Journal: Int J Cardiol

Sorted by: date / impact
Abstract

In vitro fertilization exacerbates stroke size and neurological disability in wildtype mice.

Bonetti NR, Meister TA, Soria R, Akhmedov A, ... Beer JH, Scherrer U
Background:
and purpose
Assisted reproductive technologies (ART) induce premature vascular aging in human offspring. The related alterations are well-established risk factors for stroke and predictors of adverse stroke outcome. However, given the young age of the human ART population there is no information on the incidence and outcome of cerebrovascular complications in humans. In mice, ART alters the cardiovascular phenotype similarly to humans, thereby offering the possibility to study this problem.
Methods
We investigated the morphological and clinical outcome after ischemia/reperfusion brain injury induced by transient (45 min) middle cerebral artery occlusion in ART and control mice.
Results
We found that stroke volumes were almost 3-fold larger in ART than in control mice (P < 0.001). In line with these morphological differences, neurological performance assessed by the Bederson and RotaRod tests 24 and 48 h after artery occlusion was significantly worse in ART compared with control mice. Plasma levels of TNF-alpha, were also significantly increased in ART vs. control mice after stroke (P < 0.05). As potential underlying mechanisms, we identified increased blood-brain barrier permeability evidenced by increased IgG extravasation associated with decreased tight junctional protein claudin-5 and occludin expression, increased oxidative stress and decreased NO-bioactivity in ART compared with control mice.
Conclusions
In wildtype mice, ART predisposes to significantly worse morphological and functional stroke outcomes, related at least in part to altered blood-brain barrier permeability. These findings demonstrate that ART, by inducing premature vascular aging, not only is a likely risk factor for stroke-occurrence, but also a mediator of adverse stroke-outcome.
Translational perspective
This study highlights that ART not only is a likely risk factor for stroke-occurrence, but also a mediator of adverse stroke-outcome. The findings should raise awareness in the ever-growing human ART population in whom these techniques cause similar alterations of the cardiovascular phenotype and encourage early preventive and diagnostic efforts.

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

Int J Cardiol: 14 Nov 2021; 343:92-101
Bonetti NR, Meister TA, Soria R, Akhmedov A, ... Beer JH, Scherrer U
Int J Cardiol: 14 Nov 2021; 343:92-101 | PMID: 34437933
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Impact:
Abstract

The clinical presentation and outcome of aortic coarctation associated with left ventricular inflow and outflow tract lesion in adult patients: Shone syndrome and beyond.

Khan U, Shaw T, Kempny A, Gatzoulis MA, Dimopoulos K, Li W
Background
Aortic coarctation (AoCoa) is a congenital stenosis of aorta, which often co-exists with other congenital heart defects. Many studies have shown the importance of regular follow-up in these patients however there is scarcity of knowledge relating to the impact of left ventricle inflow lesions (LVIT) and left ventricle outflow track lesions (LVOT). The aim of this study is to evaluate the impact of isolated AoCoa with LVIT and/or LVOT on haemodynamic, morbidity and mortality.
Methods
We have retrospectively analysed clinical data of all adult AoCoa patients who underwent echocardiography between 2010-2018 in our centre. Outcome measures included death, number of hospitalisations for cardiac causes, development of cardiac arrhythmia, new prescription of HF medication.
Results
A total of 406 AoCoa patients were included and were followed for a median 4.2 years. At baseline, 38% patients had AoCoa alone, 54% patients had LVOT, 3% patients had LVIT, and 5% patients had mixed LVIT and LVOT, including patients with Shone syndrome. Patients with mixed LVIT and LVOT had the highest mortality of the four groups and the highest heart failure-related morbidity. Moreover, they were the most prone to have a higher indexed LA volume compared to patients with no LVOT (p=0.0001). During follow-up, 13 patients died, of which 21% patients were from the mixed LVIT and LVOT group.
Conclusions
AoCoa patients with a combination of LVIT and LVOT including Shone complex are associated with a significantly higher morbidity and mortality compared to AoCoa alone.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 Nov 2021; 343:45-49
Khan U, Shaw T, Kempny A, Gatzoulis MA, Dimopoulos K, Li W
Int J Cardiol: 14 Nov 2021; 343:45-49 | PMID: 34453975
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Abstract

Ventricular assist devices in paediatric cardiomyopathy and congenital heart disease: An analysis of the German National Register for Congenital Heart Defects.

Lammers AE, Sprenger KS, Diller GP, Miera O, ... Tutarel O, German Competence Network for Congenital Heart Defects Investigators
Background
Ventricular assist devices (VAD) are increasingly used in patients with end-stage heart failure due to acquired heart disease. Limited data exists on the use and outcome of this technology in children.
Methods
All children (<18 years of age) with VAD support included in the German National Register for Congenital Heart Defects were identified and data on demographics, underlying cardiac defect, previous surgery, associated conditions, type of procedure, complications and outcome were collected.
Results
Overall, 64 patients (median age 2.1 years; 45.3% female) receiving a VAD between 1999 and 2015 at 8 German centres were included in the analysis. The underlying diagnosis was congenital heart disease (CHD) in 25 and cardiomyopathy in 39 children. The number of reported VAD implantations increased from 13 in the time period 2000-2004 to 27 implantations in the time period 2010-2014. During a median duration of VAD support of 54 days, 28.1% of patients experienced bleeding complications (6.3% intracerebral bleeding), 14.1% thrombotic (10.9% VAD thrombosis) and 23.4% thromboembolic complications (including cerebral infarction in 18.8% of patients). Children with cardiomyopathy were more likely to receive a cardiac transplantation (79.5% vs. 28.0%) compared to CHD patients. Survival of cardiomyopathy patients was significantly better compared to the CHD cohort (p < 0.0001). Multivariate Cox-proportional analysis revealed a diagnosis of CHD (hazard ratio [HR] 4.04, p = 0.001), age at VAD implantation (HR 1.09/year, p = 0.04) and the need for pre-VAD extracorporeal membrane oxygenation (ECMO) support (HR 3.23, p = 0.03) as independent predictors of mortality.
Conclusions
The uptake of VAD therapy in children is increasing. Morbidity and mortality remain high, especially in patients with congenital heart disease and those requiring ECMO before VAD implantation.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 Nov 2021; 343:37-44
Lammers AE, Sprenger KS, Diller GP, Miera O, ... Tutarel O, German Competence Network for Congenital Heart Defects Investigators
Int J Cardiol: 14 Nov 2021; 343:37-44 | PMID: 34487787
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Impact:
Abstract

Comparative effectiveness of endovascular treatment modalities for de novo femoropopliteal lesions in intermittent claudication: A network meta-analysis of randomized controlled trials.

Zhou Y, Wang J, He H, Li Q, ... Li X, Shu C
Purpose
To evaluate the most effective endovascular treatment modalities for de novo femoropopliteal lesions in intermittent claudication (IC) in terms of technical success, primary patency, target lesion revascularization (TLR) and all-cause mortality through network meta-analysis of randomized controlled trials.
Methods
Medical databases were searched on December 3, 2020. 16 studies (3265 patients) and 7 treatments were selected. Outcomes were technical success, primary patency, TLR and mortality at 6 and/or 12 months.
Results
Regarding 6-month primary patency, drug-eluting stents (DES) was better than balloon angioplasty (BA; odds ratio [OR], 23.27; 95% confidence interval [CI], 12.57-43.06), drug-coated balloons (DCB; OR, 5.63; 95% CI, 2.26-14.03) and directional atherectomy (DA; OR, 31.52; 95% CI, 7.81-127.28), and bare nitinol stents (BNS) was better than BA (OR, 17.91; 95% CI, 7.22-44.48), DCB (OR, 4.33; 95% CI, 1.40-13.45) and DA (OR, 24.27; 95% CI, 5.16-114.11). Regarding 12-month primary patency, DES was better than BA (OR, 10.05; 95% CI, 4.56-22.16), DCB (OR, 3.70; 95% CI, 1.54-8.89) and DA (OR, 29.54; 95% CI, 7.26-120.26). DCB and combination of balloon and atherectomy were the most effective treatment regarding 12-month TLR and technical success (residual stenosis <30%), respectively. DES, BNS and DA with DCB (DA-DCB) were included in the best cluster in the clustered ranking plot combining 12-month primary patency and TLR.
Conclusions
Balloon and atherectomy may confer advantages over other treatments for technical success; DCB may for TLR. Stent technologies confer substantial advantages regarding primary patency. Stent technologies and DA-DCB should be given priority in treating femoropopliteal lesions in IC.

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

Int J Cardiol: 14 Nov 2021; 343:122-130
Zhou Y, Wang J, He H, Li Q, ... Li X, Shu C
Int J Cardiol: 14 Nov 2021; 343:122-130 | PMID: 34461162
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Abstract

Cardiovascular magnetic resonance characterisation of anthracycline cardiotoxicity in adults with normal left ventricular ejection fraction.

Harries I, Berlot B, Ffrench-Constant N, Williams M, ... Plana JC, Bucciarelli-Ducci C
Background
Anthracycline therapy may lead to changes in cardiac structure and function not detectable by solely evaluating left ventricular ejection fraction (LVEF).
Objectives
We hypothesized that cardiovascular magnetic resonance (CMR) would identify structural and functional myocardial abnormalities in anthracycline-treated cancer survivors with normal LVEF, compared to a matched control population.
Methods
Forty-five cancer survivors (56 ± 16 yrs., 60% female) with normal LVEF (59.5 ± 4.1%) were studied a median of 11 months (range 3-36) following administration of 237 ± 83 mg/m2 anthracycline, and compared with forty-five healthy control subjects of similar age and sex (53 ± 16 yrs., 60% female) with normal LVEF (60.8 ± 2.4%) using 1.5 T CMR.
Results
Significantly smaller indexed left ventricular mass (45.6 ± 8.7 vs 50.3 ± 10.1 g/m2, p = 0.02) and indexed myocardial cell volume (30.5 ± 5.7 vs 34.8 ± 7.2 ml/m2, p = 0.002) were evident in cancer survivors and the latter was inversely associated with cumulative anthracycline dose (r = -0.31, p = 0.02). Surrogate CMR markers of myocardial fibrosis were significantly increased in cancer survivors (native myocardial T1: 1021 ± 40 vs 996 ± 35 ms, p = 0.002; extracellular volume: 29.5 ± 4.5 vs 27.4 ± 2.3%, p = 0.006). CMR-derived feature-tracking global longitudinal strain (GLS) was significantly impaired in cancer survivors (2D GLS -18.3 ± 2.6 vs -20.0 ± 2.0%, p < 0.001; 3D GLS -14.5 ± 2.3 vs -16.4 ± 2.6%, p < 0.001). Parameters exhibited good to excellent (ICC = 0.86-0.98) inter- and intra-observer reproducibility.
Conclusions
Anthracycline-treated cancer survivors with normal LVEF have significant perturbations of LV mass, myocardial cell volume, native myocardial T1, ECV, CMR-derived 2D and 3D GLS, compared to controls, with good to excellent levels of inter- and intra-observer reproducibility.

