis, QOL and anatomic function.

Int J Cardiol: 18 Jul 2016; 221:867-876
Cornelis J, Beckers P, Taeymans J, Vrints C, Vissers D
Int J Cardiol: 18 Jul 2016; 221:867-876 | PMID: 27434363
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Abstract

Vascular remodeling in pulmonary arterial hypertension: Multiple cancer-like pathways and possible treatment modalities.

Sakao S, Tatsumi K
Most patients with severe pulmonary arterial hypertension (PAH) demonstrate persistent structural alterations in small pulmonary arterioles at the time of diagnosis, including marked proliferation of pulmonary artery endothelial cells (ECs), smooth muscle cells (SMCs) and fibroblasts. Rai et al. have recently proposed a paradigm shift to explain the pathobiology of small vessel disease in severe PAH patients as a quasi-neoplastic process. Indeed, the vascular lesions of patients with severe PAH exhibit some cancer-like characteristics: decreased population of apoptotic cells and overexpression of antiapoptotic proteins. Nevertheless they lack the capability for tissue invasion and metastasis. The article reviews pathomechanisms of vascular lesions in PAH comparing them with each of the cancer defining mechanisms and indicates the potential utility of antineoplastic drugs as antiproliferative treatment in PAH. PDGF has been identified as a novel potential therapeutic target and the successful treatment of experimental PAH with a PDGF receptor tyrosine kinase inhibitor has been demonstrated recently. These findings justify further clinical trials concerning thyrosine kinase inhibitors as future PAH therapies. However, the drugs currently developed for malignant neoplasms to target neoplastic proliferation should be tested carefully in PAH patients due to their cardiac and pulmonary toxicity.

Int J Cardiol: 09 Aug 2010; epub ahead of print
Sakao S, Tatsumi K
Int J Cardiol: 09 Aug 2010; epub ahead of print | PMID: 20692712
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Abstract

Echocardiographic assessment of the right ventricle: Impact of the distinctly load dependency of its size, geometry and performance.

Dandel M, Hetzer R
Right ventricular (RV) size, shape and function are distinctly load-dependent and pulmonary load is an important determinant of RV function in patients with congestive heart failure (CHF) due to primary impaired left ventricular function and in those with pre-capillary pulmonary hypertension (PH). In a pressure overloaded RV, not only dilation and aggravation of tricuspid regurgitation, but also systolic dysfunction leading to RV failure (RVF) can occur already before the development of irreversible alterations in RV myocardial contractility. This explains RV ability for reverse remodeling and functional improvement in patients with post-capillary and pre-capillary PH of a different etiology, after normalization of loading conditions. There is increasing evidence that RV evaluation by echocardiography in relation with its loading conditions can improve the decision-making process and prognosis assessments in clinical praxis. Recent approaches to evaluate the RV in relation with its actual loading conditions by echo-derived composite variables which either incorporate a certain functional parameter (i.e. tricuspid annulus peak systolic excursion, stroke volume, RV end-systolic volume index, velocity of myocardial shortening) and load, or incorporate measures which reflect the relationship between RV load and RV dilation, also taking the right atrial pressure into account (i.e. "load adaptation index"), appeared particularly suited and therefore also potentially useful for evaluation of RV contractile function. Special attention is focused on the usefulness of RV echo-evaluation in relation to load for proper decision making before ventricular assist-device implantation in patients with CHF and for optimal timing of listing procedures to transplantation in patients with end-stage pre-capillary PH.

Int J Cardiol: 29 Jul 2016; 221:1132-1142
Dandel M, Hetzer R
Int J Cardiol: 29 Jul 2016; 221:1132-1142 | PMID: 27474972
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Abstract

Myocardial extraction of intracellular magnesium and atrial fibrillation after coronary surgery.