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

Int J Cardiol: 14 Nov 2021; 343:180-186
Harries I, Berlot B, Ffrench-Constant N, Williams M, ... Plana JC, Bucciarelli-Ducci C
Int J Cardiol: 14 Nov 2021; 343:180-186 | PMID: 34454967
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Abstract

Impact of vascular morphology and plaque characteristics on computed tomography derived fractional flow reserve in early stage coronary artery disease.

Tsugu T, Tanaka K, Belsack D, Devos H, ... De Maeseneer M, De Mey J
Background
Computed-tomography (CT) derived fractional-flow-reserve (FFRCT) gradually may decrease from proximal to distal vessels even without apparent coronary artery disease (CAD). It may be unclear whether the decrease in FFRCT at the distal coronal artery is physiological or due to stenosis. We decided to study predictive factors of an FFRCT decline below the pathological value of 0.80 in no-apparent CAD.
Methods
A total of 150 consecutive patients who had both CT angiography coupled to FFRCT analysis and invasive angiogram showing < 20% coronary stenosis were included. Vessels were divided into two groups according to FFRCT at the distal vessel: FFRCT > 0.80 (n = 317) and FFRCT ≤ 0.80 (n = 114). ΔFFRCT was defined as the change in FFRCT from proximal to distal vessel. Vessel morphology (vessel length and lumen volume) and plaque characteristics [low-attenuation plaque volume, intermediate-attenuation (IAP) plaque volume, and calcified plaque volume] were evaluated.
Results
FFRCT decreased from proximal to distal for the three major vessels in both FFRCT > 0.80 and FFRCT ≤ 0.80. Compared to FFRCT > 0.80, IAP volume was significantly higher in all three major vessels in FFRCT ≤ 0.80. ΔFFRCT was correlated with vessel length and lumen volume in FFRCT > 0.80, whereas ΔFFRCT was correlated with IAP volume in FFRCT ≤ 0.80. IAP volume above 44.8 mm3 was the strongest predictor of distal FFRCT of ≤ 0.80.
Conclusions
The presence of IAP is a major predictor of gradual decrease of FFRCT below 0.80 in no-apparent CAD vessels. Vessel morphology and plaque characteristics should be considered when interpreting FFRCT.

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

Int J Cardiol: 14 Nov 2021; 343:187-193
Tsugu T, Tanaka K, Belsack D, Devos H, ... De Maeseneer M, De Mey J
Int J Cardiol: 14 Nov 2021; 343:187-193 | PMID: 34454964
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Impact:
Abstract

Psoriasis and its impact on the clinical outcome of patients with pulmonary embolism.

Keller K, Hobohm L, Ostad MA, Karbach S, ... Steinbrink K, Gori T
Background
An increased risk for venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep venous thrombosis, has been reported in psoriasis patients. The impact of psoriasis on prognosis of VTE patients is widely unknown.
Methods
Hospitalized PE patients were stratified for psoriasis and the impact of psoriasis on outcome was investigated in the German nationwide inpatient sample of the years 2005-2017.
Results
Overall, 1,076,384 hospitalizations of PE patients (53.7% females, median age 72.0 [60.0-80.0] years) were recorded in Germany 2005-2017. Among these, 3145 patients had psoriasis (0.3%). Psoriatic PE patients were younger (68.0 [57.0-76.0] vs. 72.0 [60.0-80.0] years,P < 0.001) and more often male (64.1% vs. 46.3%,P < 0.001). The prevalence of VTE risk factors, traditional cardiovascular risk factors and cardiovascular comorbidities was higher in psoriatic than in non-psoriatic individuals. Psoriatic PE patients showed a lower in-hospital case-fatality rate (11.1% vs. 16.0%,P < 0.001), confirmed by logistic regressions showing an independent association of psoriasis with reduced case-fatality rate (OR 0.73 [95%CI 0.65-0.82],P < 0.001), despite higher prevalence of pneumonia (24.8% vs. 23.2%,P = 0.029). Psoriasis was an independent predictor for gastro-intestinal bleeding (OR 1.35 [95%CI 1.04-1.75],P = 0.023) and transfusion of blood constituents (OR 1.23 [95%CI 1.11-1.36],P < 0.001).
Conclusions
PE patients with psoriasis were hospitalized in median four years earlier than those without. Although psoriasis was associated with an unfavorable cardiovascular-risk and VTE-risk profile in PE patients, our data demonstrate a lower in-hospital mortality in psoriatic PE, which might be mainly driven by younger age. Our findings may improve the clinical management of these patients and contribute evidence for relevant systemic manifestation of psoriasis.
Translational perspective
An increased risk for venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep venous thrombosis, has been reported in psoriasis patients, but the impact of psoriasis on prognosis of VTE patients is widely unknown. PE patients with psoriasis were younger and psoriasis was associated with an unfavorable cardiovascular-risk and VTE-risk profile. In-hospital mortality was lower in psoriatic PE patients, which might be mainly driven by younger age. Our findings improve the clinical management of PE patients and contribute evidence for relevant systemic manifestation of psoriasis.
One sentence summary
Psoriasis with chronic inflammation promotes PE development, is associated with an unfavorable cardiovascular and VTE-risk profile, but lower in-hospital mortality.

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

Int J Cardiol: 14 Nov 2021; 343:114-121
Keller K, Hobohm L, Ostad MA, Karbach S, ... Steinbrink K, Gori T
Int J Cardiol: 14 Nov 2021; 343:114-121 | PMID: 34480990
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Impact:
Abstract

Coronary plaque and clinical characteristics of South Asian (Indian) patients with acute coronary syndromes: An optical coherence tomography study.

Nakajima A, Subban V, Russo M, Bryniarski KL, ... Sankardas MA, Jang IK
Background
South Asians, and Indians in particular, are known to have a higher incidence of premature atherosclerosis and acute coronary syndromes (ACS) with worse clinical outcomes, compared to populations with different ethnic backgrounds. However, the underlying pathobiology accounting for these differences has not been fully elucidated.
Methods
ACS patients who had culprit lesion optical coherence tomography (OCT) imaging were enrolled. Culprit plaque characteristics were evaluated using OCT.
Results
Among 1315 patients, 100 were South Asian, 1009 were East Asian, and 206 were White. South Asian patients were younger (South Asians vs. East Asians vs. Whites: 51.6 ± 13.4 vs. 65.4 ± 11.9 vs. 62.7 ± 11.7; p < 0.001) and more frequently presented with ST-segment elevation myocardial infarction (STEMI) (77.0% vs. 56.4% vs. 35.4%; p < 0.001). On OCT analysis after propensity group matching, plaque erosion was more frequent (57.0% vs. 38.0% vs. 50.0%; p = 0.003), the lipid index was significantly greater (2281.6 [1570.8-3160.6] vs. 1624.3 [940.9-2352.4] vs. 1303.8 [1090.0-1757.7]; p < 0.001), and the prevalence of layered plaque was significantly higher in the South Asian group than in the other two groups (52.0% vs. 30.0% vs. 34.0%; p = 0.003).
Conclusions
Compared to East Asians and Whites, South Asians with ACS were younger and more frequently presented with STEMI. Plaque erosion was the predominant pathology for ACS in South Asians and their culprit lesions had more features of plaque vulnerability.
Clinical trial registration
http://www.clinicaltrials.gov, NCT03479723.

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

Int J Cardiol: 14 Nov 2021; 343:171-179
Nakajima A, Subban V, Russo M, Bryniarski KL, ... Sankardas MA, Jang IK
Int J Cardiol: 14 Nov 2021; 343:171-179 | PMID: 34487786
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Impact:
Abstract

Assessment of independent clinical predictors of early readmission after percutaneous endoluminal left atrial appendage closure with the Watchman device using National Readmission Database.

Rahman MU, Amritphale A, Kumar S, Trice C, Awan GM, Omar BA
Background
Percutaneous endoluminal left atrial appendage closure (pLAAC) procedure has been used to prevent strokes in patients who are not eligible for long-term prophylactic anticoagulation. Since its approval, multiple studies have looked at its efficacy with comparable outcomes to anticoagulation, the current standard of care.
Objectives
To assess the readmission rate and determine the factors associated with readmission after the endocardial pLAAC procedure using the Watchman device.
Methods
Data was obtained from the National Readmission Database (NRD), and we used SPSS software to determine statistically significant clinical predictors affecting readmission after implantation of the Watchman device at 30 days.
Results
The rate of readmission was found to be 9.2%. The true median cost of index hospitalization for the total population in the study was found to be [median (interquartile range = IQR), p] USD 24594 (USD 18883-31,041), whereas the true median cost of admission for those who were getting readmitted after 30 days was [median (IQR)] USD 7699 (USD 4955-14,243). Multivariate analysis of all clinically relevant predictors showed adjusted ratio for [adjusted odds ratio (OR), 95% confidence interval (95% CI), p-value] female genders (1.288, 1.104-1.503, p = 0.001), discharge to home health care (6.155, 1.509-25.096, p = 0.01), chronic kidney disease (CKD) (1.847,1.511-2.258, p < 0.001), chronic lung disease (1.419, 1.194-1.686, p < 0.001), heart failure (1.280, 1.040-1.574, p = 0.02), pericardial disorders (1.485, 1.011-2.179, p = 0.04), fluid and electrolyte disorders (1.456,1.050-2.018, p = 0.02) in those who were getting readmitted at 30-days compared to those who were not readmitted. The median length of stay for the index hospitalization was found to be one day, whereas the median length of stay at the 30-day readmission was reported to be [Median (IQR)] 4 days (2-6 days). Major cardiac reasons for readmission were heart failure, arrhythmias, and pericardial disorders.
Conclusion
Our study aims to assess 30-day outcomes in the US population after pLAAC using a Watchman device. Our analysis showed that one in ten patients were getting readmitted. In addition, chronic kidney disease, chronic obstructive pulmonary disease, heart failure, and pericardial disorders were associated with higher readmission rates. These findings will help us assess clinical correlations and predict which patients are more at risk of readmission after a Watchman procedure.

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

Int J Cardiol: 14 Nov 2021; 343:21-26
Rahman MU, Amritphale A, Kumar S, Trice C, Awan GM, Omar BA
Int J Cardiol: 14 Nov 2021; 343:21-26 | PMID: 34481838
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Impact:
Abstract

Coronary artery spasm and impaired myocardial perfusion in patients with ANOCA: Predictors from a multimodality study using stress CMR and acetylcholine testing.

Pirozzolo G, Martínez Pereyra V, Hubert A, Guenther F, ... Ong P, Seitz A
Background
Functional coronary disorders such as coronary spasm and microvascular dysfunction (including microvascular spasm and impaired microvascular dilatation) are frequent findings among patients with angina and non-obstructed coronary arteries (ANOCA). In this study, we investigated a potential association of coronary spasm and myocardial perfusion abnormalities as well as predictors of such functional coronary disorders in ANOCA patients using a multimodality diagnostic strategy including adenosine stress CMR and intracoronary acetylcholine testing.
Methods
We enrolled 129 patients with ANOCA who underwent acetylcholine testing and adenosine stress perfusion CMR. Patients were allocated to 3 groups according to their spasm testing result with regard to standardized COVADIS criteria: 1) epicardial spasm, 2) microvascular spasm, and 3) no spasm. The myocardial perfusion reserve index (MPRI) was semiquantitatively determined from adenosine stress perfusion CMR. Multivariate regression analyses were performed to identify predictors of coronary functional disorders.
Results
Patients with epicardial spasm had lower MPRI than patients without, whereas MPRI was preserved in patients with microvascular spasm. Multivariate analyses revealed age, previous myocardial infarction, LVEF and epicardial spasm as independent predictors of diminished MPRI, whereas previous PCI was associated with epicardial spasm, and female sex was a strong predictor of microvascular spasm.
Conclusions
Our results demonstrate coexistence of different functional coronary disorder endotypes involving the macro- and microvascular level of the coronary circulation in patients with ANOCA. We demonstrate that epicardial spasm is associated with diminished myocardial perfusion reserve and report further predictors of coronary functional disorders.

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

Int J Cardiol: 14 Nov 2021; 343:5-11
Pirozzolo G, Martínez Pereyra V, Hubert A, Guenther F, ... Ong P, Seitz A
Int J Cardiol: 14 Nov 2021; 343:5-11 | PMID: 34499976
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Impact:
Abstract

Severity of pulmonary embolism at initial diagnosis and long-term clinical outcomes: From the COMMAND VTE Registry.

Yamashita Y, Morimoto T, Kadota K, Takase T, ... Kimura T, COMMAND VTE Registry Investigators
Background
There is a paucity of data on the long-term clinical outcomes according to the severity of pulmonary embolism (PE) at initial diagnosis.
Methods
The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic venous thromboembolism (VTE). After excluding 1312 patients without PE, the current study population consisted of 1715 patients with PE, who were divided into 3 groups according to the clinical severity; massive PE, sub-massive PE and low-risk PE.
Results
There were 179 patients (10%) with massive PE, 742 patients (43%) with sub-massive PE, and 794 patients (46%) with low-risk PE. By the landmark analysis at 3 months, the cumulative incidences of recurrent VTE were similar among the 3 groups both within and beyond 3 months (Massive PE: 2.9%, Sub-massive PE: 4.2%, and Low-risk PE: 3.3%, P = 0.61, and 4.3%, 8.8%, and 7.8% at 5 years, P = 0.47, respectively). After adjusting confounders, the risk of massive PE relative to low-risk PE for recurrent VTE beyond 3 months remained insignificant (adjusted HR 0.54, 95% CI: 0.13-1.51, P = 0.27). Patients with massive PE at initial diagnosis more often presented as severe recurrent PE events than those with sub-massive and low-risk PE.
Conclusions
In the current real-world large registry, the long-term risk of overall recurrent VTE in patients with massive PE at initial diagnosis did not significantly differ from those with sub-massive and low-risk PE beyond 3 months, although patients with massive PE at initial diagnosis more frequently developed recurrent VTE as PE with severe clinical presentation.

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

Int J Cardiol: 14 Nov 2021; 343:107-113
Yamashita Y, Morimoto T, Kadota K, Takase T, ... Kimura T, COMMAND VTE Registry Investigators
Int J Cardiol: 14 Nov 2021; 343:107-113 | PMID: 34499975
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Abstract

The impact of peripheral artery disease on major adverse cardiovascular events following myocardial infarction.

Andersen P, Kragholm K, Torp-Pedersen C, Jensen SE, Attar R
Aims
Peripheral artery disease (PAD) constitute a high-risk with adverse clinical outcomes. We aimed to investigate the cardiovascular outcomes following myocardial infarction (MI).
Methods and results
This nationwide, Danish register-based follow-up study includes all patients experiencing an MI between 2000 and 2017. Patients with and without PAD were compared. Multivariable logistic regression was used to derive relative risks of 1-year major adverse cardiovascular events (MACE; all-cause mortality, reinfarction, stroke or heart failure). Individual components, cardiovascular mortality, and bleeding, standardized to age, sex and comorbidity distributions of all patients were assessed. MI patients with PAD (n = 5083, 2.9%) were older and more comorbid compared to patients without PAD (n = 174,673). After standardization, PAD was associated with higher 1-year relative risks of MACE (RR 1.21 [95% CI 1.17;1.25]), all-cause (RR 1.29 [95% CI 1.24;1.35]) and cardiovascular mortality (RR 1.3 [95% CI 1.24;1.36]), reinfarction (RR 1.17 [95% CI 1.11;1.22]), stroke (RR 1.12 [95% CI 0.92;1.32]), heart failure (RR 1.22 [95% CI 1.12;1.32]), and bleeding episodes (RR 1.25 [95% CI 1.04,1.46]). Similar results were seen in 30-day survivors after adjustment for antithrombotic post-discharge medication for MACE (RR 1.25 [95% CI 1.20,1.31]), all-cause mortality (RR 1.47 [95% CI 1.37,1.57], cardiovascular mortality (RR 1.49 [95% CI 1.37,1.61]), reinfarction (RR 1.17 [95% CI 1.08,1.12]) and heart failure (RR 1.22 [95% CI 1.12,1.32]).
Conclusion
Comparing to patients without PAD, patients with PAD had increased 1-year relative risk of MACE, all-cause mortality, reinfarction, stroke, heart failure, cardiovascular mortality and bleeding following MI. The low prevalence of PAD is suggestive of considerable under-diagnosing.

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

Int J Cardiol: 14 Nov 2021; 343:131-137
Andersen P, Kragholm K, Torp-Pedersen C, Jensen SE, Attar R
Int J Cardiol: 14 Nov 2021; 343:131-137 | PMID: 34499974
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Impact:
Abstract

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients.

Al-Rubaish AM, Al-Muhanna FA, Alshehri AM, Al-Mansori MA, ... Asselbergs FW, Al-Ali AK
Background
ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor.
Methods
This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI.
Results
STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20-0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11-0.53), cardiovascular death (OR 0.16, 95%CI0.06-0.42) and major bleeding (OR 0.49, 95%CI 0.32-0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43-1.71).
Conclusion
A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy.

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

Int J Cardiol: 14 Nov 2021; 343:15-20
Al-Rubaish AM, Al-Muhanna FA, Alshehri AM, Al-Mansori MA, ... Asselbergs FW, Al-Ali AK
Int J Cardiol: 14 Nov 2021; 343:15-20 | PMID: 34506827
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Impact:
Abstract

Cancer and cardiovascular disease: The impact of cardiac rehabilitation and cardiorespiratory fitness on survival.

Williamson T, Moran C, Chirico D, Arena R, ... Campbell T, Laddu D
Background
Cancer survivors are at increased risk for cardiovascular disease (CVD)-related morbidity and mortality. Exercise-based cardiac rehabilitation (CR) programs improve CVD risk factors, including cardiorespiratory fitness (CRF). The purpose of this study was to investigate: (1) the association between CR completion and survival, and (2) whether CRF improvements translate to increased survival among patients with comorbid cancer and CVD.
Methods
Patients with CVD and pre-existing cancer (any type) were referred to a 12-week exercise-based CR program between 01/1996 and 03/2016. Peak metabolic equivalents (METs) were assessed by graded exercise test pre-CR and at 12-weeks. Kaplan-Meier survival and multivariate cox regressions were performed to evaluate impact of CR completion and clinically-meaningful CRF improvements [ΔMETs≥1] on survival, adjusting for relevant covariates.
Results
Among 442 patients with CVD and cancer referred to CR (67 ± 10 years; 22% women), 361 (82%) completed CR. 102 deaths were recorded during the 12-year observation period. Compared to patients who did not complete CR, patients with comorbid cancer who completed CR demonstrated a survival advantage (63% vs 80.1%, p < .001). CRF improved among completers during the 12-week program (mean change = 0.87 ± 0.93 METs, p < .001); 41% experienced a clinically-meaningful ΔMETs≥1. A survival advantage was not observed in completers who experienced a ΔMETs≥1 improvement (p = .254).
Conclusion
Completing a 12-week exercise-based CR program improved CRF and increased survival in patients with CVD and comorbid cancer. The results highlight the survival benefits of completing a CR program among CVD patients who experience added barriers imposed by cancer treatment and survival.

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

Int J Cardiol: 14 Nov 2021; 343:139-145
Williamson T, Moran C, Chirico D, Arena R, ... Campbell T, Laddu D
Int J Cardiol: 14 Nov 2021; 343:139-145 | PMID: 34506825
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Impact:
Abstract

Platelet reactivity is higher in e-cigarette vaping as compared to traditional smoking.

Metzen D, M\'Pembele R, Zako S, Mourikis P, ... Dannenberg L, Polzin A
Introduction
Vaping emerges as alternative to standard tobacco smoking. However, there is evidence for critical cardiovascular, gastrointestinal and respiratory side effects. Nevertheless, long-term vaping effects on thrombocyte reactivity have not been investigated. Therefore, we investigated the influence of vaping on thrombocyte reactivity in comparison to standard smoking and non-smoking.
Methods
Platelet function was measured by Multiplate Impedance Aggregometry as area under the curve (AUC). Smoking habits and characteristics were assessed by questionnaire. Results were analyzed using inverse probability of treatment weighting (IPTW) and conventional t-tests to test for robustness.
Results
After IPTW adjustment, participants in all groups were balanced by age, gender, body height and weight. Collagen-induced aggregation was higher in vapers compared to non-smokers (non-smokers 52.55 ± 23.97 vs. vapers 66.63 ± 18.96 AUC, p = 0.002) and to smokers (vapers vs. smokers 49.50 ± 26.05 AUC, p < 0.0001). ADP-induced aggregation in vapers was higher compared to non-smokers (non-smokers 33.16 ± 16.61 vs. vapers 45.27 ± 18.67 AUC, p = 0.001) and was numerically increased compared to smokers (vapers vs. smokers 40.09 ± 19.80 AUC, p = 0.08). These findings remained robust in t-test analysis.
Conclusion
This study provides first evidence that vaping leads to enhanced platelet reactivity compared to standard smoking and non-smoking. This suggests health effects of vaping might be more severe than previously assumed. Whether this effect translates to clinical outcome with a higher incidence of major cardiovascular events, should be evaluated in large-scaled clinical studies.

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

Int J Cardiol: 14 Nov 2021; 343:146-148
Metzen D, M'Pembele R, Zako S, Mourikis P, ... Dannenberg L, Polzin A
Int J Cardiol: 14 Nov 2021; 343:146-148 | PMID: 34506824
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Impact:
Abstract

Effects of the exercise training on skeletal muscle oxygen consumption in heart failure patients with reduced ejection fraction.