Abdel-Massih TE, Sarkis A, Sleilaty G, El Rassi I, ... Ashoush R, Jebara V
Background: The effects of magnesium loading on the incidence of atrial fibrillation following coronary artery bypass graft surgery (CAGB) are equivocal. None of the previous studies assessed the influence of myocardial extraction of magnesium in these settings. The current trial aims to elucidate whether the incidence of atrial fibrillation following CABG is affected by the preoperative rate of myocardial extraction of magnesium. Methods: The ethical committee approved the study protocol. 113 patients (94 male, mean age 63±11years) planned for elective CABG surgery under normothermic cardiopulmonary bypass were prospectively included. Preoperative independent variables included preoperative treatment, electrocardiographic abnormalities, left ventricular ejection fraction estimation, left atrial size, creatinine clearance and assays of plasma and intracellular magnesium, calcium, albumin, potassium and ionized calcium, drawn preoperatively from the coronary sinus and the aortic root. The covariates - including the rate of myocardial extraction of magnesium - were entered in a logistic regression model to predict the odds of atrial fibrillation. Results: The incidence of post operative atrial fibrillation was 16%. A rate of myocardial extraction of intracellular magnesium ≥7% increases fivefold the multivariate risk of postoperative atrial fibrillation (p<.01). Advanced age was also significantly associated to postoperative atrial fibrillation. Conclusions: This study suggests that a preoperative rate of myocardial extraction of intracellular magnesium ≥7% could be a new and a potent predictive factor for postoperative atrial fibrillation.

Int J Cardiol: 09 May 2011; epub ahead of print
Abdel-Massih TE, Sarkis A, Sleilaty G, El Rassi I, ... Ashoush R, Jebara V
Int J Cardiol: 09 May 2011; epub ahead of print | PMID: 21550673
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Abstract

A comparison of ST elevation versus non-ST elevation myocardial infarction outcomes in a large registry database Are non-ST myocardial infarctions associated with worse long-term prognoses?

Polonski L, Gasior M, Gierlotka M, Osadnik T, ... Tendera M, on behalf of the PL-ACS Registry Pilot Group
Background: Prognoses in STEMI and NSTEMI beyond one year from onset remain unclear. We aimed to compare the treatments and the two-year outcomes in patients with myocardial infarction (MI) enrolled at the Polish Registry of Acute Coronary Syndromes (PL-ACS). Methods: A total of 13,441 patients with MI (8250 with STEMI, and 5191 with NSTEMI) underwent medical care between October 2003 and June 2005 in the Silesia region (4.8 million inhabitants). The events analyzed were death, MI, stroke and percutaneous (PCI) or surgical (CABG) revascularization. Results: After two years, NSTEMI was associated with a higher incidence of death (hazard ratio (HR) of 1.09 (95% confidence interval (CI) 1.02-1.17, p<0.0001)); a higher incidence of reinfarction, stroke, CABG and a lower rate of PCI. Adjustments for baseline characteristics and treatment strategy (invasive vs. non-invasive) reversed the HR for mortality and eliminated the difference in MI and stroke. The adjusted HR for mortality was 0.76 (95% CI, 0.71-0.83, p<0.0001). STEMI and NSTEMI patients treated non-invasively were older and showed higher incidences of diabetes, obesity, pulmonary edema and cardiogenic shock than their invasively treated counterparts. Invasively treated patients received aspirin, beta-blockers, ACE inhibitors and statins more often during hospitalization and at discharge. Conclusions: The unadjusted long-term prognosis was worse in NSTEMI. After adjustment for the baseline characteristics and treatment strategy, the long-term prognosis was worse in STEMI. Patients with MI treated invasively showed more favorable clinical characteristics and received guideline-recommended therapy more often than patients who did not undergo invasive treatment.

Int J Cardiol: 05 Aug 2010; epub ahead of print
Polonski L, Gasior M, Gierlotka M, Osadnik T, ... Tendera M, on behalf of the PL-ACS Registry Pilot Group
Int J Cardiol: 05 Aug 2010; epub ahead of print | PMID: 20684999
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Abstract

Validation of an animal model of right ventricular dysfunction and right bundle branch block to create close physiology to postoperative tetralogy of Fallot.

Thambo JB, Roubertie F, De Guillebon M, Labrousse L, ... Dos Santos P, Bordachar P
Background: In the past 5years a few number of studies and case reports have come out focusing on biventricular (BiV) stimulation for treatment of congenital heart disease related ventricular dysfunction. The few available studies include a diverse group of pathophysiological entities ranging from a previously repaired tetralogy of Fallot (TOF) to a functional single ventricle anatomy. Patient\'s status is too heterogeneous to build important prospective study. To well understand the implication of prolonged electromechanical dyssynchrony we performed a chronic animal model that mimics essential parameters of postoperative TOF. Methods: Significant pulmonary regurgitation, mild stenosis, as well as right ventricular outflow tract (RVOT) scars were induced in 15 piglets to mimic repaired TOF. 4months after hemodynamics and dyssynchrony parameters were compared with a control group and with a population of symptomatic adult with repaired TOF. Results: Comparing the animal model with the animal control group on echocardiography, RV dilatation, RV and LV dysfunction, broad QRS complex and dyssynchrony were observed on the animal model piglets. Moreover, epicardial electrical mapping showed activation consistent with a right bundle branch block. The animal models displayed the same pathophysiological parameters as the post TOF repair patients in terms of QRS duration, pulmonary regurgitation biventricular dysfunction and dyssynchrony. Conclusion: This chronic swine model mimics electromechanical ventricular activation delay, RV and LV dysfunction, as in adult population of repair TOF. It does appear to be a very useful and interesting model to study the implication of dyssynchrony and the interest of resynchronization therapy in TOF failing ventricle.

Int J Cardiol: 20 Sep 2010; epub ahead of print
Thambo JB, Roubertie F, De Guillebon M, Labrousse L, ... Dos Santos P, Bordachar P
Int J Cardiol: 20 Sep 2010; epub ahead of print | PMID: 20851478
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Abstract

Analysis of liver metabolism in a rat model of heart failure.

Kato T, Niizuma S, Inuzuka Y, Kawashima T, ... Kimura T, Shioi T
Background: Cachexia, namely body wasting, is a common complication in cases of congestive heart failure (CHF). Although, neurohumoral and immune abnormalities are associated with the condition, precisely how the imbalance of catabolism and anabolism is responsible for the wasting process is not known. Methods: We analyzed markers of cachexia in Dahl salt-sensitive rats which show marked hypertension with preserved systolic function at 11weeks and CHF at 17-19weeks of age. We also analyzed the change in hepatic metabolism associated with CHF since liver plays a central role in the systemic regulation of catabolism and anabolism. Results: In CHF rats, a failure to grow was observed and blood hepatic protein levels were decreased associated with increased blood proinflammatory cytokine levels, indicating that Dahl rats serve as a model of cardiac cachexia. Food intake was reduced, and blood sugar and insulin levels were decreased. Despite the apparent fasting condition, blood fatty acid levels were decreased and triglycerides levels were increased. In CHF rats, liver incorporated more glucose, the gene expression related to gluconeogenesis was decreased, the gene expression related to lipogenesis was increased, and the triglyceride content of the liver was increased. The paradoxical production of triglycerides synthesis in fasting rats was associated with a proinflammatory response in liver. Conclusions: The Dahl salt-sensitive rat can be used as a model of cardiac cachexia. The cachexia was associated with abnormal hepatic metabolism that might work as a maladaptive response during the progression of CHF.

Int J Cardiol: 15 Aug 2011; epub ahead of print
Kato T, Niizuma S, Inuzuka Y, Kawashima T, ... Kimura T, Shioi T
Int J Cardiol: 15 Aug 2011; epub ahead of print | PMID: 21839528
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Abstract

Periconceptional tobacco smoking and Xisolated congenital heart defects in the neonatal period.

Karatza AA, Giannakopoulos I, Dassios TG, Belavgenis G, Mantagos SP, Varvarigou AA
Background: Tobacco use in pregnancy is considered a human developmental toxicant and potential teratogen. The aim of the study was to test for a possible association between periconceptional tobacco smoking and congenital heart disease (CHD) in the neonatal period. Methods: Maternal and infant characteristics of 157 neonates diagnosed with CHD at the University of Patras Medical School were collected and were compared with 208 normal neonates (aged 1-28days) that were referred for echocardiography during a specified 3-year period. Results: In neonates with CHD 64 of 157 mothers (40.8%) reported smoking in pregnancy, whereas in the control group 41 of 208 mothers (19.7%) were smokers (p=0.000). Logistic regression analysis with pregestational diabetes, history of influenza-like illness in the first trimester, therapeutic drug exposure in pregnancy, maternal age, parity, family history of CHD, infant gender, prematurity and paternal smoking, as potential confounding factors showed that periconceptional tobacco smoking was associated with increased risk of CHD in the offspring (OR=2.750, 95% CI=1.659-4.476, p=0.00001). The incidence of neonatal heart disease in women who were non-smokers or smoked 1-10 and >/=11 cigarettes per day increased with the level of fetal tobacco exposure (35.8% versus 55.3% versus 64.3%, x(2)-test=20.303, p=0.000), suggesting a dose effect. Conclusions: The results of the study are indicative of an association between periconceptional tobacco exposure and increased risk of CHD in the neonatal period. The potential role of gestational smoking as a risk factor for specific heart defect subgroups requires the conduction of large population based epidemiological studies.