Guimarães GV, Ribeiro F, Castro RE, Roque JM, ... Ferreira SA, Bocchi EA
Aims
Skeletal muscle dysfunction is a systemic consequence of heart failure (HF) that correlates with functional capacity. However, the impairment within the skeletal muscle is not well established. We investigated the effect of exercise training on peripheral muscular performance and oxygenation in HF patients.
Methods and results
HF patients with ejection fraction ≤40% were randomized 2:1 to exercise training or control for 12 weeks. Muscle tissue oxygen was measured noninvasively by near-infrared spectroscopy (NIRS) during rest and a symptom-limited cardiopulmonary exercise test (CPET) before and after intervention. Measurements included skeletal muscle oxygenated hemoglobin concentration, deoxygenated hemoglobin concentration, total hemoglobin concentration, VO2 peak, VE/VCO2 slope, and heart rate. Muscle sympathetic nerve activity by microneurography, and muscle blood flow by plethysmography were also assessed at rest pre and post 12 weeks. Twenty-four participants (47.5 ± 7.4 years, 58% men, 75% no ischemic) were allocated to exercise training (ET, n = 16) or control (CG, n = 8). At baseline, no differences between groups were found. Exercise improved VO2 peak, slope VE/VCO2, and heart rate. After the intervention, significant improvements at rest were seen in the ET group in muscle sympathetic nerve activity and muscle blood flow. Concomitantly, a significant decreased in Oxy-Hb (from 29.4 ± 20.4 to 15.7 ± 9.0 μmol, p = 0.01), Deoxi-Hb (from 16.3 ± 8.2 to 12.2 ± 6.0 μmol, p = 0.003) and HbT (from 45.7 ± 27.6 to 27.7 ± 13.4 μmol, p = 0.008) was detected at peak exercise after training. No changes were observed in the control group.
Conclusion
Exercise training improves skeletal muscle function and functional capacity in HF patients with reduced ejection fraction. This improvement was associated with increased oxygenation of the peripheral muscles, increased muscle blood flow, and decreased sympathetic nerve activity.

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

Int J Cardiol: 14 Nov 2021; 343:73-79
Guimarães GV, Ribeiro F, Castro RE, Roque JM, ... Ferreira SA, Bocchi EA
Int J Cardiol: 14 Nov 2021; 343:73-79 | PMID: 34506822
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Impact:
Abstract

Feasibility of late gadolinium enhancement (LGE) in ischemic cardiomyopathy using 2D-multisegment LGE combined with artificial intelligence reconstruction deep learning noise reduction algorithm.

Muscogiuri G, Martini C, Gatti M, Dell\'Aversana S, ... Pepi M, Pontone G
Background
Despite the low spatial resolution of 2D-multisegment late gadolinium enhancement (2D-MSLGE) sequences, it may be useful in uncooperative patients instead of standard 2D single segmented inversion recovery gradient echo late gadolinium enhancement sequences (2D-SSLGE). The aim of the study is to assess the feasibility and comparison of 2D-MSLGE reconstructed with artificial intelligence reconstruction deep learning noise reduction (NR) algorithm compared to standard 2D-SSLGE in consecutive patients with ischemic cardiomyopathy (ICM).
Methods
Fifty-seven patients with known ICM referred for a clinically indicated CMR were enrolled in this study. 2D-MSLGE were reconstructed using a growing level of NR (0%,25%,50%,75%and 100%). Subjective image quality, signal to noise ratio (SNR) and contrast to noise ratio (CNR) were evaluated in each dataset and compared to standard 2D-SSLGE. Moreover, diagnostic accuracy, LGE mass and scan time were compared between 2D-MSLGE with NR and 2D-SSLGE.
Results
The application of NR reconstruction ≥50% to 2D-MSLGE provided better subjective image quality, CNR and SNR compared to 2D-SSLGE (p < 0.01). The best compromise in terms of subjective and objective image quality was observed for values of 2D-MSLGE 75%, while no differences were found in terms of LGE quantification between 2D-MSLGE versus 2D-SSLGE, regardless the NR applied. The sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 2D-MSLGE NR 75% were 87.77%,96.27%,96.13%,88.16% and 94.22%, respectively. Time of acquisition of 2D-MSLGE was significantly shorter compared to 2D-SSLGE (p < 0.01).
Conclusion
When compared to standard 2D-SSLGE, the application of NR reconstruction to 2D-MSLGE provides superior image quality with similar diagnostic accuracy.

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

Int J Cardiol: 14 Nov 2021; 343:164-170
Muscogiuri G, Martini C, Gatti M, Dell'Aversana S, ... Pepi M, Pontone G
Int J Cardiol: 14 Nov 2021; 343:164-170 | PMID: 34517017
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Impact:
Abstract

Non-cardiology vs. cardiology care of patients with heart failure and reduced ejection fraction is associated with lower use of guideline-based care and higher mortality: Observations from The Swedish Heart Failure Registry.

Kapelios CJ, Canepa M, Benson L, Hage C, ... Savarese G, Lund LH
Background
Patients with heart failure (HF) are often cared for by non-cardiologists. The implications are unknown.
Methods
In a nationwide HF cohort with reduced ejection fraction (HFrEF), we compared demographics, clinical characteristics, guideline-based therapy use and outcomes in non-cardiology vs. cardiology in-patient and out-patient care.
Results
Between 2000 and 2016, 36,076 patients with HFrEF were enrolled in the Swedish HF registry (19,337 [54%] in-patients overall), with 44% of in-patients and 45% of out-patients managed in non-cardiology settings. Predictors of treatment in non-cardiology were age > 75 years (adjusted odds ratio for non-cardiology 1.20; 95% confidence interval 1.14-1.27), lower education level (0.71; 0.66-0.76 for university vs. compulsory), valve disease (1.24; 1.18-1.31) and systolic blood pressure (SBP) >120 mmHg (1.05; 1.00-1.10). Non-cardiology care was significantly associated with lower use of beta-blockers (0.80; 0.74-0.86) and devices (intracardiac defibrillator [ICD] and/or cardiac resynchronization therapy [CRT]: 0.63; 0.56-0.71), and less frequent specialist follow-up (0.61; 0.57-0.65). Over 1-year follow-up the risk of all-cause mortality (adjusted hazard ratio 1.09; 1.03-1.15) was higher but the risk of first HF (re-) hospitalization was lower (0.93; 0.89-0.97) in non-cardiology vs. cardiology care.
Conclusions
In HFrEF, non-cardiology care was independently associated with older ageand lower education. After covariate adjustment, non-cardiology care was associated with lower use of beta-blockers and devices, higher mortality, and lower risk of HF hospitalization. Access to cardiology care may not be equitable and this may have implications for use of guideline-based care and outcomes.

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

Int J Cardiol: 14 Nov 2021; 343:63-72
Kapelios CJ, Canepa M, Benson L, Hage C, ... Savarese G, Lund LH
Int J Cardiol: 14 Nov 2021; 343:63-72 | PMID: 34517016
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Impact:
Abstract

Sex differences in incidence of out-of-hospital cardiac arrest across ethnic and socioeconomic groups: A population-based cohort study in the Netherlands.

Bolijn R, Sieben CHAM, Kunst AE, Blom M, Tan HL, van Valkengoed IGM
Background
Insight into the occurrence of out-of-hospital cardiac arrest (OHCA) within general populations may help to target prevention strategies. Case registries suggest that there may be substantial differences in emergency medical service (EMS)-attended OHCA incidence between men and women, but relative sex differences across ethnic groups and socioeconomic (SES) groups have not been studied. We investigated sex differences in OHCA incidence, overall and across these subgroups.
Methods
We performed a retrospective population-based cohort study, combining individual-level data on ethnicity and income (as SES measure) from Statistics Netherlands of all men and women aged ≥25 years living in one study region in the Netherlands on 01-01-2009 (n = 1,688,285) with prospectively collected EMS-attended OHCA cases (n = 5676) from the ARREST registry until 31-12-2015. We calculated age-standardised incidence rates of OHCA. Sex differences were assessed with Cox proportional hazards regression analyses, adjusted for age, ethnicity and income, in the overall population, and across ethnic and SES groups.
Results
The age-standardised incidence rate of OHCA was lower in women than in men (30.9 versus 87.3 per 100,000 person-years), corresponding with a hazard ratio (HR) of 0.33 (95% confidence interval [CI] 0.31-0.35). These sex differences in hazard for OHCA existed in all income quintiles (HR range: 0.30-0.35) and ethnic groups (HR range: 0.19-0.40), except among Moroccans (HR 0.89, 95% CI 0.51-1.57).
Conclusion
Women have a substantial, yet lower OHCA incidence rate than men. The magnitude of these sex differences did not vary across social strata.

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

Int J Cardiol: 14 Nov 2021; 343:156-161
Bolijn R, Sieben CHAM, Kunst AE, Blom M, Tan HL, van Valkengoed IGM
Int J Cardiol: 14 Nov 2021; 343:156-161 | PMID: 34509532
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Impact:
Abstract

Long term outcomes in patients with RF/RHD: Eight-year follow-up of HP-RF/RHD (Himachal Pradesh Rheumatic Fever/Rheumatic Heart Disease) registry in a Northern Indian state.

Negi PC, Mahajan K, Kondal D, Asotra S, ... Merwaha R, Sharma R
Background
The long-term outcome data in patients with rheumatic fever/rheumatic heart disease (RF/RHD) is limited. We report the cumulative incidence of adverse outcomes in a cohort of RHD patients from a northern state of India at a median follow-up of 5.4 years.
Methods
1714 patients with RF/RHD diagnosed using clinical and echocardiographic criteria were registered from 2011 to 2018, and their baseline clinical characteristics and treatment practices were recorded. Patients were followed up annually for a median of 5.4 years (range 1-8 years) for incident adverse outcomes. The cumulative incidence of adverse composite outcomes, all-cause mortality, hospitalization for heart failure, stroke, and/or peripheral embolism was estimated. The baseline clinical characteristics were explored to identify the potential risk predictors using a multivariate cox proportional hazard model.
Results
The cumulative incidence of adverse composite outcomes was 17.1% (15.3%-19.0%) at a median follow-up of 5.4 years. The predictors for the adverse composite outcomes (hazard ratio, 95% confidence interval) were age (1.03, 1.02-1.04), education status below primary level (1.60, 1.23-2.05), severe valvular heart disease (1.74, 1.36-2.23), NYHA class III/IV at enrollment (1.56, 1.18-2.07), right heart failure (4.48, 2.85-6.95), history of stroke and/or peripheral embolism (3.7, 1.5-9.2) and mitral balloon valvuloplasty (0.62, 0.40-0.96).
Conclusions
The incidence of adverse outcomes is substantial in patients with RF/RHD. Thus, early detection of high-risk patients and their risk management is needed to improve outcomes.

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

Int J Cardiol: 14 Nov 2021; 343:149-155
Negi PC, Mahajan K, Kondal D, Asotra S, ... Merwaha R, Sharma R
Int J Cardiol: 14 Nov 2021; 343:149-155 | PMID: 34520796
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Impact:
Abstract

Impact of sex on outcomes after cardiac surgery: A systematic review and meta-analysis.

Dixon LK, Di Tommaso E, Dimagli A, Sinha S, ... Benedetto U, Angelini GD
Background
Despite advances in cardiac surgery, observational studies suggest that females have poorer post-operative outcomes than males. This study is the first to review sex related outcomes following both coronary artery bypass graft (CABG) and valve surgery with or without combined CABG.
Methods
We identified 30 primary research articles reporting either short-term mortality (in-hospital/30 day), long-term mortality, and post-operative stroke, sternal wound infection and myocardial infarction (MI) in both sexes following CABG and valve surgery with or without combined CABG. Reported adjusted odds/hazard ratio were pooled using an inverse variance model.
Results
Females undergoing CABG and combined valve and CABG surgery were at higher risk of short-term mortality (odds ratio (OR) 1.40; 95% confidence interval (CI) 1.32-1.49; I2 = 79%) and post-operative stroke (OR 1.2; CI 1.07-1.34; I2 = 90%) when compared to males. However, for isolated AVR, there was no difference found (OR 1.19; 95% CI 0.74-1.89). There was no increased risk in long-term mortality (OR 1.04; 95% CI: 0.93-1.16; I2 = 82%), post-operative MI (OR 1.22; 95%CI: 0.89-1.67; I2 = 60%) or deep sternal wound infection (OR 0.92; 95%CI: 0.65-1.03, I2 = 87%). No evidence of publication bias or small study effect was found.
Conclusion
Females are at a greater risk of short-term mortality and post-operative stroke than males following CABG and valve surgery combined with CABG. However, there is no difference for Isolated AVR. Long-term mortality is equivalent in both sexes. PROSPERO Registration: CRD42021244603.

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

Int J Cardiol: 14 Nov 2021; 343:27-34
Dixon LK, Di Tommaso E, Dimagli A, Sinha S, ... Benedetto U, Angelini GD
Int J Cardiol: 14 Nov 2021; 343:27-34 | PMID: 34520795
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Impact:
Abstract

Changing age-specific trends in incidence, comorbidities and mortality of hospitalised heart failure in Western Australia between 2001 and 2016.

Weber C, Hung J, Hickling S, Li I, Murray K, Briffa T
Background
Incident heart failure (HF) hospitalisation rates in most high-income countries are stable or declining. However, HF incidence may be increasing in younger people linked to changing risk factor profiles in the general population. We examined age and sex-specific patterns of incidence, comorbidities and mortality of hospitalised HF in Western Australia (WA) between 2001 and 2016.
Methods and results
All WA residents aged 25-94 years, with an incident (first-ever) principal HF discharge diagnosis between 2001 and 2016 were included (n = 22,476). Poisson regression derived annual age and sex-standardised rates of incident HF and 1-year mortality overall, and by age groups (25-54, 55-74, 75-94), across the study period. Overall, the age and sex-standardised rates of incident HF increased marginally by 0.6% per year (95% confidence interval (CI), 0.3, 0.8) whereas incidence increased by 3.1% per year (95% CI, 2.2, 4.0) in the 25-54 year age-group (trend p < 0.0001). There was a high prevalence (≥15%) of obesity, diabetes mellitus, cardiomyopathy, hypertension, ischemic heart disease, atrial fibrillation, and chronic kidney disease in younger HF patients. Overall standardised 1-year mortality declined by -1.0% per year (95%CI, -0.4, -1.6), driven largely by the mortality decline in the 55-74 year age group.
Conclusion
Incident HF hospitalisation rates have been rising in WA since 2006, notably in individuals under 55 years. The underlying reasons require further investigation, particularly the population-attributable risk related to increasing obesity and diabetes mellitus in the general population. Rising HF incidence along with declining mortality rates portends to an increasing HF burden in the community.

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

Int J Cardiol: 14 Nov 2021; 343:56-62
Weber C, Hung J, Hickling S, Li I, Murray K, Briffa T
Int J Cardiol: 14 Nov 2021; 343:56-62 | PMID: 34520794
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Impact:
Abstract

To what extent are comorbidity profiles associated with referral and uptake to cardiac rehabilitation.

Tang LH, Harrison A, Skou ST, Doherty P
Introduction
Given the high proportion of comorbidities in patients with coronary heart disease (CHD) and low participation rates in cardiac rehabilitation (CR), a better understanding of how comorbidity interacts with the CR pathway is needed. We investigated associations between comorbidity profiles and referral and uptake in everyday clinical CR across UK.
Method
Patients (≥18 years) diagnosed with a CHD between 1st of January 2014 and 31st of December 2019 registered in the National Audit of Cardiac Rehabilitation (NACR) database were eligible. Self-reported comorbidities from 15 disease categories were conceptualized into similar or dissimilar based on overall related pathophysiologic profile and care management as CHD. Regression models were conducted with four comorbidity profiles; similar conditions, dissimilar conditions, similar and dissimilar and no comorbidity.
Results
399,348 (61.8%) patients were eligible for referral from 198 programmes. The majority were males (70%), mean age of 67 (±12 SD) years. A non-significant association was found between comorbidity profiles and referral. Odds ratios (OR) for CR uptake were higher in patients with dissimilar (OR = 1.38 (95% CI 1.26-1.54)) and dissimilar and similar comorbidities profiles (OR = 1.35 (95% CI 1.21-1.43)) compared to patients with similar comorbidities. No significant differences in uptake were found between patients with similar comorbidities and those without comorbidities (OR = 0.985 (95% CI 0.854-1.125).
Conclusion
Using routine practice data, comorbidity profiles were not significantly associated with CR referral suggesting equality in referral. Dissimilar comorbidity profiles were associated with uptake. To increase the likelihood of starting CR, services should consider developing tailored participation strategies that include comorbidity profiles.

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

Int J Cardiol: 14 Nov 2021; 343:85-91
Tang LH, Harrison A, Skou ST, Doherty P
Int J Cardiol: 14 Nov 2021; 343:85-91 | PMID: 34534605
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Impact:
Abstract

Associations between cardiorespiratory fitness, sex and long term mortality amongst adults undergoing exercise treadmill testing.

Harb SC, Wang TKM, Cremer PC, Wu Y, ... Menon V, Jaber WA
Background
Cardiorespiratory fitness (CRF) varies with sex and is an independent predictor of mortality. We sought to investigate sex differences in the exercise protocol selected, CRF levels, and their relationships with long term all-cause mortality.
Methods
In a 25-year stress testing registry spanning from 1991 to 2014, consecutive all-comer patients who underwent exercise stress testing at Cleveland Clinic were categorized by sex, stress protocol and imaging modality. All tests were conducted by one or more of stress test technicians, sonographers and nuclear medicine technologists, and interpreted by cardiologists. The primary outcome all-cause mortality was analyzed in using multivariable Cox regression.
Results
In 120,705 patients, the mean age was 53.3 ± 12.5 years, and 41% were female. Females were more commonly referred for non-Bruce exercise protocols (modified Bruce, Cornell 0, 5 and 10, Naughton and modified Naughton) with odds ratio of 2.62; 95% confidence interval (95%CI) (2.54-2.70) after adjusting for age and comorbidities. When also adjusting for the protocol chosen, females achieved lower CRF with beta -1.40, 95% CI (-1.43, -1.37). There were 8426 (6.9%) deaths during a mean follow-up of 8.7 years. Both female sex and CRF were independently associated with lower all-cause mortality with hazards ratio (95%CI) of 0.44 (0.41-0.46) and 0.41 (0.39-0.42) respectively, after adjusting for age, co-morbidities and protocol chosen.
Conclusions
Women were more likely referred for less demanding exercise protocols, more imaging protocols and achieved lower CRF than men. Despite this, female sex was associated with significantly lower long term mortality for equivalent CRF level in adjusted analyses.

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

Int J Cardiol: 31 Oct 2021; 342:103-107
Harb SC, Wang TKM, Cremer PC, Wu Y, ... Menon V, Jaber WA
Int J Cardiol: 31 Oct 2021; 342:103-107 | PMID: 34363868
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Impact:
Abstract

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

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

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 31 Oct 2021; 342:34-38
Gonzaga LRA, Gomes WJ, Rocco IS, Matos-Garcia BC, ... Arena R, Guizilini S
Int J Cardiol: 31 Oct 2021; 342:34-38 | PMID: 34171450
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Impact:
Abstract

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

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

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

Int J Cardiol: 31 Oct 2021; 342:1-6
Shah P, Jimenez-Ruiz A, Gibson A, Vargas-González JC, ... Bagur R, Sposato LA
Int J Cardiol: 31 Oct 2021; 342:1-6 | PMID: 34245792
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Impact:
Abstract

LncRNA HCP5 in hBMSC-derived exosomes alleviates myocardial ischemia reperfusion injury by sponging miR-497 to activate IGF1/PI3K/AKT pathway.

Li KS, Bai Y, Li J, Li SL, ... Zhou Q, Wang DJ
Ischemia/reperfusion (I/R) injury is an inevitable process during heart transplant and suppressing I/R injury could greatly improve the survival rate of recipients. Mesenchymal stem cells (MSCs) have positive effects on I/R. We aimed to investigate the mechanisms underlying the protective roles of MSCs in I/R. Both cell model and rat model of myocardial I/R were used. MTT assay and flow cytometry were used to measure cell viability and apoptosis, respectively. QRT-PCR and western blotting were employed to measure levels of lncRNA HCP5 (HLA complex P5), miR-497, apoptosis-related proteins, and insulin-like growth factor (IGF1)/PI3K/AKT pathway. Dual luciferase assay was used to validate interactions of HCP5 and miR-497, miR-497 and IGF1. Echocardiography was performed to evaluate cardiac function of rats. Serum levels of CK-MB and LDH were measured. H&E and Masson staining were used to examine morphology of myocardial tissues. hBMSC-derived exosomes (hBMSC-Exos) increased the viability of cardiomyocytes following hypoxia/reperfusion (H/R) and decreased apoptosis. H/R diminished HCP5 expression in cardiomyocytes while hBMSC-Exos recovered the level. Overexpression of HCP5 in hBMSC-Exos further enhanced the protective effects in H/R while HCP5 knockdown suppressed. HCP5 directly bound miR-497 and miR-497 targeted IGF1. miR-497 mimics or si-IGF1 blocked the effects of HCP5 overexpression. Further, hBMSC-Exos alleviated I/R injury in vivo and knockdown of HCP5 in hBMSC-Exos decreased the beneficial effects. AntagomiR-497 blocked the effects of HCP5 knockdown. HCP5 from hBMSC-Exos protects cardiomyocytes against I/R injury via sponging miR-497 to disinhibit IGF1/PI3K/AKT pathway. These results shed light on mechanisms underlying the protective role of hBMSC-Exos in I/R.

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

Int J Cardiol: 31 Oct 2021; 342:72-81
Li KS, Bai Y, Li J, Li SL, ... Zhou Q, Wang DJ
Int J Cardiol: 31 Oct 2021; 342:72-81 | PMID: 34311013
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Impact:
Abstract

Clopidogrel, prasugrel, and ticagrelor for all-comers with ST-segment elevation myocardial infarction.

Jacobsen MR, Engstrøm T, Torp-Pedersen C, Gislason G, ... Jabbari R, Sørensen R
Background
To compare effectiveness and safety of clopidogrel, prasugrel, and ticagrelor among all-comers with ST-segment elevation myocardial infarction (STEMI) and extend the knowledge from randomized clinical trials.
Methods
All consecutive patients with STEMI admitted to Copenhagen University Hospital, Rigshospitalet, from 2009 to 2016 were identified via the Eastern Danish Heart Registry. By individual linkage to Danish nationwide registries, claimed drugs and end points were obtained. Patients alive a week post-discharge were included, stratified according to clopidogrel, prasugrel, or ticagrelor treatment, and followed for a year. The effectiveness end point (a composite of all-cause mortality, recurrent myocardial infarction, and ischemic stroke) and safety end point (a composite of bleedings leading to hospitalization) were assessed by multivariate Cox proportional-hazards models.
Results
In total, 5123 patients were included (clopidogrel [1245], prasugrel [1902], ticagrelor [1976]) with ≥95% treatment persistency. Concomitant use of aspirin was ≥95%. Females accounted for 24% and elderly for 17%. Compared with clopidogrel, the effectiveness end point occurred less often for ticagrelor (HR 0.50, 95% CI 0.35-0.70) and prasugrel (HR 0.48, 95% CI 0.33-0.68) without differences in bleedings leading to hospitalization. No differences in comparative effectiveness or safety were found between prasugrel and ticagrelor. Sensitivity analyses with time-dependent drug exposure and the period 2011-2015 showed similar results.
Conclusions
Among all-comers with STEMI, ticagrelor and prasugrel were associated with reduced incidence of the composite end point of all-cause mortality, recurrent myocardial infarction, and ischemic stroke without an increase in bleedings leading to hospitalization compared with clopidogrel. No differences were found between prasugrel and ticagrelor.