Int J Cardiol: 02 Dec 2009; epub ahead of print
Karatza AA, Giannakopoulos I, Dassios TG, Belavgenis G, Mantagos SP, Varvarigou AA
Int J Cardiol: 02 Dec 2009; epub ahead of print | PMID: 19951824
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Abstract

Prevalence of comorbidities and associated cardiac diseases in patients with valve aortic stenosis. Potential implications for the decision-making process.

Faggiano P, Frattini S, Zilioli V, Rossi A, ... Tomasi C, Cas LD
ObjectiveS: Aortic valve replacement (AVR) is recommended in patients with symptomatic aortic stenosis (AS). However a large number of elderly patients remain untreated because of a high operative risk. The aim of this study was to assess the risk profile of a group of AS patients, evaluating the prevalence of comorbidities and associated cardiac diseases and their impact on therapeutic decisions. Methods: Two-hundred forty consecutive AS patients underwent complete clinical evaluation, in order to define the stenosis severity, the prevalence of several associated cardiac conditions and comorbidities. Furthermore, the treatment choices based on this approach were recorded. Results: Mean age was 78.6±8.93years, 75.5% was ≥75years old, 60% females; 226 patients (94.2%) had symptoms and 54.2% was in NYHA classes III-IV. Valve area <1cm(2) was detected in 81.6% of patients. Both comorbidities and associated cardiac diseases were common; particularly, renal dysfunction was detected by estimated glomerular filtration rate in 52.7%, chronic obstructive lung disease in 25.4%, cerebrovascular/peripheral artery disease in 30.8% and 11.6%, respectively, diabetes in 30%, malignancies (current or previous) in 26.6% of patients. Among associated cardiac diseases, coronary artery disease was detected in 43.7%, LV systolic dysfunction in 28.7%, pulmonary hypertension in 67%, at least moderate mitral regurgitation in 32.5% and porcelain aorta in 7.5% of patients. Fourteen asymptomatic patients (pts) (5.9%) remained in follow-up, 77 (32%) underwent surgical AVR, 64 (26.7%) underwent transcatheter valve implantation, 28 (11.6%) underwent balloon valvuloplasty and 57 (23.8%), despite symptoms, remained on medical therapy alone. Conclusions: Comorbidities and coexisting cardiac diseases are very common in AS and may strongly influence the decision-making process.

Int J Cardiol: 07 Mar 2011; epub ahead of print
Faggiano P, Frattini S, Zilioli V, Rossi A, ... Tomasi C, Cas LD
Int J Cardiol: 07 Mar 2011; epub ahead of print | PMID: 21376407
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Abstract

Brain natriuretic peptide: Much more than a biomarker.

Calzetta L, Orlandi A, Page C, Rogliani P, ... Cazzola M, Matera MG
Brain natriuretic peptide (BNP) modulates several biological processes by activating the natriuretic peptide receptor A (NPR-A). Atria and ventricles secrete BNP. BNP increases natriuresis, diuresis and vasodilatation, thus resulting in a decreased cardiac workload. BNP and NT-proBNP, which is the biologically inactive N-terminal portion of its pro-hormone, are fast and sensitive biomarkers for diagnosing heart failure. The plasma concentrations of both BNP and NT-proBNP also correlate with left ventricular function in patients with acute exacerbation of COPD, even without history of heart failure. Several studies have been conducted in vitro and in vivo, both in animals and in humans, in order to assess the potential role of the NPR-A activation as a novel therapeutic approach for treating obstructive pulmonary disorders. Unfortunately, these studies have yielded conflicting results. Nevertheless, further recent specific studies, performed in ex vivo models of asthma and COPD, have confirmed the bronchorelaxant effect of BNP and its protective role against bronchial hyperresponsiveness in human airways. These studies have also clarified the intimate mechanism of action of BNP, represented by an autocrine loop elicited by the activation of NPR-A, localized on bronchial epithelium, and the relaxant response of the surrounding ASM, which does not expresses NPR-A. This review explores the teleological activities and paradoxical effects of BNP with regard to chronic obstructive respiratory disorders, and provides an excursus on the main scientific findings that explain why BNP should be considered much more than a biomarker.