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

Int J Cardiol: 31 Oct 2021; 342:15-22
Jacobsen MR, Engstrøm T, Torp-Pedersen C, Gislason G, ... Jabbari R, Sørensen R
Int J Cardiol: 31 Oct 2021; 342:15-22 | PMID: 34311012
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Impact:
Abstract

Strain echocardiography improves prediction of arrhythmic events in ischemic and non-ischemic dilated cardiomyopathy.

Melichova D, Nguyen TM, Salte IM, Klaeboe LG, ... Brunvand H, Haugaa KH
Background
Recent evidence suggests that an implantable cardioverter defibrillator (ICD) in non-ischemic cardiomyopathy (NICM) may not offer mortality benefit. We aimed to investigate if etiology of heart failure and strain echocardiography can improve risk stratification of life threatening ventricular arrhythmia (VA) in heart failure patients.
Methods
This prospective multi-center follow-up study consecutively included NICM and ischemic cardiomyopathy (ICM) patients with left ventricular ejection fraction (LVEF) <40%. We assessed LVEF, global longitudinal strain (GLS) and mechanical dispersion (MD) by echocardiography. Ventricular arrhythmia was defined as sustained ventricular tachycardia, sudden cardiac death or appropriate shock from an ICD.
Results
We included 290 patients (67 ± 13 years old, 74% males, 207(71%) ICM). During 22 ± 12 months follow up, VA occurred in 32(11%) patients. MD and GLS were both markers of VA in patients with ICM and NICM, whereas LVEF was not (p = 0.14). MD independently predicted VA (HR: 1.19; 95% CI 1.08-1.32, p = 0.001), with excellent arrhythmia free survival in patients with MD <70 ms (Log rank p < 0.001). Patients with NICM and MD <70 ms had the lowest VA incidence with an event rate of 3%/year, while patients with ICM and MD >70 ms had highest VA incidence with an event rate of 16%/year.
Conclusion
Patients with NICM and normal MD had low arrhythmic event rate, comparable to the general population. Patients with ICM and MD >70 ms had the highest risk of VA. Combining heart failure etiology and strain echocardiography may classify heart failure patients in low, intermediate and high risk of VA and thereby aid ICD decision strategies.

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

Int J Cardiol: 31 Oct 2021; 342:56-62
Melichova D, Nguyen TM, Salte IM, Klaeboe LG, ... Brunvand H, Haugaa KH
Int J Cardiol: 31 Oct 2021; 342:56-62 | PMID: 34324947
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Impact:
Abstract

Cardiac Contractility Modulation in Patients with Ischemic versus Non-ischemic Cardiomyopathy: Results from the MAINTAINED Observational Study.

Fastner C, Yuecel G, Rudic B, Schmiel G, ... Akin I, Kuschyk J
Background
Cardiac contractility modulation (CCM) is an FDA-approved device-based therapy for patients with systolic heart failure and normal QRS width who are symptomatic despite optimal drug therapy. The purpose of this study was to compare the long-term therapeutic effects of CCM therapy in patients with ischemic (ICM) versus non-ischemic cardiomyopathy (NICM).
Methods
Changes in NYHA class, KDIGO CKD stage, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and NT-proBNP levels were compared as functional parameters. Moreover, observed mortality rates at 1 and 3 years were compared to those predicted by the MAGGIC heart failure risk score, and observed mortality rates were compared between groups for the entire follow-up period.
Results
One hundred and seventy-four consecutive patients with chronic heart failure and CCM device implantation between 2002 and 2019 were included in this retrospective analysis. LVEF was significantly higher in NICM patients after 3 years of CCM therapy (35 ± 9 vs. 30 ± 9%; p = 0.0211), and after 5 years, also TAPSE of NICM patients was significantly higher (21 ± 5 vs. 18 ± 5%; p = 0.0437). There were no differences in other effectiveness parameters. Over the entire follow-up period, 35% of all patients died (p = 0.81); only in ICM patients, mortality was lower than predicted at 3 years (35 vs. 43%, p = 0.0395).
Conclusions
Regarding improvement of biventricular systolic function, patients with NICM appear to benefit particularly from CCM therapy.

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

Int J Cardiol: 31 Oct 2021; 342:49-55
Fastner C, Yuecel G, Rudic B, Schmiel G, ... Akin I, Kuschyk J
Int J Cardiol: 31 Oct 2021; 342:49-55 | PMID: 34329680
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Impact:
Abstract

The association of air pollutants exposure with subclinical inflammation and carotid atherosclerosis.

Oikonomou E, Lazaros G, Mystakidi VC, Papaioannou N, ... Kaski JC, Tousoulis D
Background
Air pollution is a well-described environmental factor with evidence suggesting a firm association with cardiovascular diseases. The purpose of this study was to determine the association of exposure to gaseous air pollutants on atherosclerosis burden.
Methods
1955 inhabitants of the Corinthia region, aged 40 years or older, underwent clinical and biochemical assessment as well as carotid ultrasonography to evaluate carotid intima-media thickness (cIMT) and plaque burden. Analyzers recording time series concentration of CO, NO2, and SO2 were located at 4 different open sites (Regions 1, 2, 3 and 4) based on their proximity to industries, highways or shipyards.
Results
A higher concentration of CO, NO2, and SO2 was observed in Region 4 compared to the other regions. Mean cIMT (Region 1: 0.93 ± 0.24 mm; Region 2: 0.96 ± 0.40 mm; Region 3: 0.94 ± 0.39 mm; Region 4: 1.14 ± 0.55 mm, p < 0.001), maximum cIMT (p < 0.001) as well as carotid plaque burden (Region 1: 13.3%; Region 2: 18.8%; Region 3: 22.4%; Region 4: 38.6%, p < 0.001) were significantly higher in individuals of Region 4. Inhabitants of Region 4 had also higher levels of C reactive protein (Region 1: 4.56 ± 4.85 mg/l; Region 2: 3.49 ± 4.46 mg/l; Region 3: 4.03 ± 3.32 mg/l, Region 4: 5.16 ± 8.26 mg/l, p < 0.001). Propensity score analysis revealed higher inter-area differences in mean cIMT of individuals with coronary artery disease (CAD) (high vs low air pollution area: 1.56 ± 0.80 mm; vs. 1.18 ± 0.54 mm, p < 0.001) while there was no difference in cIMT of the matched population without CAD (p = 0.52).
Conclusions
An increased carotid atherosclerotic and inflammatory burden is observed in inhabitants of areas with the highest concentration of air pollutants.

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

Int J Cardiol: 31 Oct 2021; 342:108-114
Oikonomou E, Lazaros G, Mystakidi VC, Papaioannou N, ... Kaski JC, Tousoulis D
Int J Cardiol: 31 Oct 2021; 342:108-114 | PMID: 34339768
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Impact:
Abstract

Cardiovascular manifestations in hospitalized patients with hemochromatosis in the United States.

Udani K, Chris-Olaiya A, Ohadugha C, Malik A, Sansbury J, Paari D
Background
Heart complications are the main cause of morbidity and mortality in hemochromatosis, but the liver is the main site for iron deposition in these patients. Large multicenter studies have described cardiovascular (CV) manifestations in patients with secondary hemochromatosis. However, the overall prevalence and risk of CV manifestations in patients with hemochromatosis at the population level are unknown.
Objective
To examine the prevalence and risk of CV manifestations in patients with hemochromatosis.
Methods
A retrospective cohort from the National Inpatient Sample database between 2012 and 2014 was studied. We identified hemochromatosis using ICD-9-CM diagnostic codes. CV manifestations were defined by the presence of conduction disorders, arrhythmias, congestive heart failure (CHF), pulmonary hypertension, and non-ischemic cardiomyopathy (NISCM).
Results
Of the 63,846,188 weighted hospitalizations that met the inclusion criteria, 64,590 (0.1%) had hemochromatosis and 13,200,000 (20.7%) had one or more CV manifestations. Of those with hemochromatosis, 5.3% had primary and 94.7% had secondary hemochromatosis. 27.8% of all hemochromatosis patients had one or more CV manifestations, 16% cardiac arrhythmias, 10.6% supraventricular arrhythmias (SVA), 0.8% ventricular arrhythmias, 9.3% CHF, 7.4% pulmonary hypertension, 4.2% NISCM, 2% conduction disorders, and 0.4% cardiac arrest. SVA (14.6% vs 10.4%, P < 0.001) was more prevalent in primary hemochromatosis compared to secondary while pulmonary hypertension (7.7% vs 2.6%, P < 0.001) was more prevalent in secondary hemochromatosis compared to primary. In multivariate modelling, only the adjusted odds of composite CV manifestations (odds ratio [OR] 1.24, 95% confidence interval [CI]: 1.03-1.48, P < 0.05) and SVA (OR 1.59, 95% CI: 1.28-1.96, P < 0.001) were significantly higher in patients with primary hemochromatosis compared with patients without hemochromatosis. In patients with secondary hemochromatosis, the adjusted odds of composite CV manifestations (OR 1.84, 95% CI: 1.74-1.95, P < 0.001), CHF (OR 1.46, 95% CI: 1.35-1.57, P < 0.001), conduction disorder (OR 1.52, 95% CI: 1.33-1.73, P < 0.001), pulmonary hypertension (OR 4.43, 95% CI: 3.97-4.94, P < 0.001), SVA (OR 1.39, 95% CI: 1.29-1.48, P < 0.001), and NISCM (OR 1.98, 95% CI: 1.79-2.20, P < 0.001) were significantly higher compared with patients without hemochromatosis.
Conclusion
Supraventricular arrhythmias, congestive heart failure, and pulmonary hypertension were the most common CV disorders in hemochromatosis patients. Risk-adjusted burden of supraventricular arrhythmias was significantly higher in primary and secondary hemochromatosis while patients with secondary hemochromatosis had a higher risk of congestive heart failure, pulmonary hypertension, conduction disorders, and non-ischemic cardiomyopathy.

Published by Elsevier B.V.

Int J Cardiol: 31 Oct 2021; 342:117-124
Udani K, Chris-Olaiya A, Ohadugha C, Malik A, Sansbury J, Paari D
Int J Cardiol: 31 Oct 2021; 342:117-124 | PMID: 34343533
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Impact:
Abstract

Comparing invasive hemodynamic responses in adenosine hyperemia versus physical exercise stress in chronic coronary syndromes.