Int J Cardiol: 21 Jul 2016; 221:1031-1038
Calzetta L, Orlandi A, Page C, Rogliani P, ... Cazzola M, Matera MG
Int J Cardiol: 21 Jul 2016; 221:1031-1038 | PMID: 27447810
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Abstract

Ivabradine in chronic stable angina: Effects by and beyond heart rate reduction.

Camici PG, Gloekler S, Levy BI, Skalidis E, ... Vardas P, Heusch G
Heart rate plays a major role in myocardial ischemia. A high heart rate increases myocardial performance and oxygen demand and reduces diastolic time. Ivabradine reduces heart rate by inhibiting the If current of sinoatrial-node cells. In contrast to beta-blockers, ivabradine has no negative inotropic and lusitropic effect for a comparable heart rate reduction. Consequently, diastolic duration is increased with ivabradine compared to beta-blockers. This has potential consequences on coronary blood flow since compression of the vasculature by the surrounding myocardium during systole impedes flow and coronary blood flow is mainly diastolic. Moreover, ivabradine does not unmask alpha-adrenergic vasoconstriction and, unlike beta-blockers, maintains coronary dilation during exercise. In comparison with beta-blockers, ivabradine increases coronary flow reserve and collateral perfusion promoting the development of coronary collaterals. Ivabradine attenuates myocardial ischemia and its consequences even in the absence of heart rate reduction, possibly through reduced formation of reactive oxygen species. In conclusion, ivabradine differs from other anti-anginal agents by improving coronary blood flow and by additional pleiotropic effects. These properties make ivabradine an effective anti-anginal and anti-ischemic agent for the treatment of patients with coronary artery disease.

Int J Cardiol: 21 Apr 2016; 215:1-6
Camici PG, Gloekler S, Levy BI, Skalidis E, ... Vardas P, Heusch G
Int J Cardiol: 21 Apr 2016; 215:1-6 | PMID: 27104917
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Abstract

Defining and refining indications for transcatheter pulmonary valve replacement in patients with repaired tetralogy of Fallot: Contributions from anatomical and functional imaging.

Tretter JT, Friedberg MK, Wald RM, McElhinney DB
Transcatheter pulmonary valve replacement (TPVR) is an important treatment option in repaired tetralogy of Fallot (TOF) and right ventricular outflow tract (RVOT) dysfunction. Indications for timing of TPVR are extrapolated from surgical pulmonary valve replacement guidelines, which are themselves controversial as published evidence is scarce and expert opinion therefore prevails. We review current indications for PVR following TOF repair, focusing on those for TPVR specifically, and discuss anatomical and functional considerations as these pertain to determination of candidacy for TPVR. Hemodynamic assessment surrounding PVR has focused on assessment of the right ventricle (RV) size and systolic function, with the goal of intervening in the asymptomatic patient prior to the development of irreversible RV deterioration and right heart failure. The impact of abnormal RV mechanics on the LV has been appreciated, with the assessment of LV function assuming higher priority in decision-making regarding possible PVR. In addition to the standard volumetric assessment, evaluation with indices of myocardial wall strain, tissue velocities, diastology, and ventricular response to exercise is emerging as tools with potential to further refine timing of PVR. We conclude that, at present, current evidence, although limited, supports a more aggressive approach in those who meet inclusion for TPVR in patients with repaired TOF and RVOT dysfunction guided by the discussed hemodynamic assessment, however, more importantly this review should lay the framework for future investigations regarding hemodynamic assessment of this population.