Cook CM, Howard JP, Ahmad Y, Shun-Shin MJ, ... Francis DP, Davies JE
Objectives
Adenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis.
Methods
Twenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli.
Results
Mean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44-0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm-1.sec-1 vs 4.2 ± 1.7 mmHg.cm-1.sec-1, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa, MR, HR, RPP and APV during IV adenosine hyperemia versus exercise were all significantly different (p < 0.05 for all).
Conclusions
In patients with CCS and coronary stenosis, invasive hemodynamic responses differed markedly between IV adenosine hyperemia versus physical exercise stress. These differences were observed across systemic, coronary and microcirculatory hemodynamics.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 31 Oct 2021; 342:7-14
Cook CM, Howard JP, Ahmad Y, Shun-Shin MJ, ... Francis DP, Davies JE
Int J Cardiol: 31 Oct 2021; 342:7-14 | PMID: 34358553
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Impact:
Abstract

Thirty-day outcomes and predictors of mortality following acute myocardial infarction in northern Tanzania: A prospective observational cohort study.

Goli S, Sakita FM, Kweka GL, Tarimo TG, ... Limkakeng AT, Hertz JT
Objective
There is a rising burden of myocardial infarction (MI) within sub-Saharan Africa. Prospective studies of detailed MI outcomes in the region are lacking.
Methods
Adult patients with confirmed MI from a prospective surveillance study in northern Tanzania were enrolled in a longitudinal cohort study after baseline health history, medication use, and sociodemographic data were obtained. Thirty days following hospital presentation, symptom status, rehospitalizations, medication use, and mortality were assessed via telephone or in-person interviews using a standardized follow-up questionnaire. Multivariate logistic regression was performed to identify baseline predictors of thirty-day mortality.
Results
Thirty-day follow-up was achieved for 150 (98.7%) of 152 enrolled participants. Of these, 85 (56.7%) survived to thirty-day follow-up. Of the surviving participants, 71 (83.5%) reported persistent anginal symptoms, four (4.7%) reported taking aspirin regularly, seven (8.2%) were able to identify MI as the reason for their hospitalization, and 17 (20.0%) had unscheduled rehospitalizations. Self-reported history of diabetes at baseline (OR 0.32, 95% CI 0.10-0.89, p = 0.04), self-reported history of hypertension at baseline (OR 0.34, 95% CI 0.15-0.74, p = 0.01), and antiplatelet use at initial presentation (OR 0.19, 95% CI 0.04-0.65, p = 0.02) were all associated with lower odds of thirty-day mortality.
Conclusions
In northern Tanzania, thirty-day outcomes following acute MI are poor, and mortality is associated with self-awareness of comorbidities and medication usage. Further investigation is needed to develop interventions to improve care and outcomes of MI in Tanzania.

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

Int J Cardiol: 31 Oct 2021; 342:23-28
Goli S, Sakita FM, Kweka GL, Tarimo TG, ... Limkakeng AT, Hertz JT
Int J Cardiol: 31 Oct 2021; 342:23-28 | PMID: 34364908
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Impact:
Abstract

Performance of the HFPEF and the HFA-PEFF scores for the diagnosis of heart failure with preserved ejection fraction in Japanese patients: A report from the Japanese multicenter registry.

Tada A, Nagai T, Omote K, Iwano H, ... Saito Y, Anzai T
Background
Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Although the H2FPEF score and HFA-PEFF algorithm have been proposed for diagnosing HFpEF, previous validation studies were conducted in stable chronic heart failure (HF). Moreover, information on their applicability in the Asian population is limited. We sought to investigate these scores\' diagnostic performance for HFpEF in Japanese patients recently hospitalized due to acute decompensated HF.
Methods
We examined patients with HFpEF recently hospitalized with acute decompensated HF from a nationwide HFpEF-specific multicenter registry (HFpEF group) and control patients who underwent echocardiography to investigate the cause of dyspnea in our hospital (Non-HFpEF group).
Results
The studied population included 372 patients (194 HFpEF group and 178 Non-HFpEF group; HFpEF prevalence, 52%). A high H2FPEF score (6-9 points) could diagnose HFpEF with a high specificity of 97% and a positive predictive value (PPV) of 94%, and a low H2FPEF score (0-1 point) could rule out HFpEF with a high sensitivity of 97% and a negative predictive value (NPV) of 93%. HFpEF could be diagnosed with a high HFA-PEFF score (5-6 points) (specificity, 84%; PPV, 82%) or ruled out with a low HFA-PEFF score (0-1 point) (sensitivity, 99%; NPV, 89%). The H2FPEF score was significantly superior to the HFA-PEFF score in diagnostic accuracy (area under the curve: 0.89 vs. 0.82, respectively, p = 0.004).
Conclusions
The H2FPEF and the HFA-PEFF scores had acceptable diagnostic accuracy in diagnosing HFpEF in Japanese patients.

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

Int J Cardiol: 31 Oct 2021; 342:43-48
Tada A, Nagai T, Omote K, Iwano H, ... Saito Y, Anzai T
Int J Cardiol: 31 Oct 2021; 342:43-48 | PMID: 34364907
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Impact:
Abstract

Characteristics and outcomes of MitraClip in octogenarians: Evidence from 1853 patients in the GIOTTO registry.

Giordano A, Biondi-Zoccai G, Finizio F, Ferraro P, ... Castriota F, Tamburino C
Background
We aimed at appraising features and outcomes of patients undergoing MitraClip treatment according to their age.
Methods
We queried the prospective GIse registry Of Transcatheter treatment of mitral valve regurgitaTiOn (GIOTTO) multicenter registry dataset including 19 Italian centers performing MitraClip implantation, distinguishing patients <80 vs ≥80 years of age.
Results
In total, 1853 patients were included, 751 (40.5%) octogenarians and 1102 (59.5%) non-octogenarians. Several baseline and procedural features were significantly different, including gender, regurgitation etiology, and functional class (all p < 0.05). In-hospital outcomes were similarly satisfactory, with death occurring in 18 (2.4%) and 32 (2.9%, p = 0.561), respectively, and improvement in mitral regurgitation in 732 (97.4%) and 1078 (97.8%, p = 0.746), respectively. After a mean follow-up of 15 months, death occurred in 152 (20.2%) and 264 (24.0%), and cardiac death in 85 (11.3%) and 138 (12.5%), respectively (both p > 0.05). Rehospitalization for heart failure and the composite of cardiac death or rehospitalization for heart failure were significantly less common in octogenarians: 63 (8.4%) vs 156 (14.2%, p < 0.001), and 125 (16.6%) vs 242 (22.0%, p = 0.005), respectively. Multivariable analysis showed that these differences were largely due to confounding features, as after adjustment for baseline, clinical and imaging characteristics no significant difference was found for the above clinical endpoints.
Conclusions
Transcatheter mitral valve repair with the MitraClip in carefully selected octogenarians appears feasible and safe, and is associated with favorable clinical outcomes at mid-term follow-up.

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

Int J Cardiol: 31 Oct 2021; 342:65-71
Giordano A, Biondi-Zoccai G, Finizio F, Ferraro P, ... Castriota F, Tamburino C
Int J Cardiol: 31 Oct 2021; 342:65-71 | PMID: 34375704
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Impact:
Abstract

Protection of the enhanced Nrf2 deacetylation and its downstream transcriptional activity by SIRT1 in myocardial ischemia/reperfusion injury.

Xu JJ, Cui J, Lin Q, Chen XY, ... Wei B, Zhao W
Nrf2, the master gene transcriptor of antioxidant proteins, and SIRT1, the unique Class III histone deacetylase of sirtuins, have been involved in protecting myocardial ischemia/reperfusion (MI/R) injury. However, whether the protective effect of SIRT1 is directly related to the deacetylation of Nrf2 in the pathology of MI/R remains to be investigated. The current study was designed to evaluate the regulation of Nrf2 deacetylation and transcriptional activity by SIRT1 in MI/R. Hypoxia/reoxygenation (H/R) cardiomyocytes and MI/R mice were used to assess the role of SIRT1 in Nrf2 activation. Oxidative stress, cardiac function, LDH release, ROS and infarct size were also evaluated. We found that Nrf2 physically interacted with SIRT1 not only in normal and H/R cardiomyocytes in vitro, but also in Sham or I/R hearts in vivo. Adenovirus induced SIRT1 overexpression resulted in protected H/R induced cell death, accompanied by declined LDH release. Through MI/R in vivo, cardiac overexpression of SIRT1 led to ameliorated cardiac function and infarct size, as well as the decreased cardiac oxidative stress. Notably, such beneficial actions of SIRT1 were blocked by the Nrf2 silence. Mechanically, acetylation of Nrf2 was significantly decreased by SIRT1 overexpression in cardiomyocytes or in whole hearts, which upregulated the downstream signaling pathway of Nrf2. Taken together, we uncovered a clue, for the first time that SIRT1 physically interacts with Nrf2. The cardioprotective effect of SIRT1 overexpression against MI/R is associated with the increased Nrf2 deacetylation and activity. These findings have offered a direct proof and new perspective of post-translational modification in the understanding of oxidative stress and MI/R treatment.

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

Int J Cardiol: 31 Oct 2021; 342:82-93
Xu JJ, Cui J, Lin Q, Chen XY, ... Wei B, Zhao W
Int J Cardiol: 31 Oct 2021; 342:82-93 | PMID: 34403762
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Impact:
Abstract

Neuropeptide Y promotes adipogenesis of human cardiac mesenchymal stromal cells in arrhythmogenic cardiomyopathy.

Stadiotti I, Di Bona A, Pilato CA, Scalco A, ... Mongillo M, Zaglia T
Background
Arrhythmogenic Cardiomyopathy (AC) is a familial cardiac disease, mainly caused by mutations in desmosomal genes. AC hearts show fibro-fatty myocardial replacement, which favors stress-related life-threatening arrhythmias, predominantly in the young and athletes. AC lacks effective therapies, as its pathogenesis is poorly understood. Recently, we showed that cardiac Mesenchymal Stromal Cells (cMSCs) contribute to adipose tissue in human AC hearts, although the underlying mechanisms are still unclear.
Purpose
We hypothesize that the sympathetic neurotransmitter, Neuropeptide Y (NPY), participates to cMSC adipogenesis in human AC.
Methods
For translation of our findings, we combined in vitro cytochemical, molecular and pharmacologic assays on human cMSCs, from myocardial biopsies of healthy controls and AC patients, with the use of existing drugs to interfere with the predicted AC mechanisms. Sympathetic innervation was inspected in human autoptic heart samples, and NPY plasma levels measured in healthy and AC subjects.
Results
AC cMSCs expressed higher levels of pro-adipogenic isotypes of NPY-receptors (i.e. Y1-R, Y5-R). Consistently, NPY enhanced adipogenesis in AC cMSCs, which was blocked by FDA-approved Y1-R and Y5-R antagonists. AC-associated PKP2 reduction directly caused NPY-dependent adipogenesis in cMSCs. In support of the involvement of sympathetic neurons (SNs) and NPY in AC myocardial remodeling, patients had elevated NPY plasma levels and, in human AC hearts, SNs accumulated in fatty areas and were close to cMSCs.
Conclusions
Independently from the disease origin, AC causes in cMSCs a targetable gain of responsiveness to NPY, which leads to increased adipogenesis, thus playing a role in AC myocardial remodeling.