Int J Cardiol: 20 Jul 2016; 221:916-925
Tretter JT, Friedberg MK, Wald RM, McElhinney DB
Int J Cardiol: 20 Jul 2016; 221:916-925 | PMID: 27441469
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Abstract

Prognostic value of induction of atrial fibrillation before and after pulmonary vein isolation.

Adlbrecht C, Gwechenberger M, Richter B, Sipötz J, Kaider A, Gössinger H
Background: Apart from pulmonary vein isolation, catheter ablation of atrial fibrillation (AF) lacks reliable electrophysiological endpoints. The present study investigated the prognostic value of changes in AF inducibility due to ablation. Methods: Between 10/2006 and 10/2009 121 patients referred for catheter ablation of symptomatic, drug refractory paroxysmal AF were included. Sinus rhythm immediately before ablation was a prerequisite for study entry. Two respective attempts to induce AF (>1min) by decremental coronary sinus stimulation before and after ablation were performed. Results: A total of 121 patients aged 59.5±10.4years undergoing pulmonary vein isolation due to paroxysmal AF were included. The median follow-up duration was 12.1months [quartiles: 6.5-20.3months]. In 36 (30%) patients AF was inducible before, but not after ablation. Forty-nine (41%) patients were neither inducible before nor after the procedure, whereas 25 patients (21%) displayed unchanged inducibility. In 11 patients (9%) AF was inducible only after ablation. Patients with inducibility solely after the ablation had the highest risk of AF recurrence (HR 6.71 [95%-CI 2.76-16.30], p=0.0005) compared to patients without inducibility before and after the procedure. Conclusion: The results of attempted AF induction before and after ablation have significance with respect to ablation outcome. Both patient groups with either unchanged inducibility or facilitated induction after ablation had the highest recurrence rates of AF.

Int J Cardiol: 01 Aug 2011; epub ahead of print
Adlbrecht C, Gwechenberger M, Richter B, Sipötz J, Kaider A, Gössinger H
Int J Cardiol: 01 Aug 2011; epub ahead of print | PMID: 21802753
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Abstract

Treatment of segmental pulmonary artery hypertension in adults with congenital heart disease.

Schuuring MJ, Bouma BJ, Cordina R, Gatzoulis MA, ... Celermajer D, Mulder BJ
Introduction: Pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) usually has a homogeneous pressure distribution. More rarely, complex CHD patients have segmental PAH. This is often post-surgically. The characteristics of these patients and their responsiveness to specific pulmonary vasodilator therapy have not been described. Methods: Seven adults with segmental PAH complicating CHD were treated at 3 specialized adult CHD centers between January 2006 and December 2010. Clinical characteristics, six minute walking distances (6MWD), laboratory tests and images were obtained from medical records and the responses to Bosentan, an endothelin-1 receptor antagonist, were assessed. Results: All patients (mean age 32 (23-42) years, five females) had a primary diagnosis pulmonary atresia (PA), four with major aortopulmonary collateral arteries (MAPCAs). Four segmental PAH patients had a right pulmonary artery stenosis, two a left pulmonary artery stenosis and one a unilateral MAPCA stenosis. All patients were symptomatic (functional class II or III) and bosentan was started empirically. Bosentan treatment led to a significant improvement in functional class compared to baseline (1.7±0.5 versus 2.4±0.5; p<0.01). Mean 6MWD (available in 6 patients) increased by 62m (22-150m) from 386±135 to 448±133m (p=0.03) after 12months treatment. Most improvement was seen in patients with low baseline 6MWD. Higher baseline exercise heart rate was significantly associated with lesser improvement in 6MWD (r=-0.91 p=0.01). Laboratory results did not change after initiation of bosentan treatment. Conclusion: This small retrospective case series suggested a significant improvement of functional class and exercise capacity after bosentan treatment in patients with segmental PAH. These findings warrant a prospective study of the potential benefit of selective pulmonary vasodilator therapy in these complex patients. Therefore, we call on treating physicians to share similar cases.

Int J Cardiol: 18 Jul 2011; epub ahead of print
Schuuring MJ, Bouma BJ, Cordina R, Gatzoulis MA, ... Celermajer D, Mulder BJ
Int J Cardiol: 18 Jul 2011; epub ahead of print | PMID: 21763017
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