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

Int J Cardiol: 31 Oct 2021; 342:94-102
Stadiotti I, Di Bona A, Pilato CA, Scalco A, ... Mongillo M, Zaglia T
Int J Cardiol: 31 Oct 2021; 342:94-102 | PMID: 34400166
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Impact:
Abstract

In-vivo evidence of systemic endothelial vascular dysfunction in COVID-19.

Mejia-Renteria H, Travieso A, Sagir A, Martínez-Gómez E, ... Lerman A, Escaned J
Background
Endothelial dysfunction is one of the underlying mechanisms to vascular and cardiac complications in patients with COVID-19. We sought to investigate the systemic vascular endothelial function and its temporal changes in COVID-19 patients from a non-invasive approach with reactive hyperemia peripheral arterial tonometry (PAT).
Methods
This is a prospective, observational, case-control and blinded study. The population was comprised by 3 groups: patients investigated during acute COVID-19 (group 1), patients investigated during past COVID-19 (group 2), and controls 1:1 matched to COVID-19 patients by demographics and cardiovascular risk factors (group 3). The natural logarithmic scaled reactive hyperemia index (LnRHI), a measure of endothelium-mediated dilation of peripheral arteries, was obtained in all the participants and compared between study groups.
Results
144 participants were enrolled (72 COVID-19 patients and 72 matched controls). Median time from COVID-19 symptoms to PAT assessment was 9.5 and 101.5 days in groups 1 and 2, respectively. LnRHI was significantly lower in group 2 compared to both group 1 and controls (0.53 ± 0.23 group 2 vs. 0.72 ± 0.26 group 1, p = 0.0043; and 0.79 ± 0.23 in group 3, p < 0.0001). In addition, within group 1, it was observed a markedly decrease in LnRHI from acute COVID-19 to post infection stage (0.73 ± 0.23 vs. 0.42 ± 0.26, p = 0.0042).
Conclusions
This study suggests a deleterious effect of SARS-CoV-2 infection on systemic vascular endothelial function. These findings open new venues to investigate the clinical implication and prognostic role of vascular endothelial dysfunction in COVID-19 patients and post-COVID syndrome using non-invasive techniques.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 23 Oct 2021; epub ahead of print
Mejia-Renteria H, Travieso A, Sagir A, Martínez-Gómez E, ... Lerman A, Escaned J
Int J Cardiol: 23 Oct 2021; epub ahead of print | PMID: 34706286
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Impact:
Abstract

Mechanical complications in ST-elevation myocardial infarction: The impact of pre-hospital delay.

Bouisset F, Deney A, Ferrières J, Panagides V, ... Cayla G, MODIF registry investigators
Aims
Mechanical complications (MC) (i.e., free wall rupture (FWR), papillary muscle rupture (PMR) and ventricular septal rupture (VSR)) are rare complications of ST- elevation acute myocardial infarction (STEMI). Incidence of MC according to pre-hospital delay remains unknown. We aimed to determine the rates of MC according to pre-hospital delay.
Methods
Analysis was conducted on the MODIF registry data. Patients were allocated to four groups according to pre-hospital delay: 0 to 12 h, 12 to 24 h, 24 to 36 h and 36 to 48 h.
Results
6185 patients with complete data were analyzed. Mean age was 64.1 years old and 75.7% of patients were males. Eighty-three patients (1.34%) presented with MC: 44 (0.71%) experienced a FWR, 17 (0.27%) a PMR, and 22 (0.36%) a VSR. Global rates of MC were 0.82%, 1.43%, 1.24% and 5.07% in the four groups of pre-hospital delays - 0 to 12 h, 12 to 24 h, 24 to 36 h and 36 to 48 h - respectively (p < 0.001). In-hospital mortality rates were high: 44.2%, 47.1% and 54.6% for FWR, PMR and VSR, respectively. In multivariate analysis, factors independently related to the occurrence of MC were older age, female sex, simultaneous COVID-19 infection, absence of dyslipidemia, initial TIMI flow 0 or 1 in the culprit artery, 36 to 48 h-pre-hospital delay and absence of revascularization by percutaneous coronary intervention (PCI) with stent implantation.
Conclusion
The probability of MC in STEMI increases with pre-hospital delay. Mechanical complications of STEMI remain associated with a very poor prognosis.

Copyright © 2021 Elsevier Ireland Ltd. All rights reserved.

Int J Cardiol: 22 Oct 2021; epub ahead of print
Bouisset F, Deney A, Ferrières J, Panagides V, ... Cayla G, MODIF registry investigators
Int J Cardiol: 22 Oct 2021; epub ahead of print | PMID: 34699868
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Impact:
Abstract

Prevalence and clinical implications of eligibility criteria for prolonged dual antithrombotic therapy in patients with PEGASUS and COMPASS phenotypes: Insights from the START-ANTIPLATELET registry.

Cesaro A, Gragnano F, Calabrò P, Moscarella E, ... Marcucci R, START-ANTIPLATELET collaborators
Aim
To analyze the prevalence and clinical implications of the eligibility criteria for prolonged dual antithrombotic therapy with ticagrelor 60 mg twice daily and/or rivaroxaban 2.5 mg twice daily in a contemporary real-world ACS registry.
Methods
Patients from the START-ANTIPLATELET registry (NCT02219984) were stratified according to the eligibility criteria of the PEGASUS and COMPASS studies to investigate the proportion of patients eligible for prolonged dual antithrombotic therapy at discharge and after 1-year of DAPT. Net adverse clinical events (NACE), defined as all-cause death, myocardial infarction, stroke, and major bleeding, at 1 year were also evaluated and compared among groups.
Results
1844 were considered for the analysis at baseline. Out of 849 event-free patients continually receiving dual antiplatelet therapy for at least 1 year, 577 (68%) and 583 (68.7%) met at least one eligibility criterion for ticagrelor and rivaroxaban, respectively. In the PEGASUS-like patients, age was the most common criterion (71% of cases). The presence ≥2 cardiovascular risk factors was the most common eligibility criterion in the COMPASS-like patients (80.8%). At 1-year follow-up, 211 (11.4%) and 119 (6.5%) patients experienced NACE and MACE, respectively. The incidence of NACEs was higher in the PEGASUS-only group (15.4% vs. 8.4%; p = 0.008) and numerically higher in the COMPASS-only group (10.9% vs. 8.4%; p = 0.299).
Conclusions
In a contemporary real-world ACS cohort, approximately two-thirds of patients that complete 1-year DAPT met the eligibility criteria for ticagrelor 60 mg twice daily or rivaroxaban 2.5 mg twice daily, showing a higher risk of NACEs.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 21 Oct 2021; epub ahead of print
Cesaro A, Gragnano F, Calabrò P, Moscarella E, ... Marcucci R, START-ANTIPLATELET collaborators
Int J Cardiol: 21 Oct 2021; epub ahead of print | PMID: 34695525
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Impact:
Abstract

Early diastolic strain rate in relation to long term prognosis following isolated coronary artery bypass grafting.

Lassen MCH, Lindberg S, Olsen FJ, Fritz-Hansen T, ... Møgelvang R, Biering-Sørensen T
Background
The ratio of early mitral inflow velocity to early diastolic strain rate (E/e\'sr) is a novel echocardiographic measure to estimate early left ventricular (LV) filling pressure. We hypothesize that E/e\'sr is a predictor of outcome following coronary artery bypass grafting (CABG) and that it is superior to the conventionally used E/e\'.
Methods & results
Consecutive patients undergoing isolated CABG at Gentofte Hospital (n = 652) were included. The mean age of the study population was 67 ± 9 years, 84% were male, mean LVEF was 50 ± 11%. Prior to surgery, all patients underwent an extensive echocardiographic examination. The outcome was all-cause mortality. During follow-up (median 3.8 years [IQR: 2.7; 4.9 years]), a total of 73 (11%) died. Both E/e\' and E/e\'sr were significant predictors in univariable models. In a multivariable model, E/e\'sr remained an independent predictor of outcome (HR:1.05 [1.01-1.10], p = 0.049, per 10 cm increase) whereas E/e\' did not (HR:1.05 [0.99-1.11], p = 0.053, per 1-unit increase). The relationship between E/e\'sr, and the outcome was significantly modified by GLS (p for interaction = 0.043). In the multivariable model, E/e\'sr was still significantly associated with the outcome in patients with high GLS (≥13.6%) (HR:1.18 [1.02-1.36], p = 0.029) but not in patients with low GLS (HR 1.04 CI95%: [0.99-1.10], p = 0.14). E/e\' was not a significant predictor of all-cause mortality after multivariable adjustment in neither of the groups. E/e\'sr improved net reclassification with 33% when added to EuroSCOREII.
Conclusion
Following CABG, preoperative E/e\'sr is an independent predictor of all-cause mortality, especially in patients with preserved systolic function and superior to E/e\'.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 20 Oct 2021; epub ahead of print
Lassen MCH, Lindberg S, Olsen FJ, Fritz-Hansen T, ... Møgelvang R, Biering-Sørensen T
Int J Cardiol: 20 Oct 2021; epub ahead of print | PMID: 34688721
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Impact:
Abstract

New evidence of direct oral anticoagulation therapy on cardiac valve calcifications, renal preservation and inflammatory modulation.

Di Lullo L, Lavalle C, Magnocavallo M, Mariani MV, ... Natale A, Bellasi A
Background
Rivaroxaban is a direct inhibitor of activated Factor X (FXa), an anti-inflammatory protein exerting a protective effect on the cardiac valve and vascular endothelium. We compare the effect of Warfarin and Rivaroxaban on inflammation biomarkers and their contribution to heart valve calcification progression and renal preservation in a population of atrial fibrillation (AF) patients with chronic kidney disease (CKD) stage 3b - 4.
Methods
This was an observational, multicenter, prospective study enrolling 347 consecutive CKD stage 3b - 4 patients newly diagnosed with AF: 247 were treated with Rivaroxaban and 100 with Warfarin. Every 12 months, we measured creatinine levels and cardiac valve calcification via standard trans-thoracic echocardiogram, while plasma levels of inflammatory mediators were quantified by ELISA at baseline and after 24 months.
Results
Over a follow-up of 24 months, long-term treatment with Rivaroxaban was associated with a significative reduction of cytokines. Patients treated with Rivaroxaban experienced a more frequent stabilization/regression of valve calcifications comparing with patients treated with Warfarin. Rivaroxaban use was related with an improvement in kidney function in 87.4% of patients, while in those treated with Warfarin was reported a worsening of renal clearance in 98% of cases. Patients taking Rivaroxaban experienced lower adverse events (3.2% vs 49%, p-value <0.001).
Conclusions
Our findings suggest that Rivaroxaban compared to Warfarin is associated with lower levels of serum markers of inflammation. The inhibition of FXa may exert an anti-inflammatory effect contributing to reduce the risk of cardiac valve calcification progression and worsening of renal function.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 20 Oct 2021; epub ahead of print
Di Lullo L, Lavalle C, Magnocavallo M, Mariani MV, ... Natale A, Bellasi A
Int J Cardiol: 20 Oct 2021; epub ahead of print | PMID: 34688719
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Impact:
Abstract

Screening for paroxysmal atrial fibrillation in primary care using Holter monitoring and intermittent, ambulatory single-lead electrocardiography.

Karregat EPM, Gurp NV, Bouwman AC, Uittenbogaart SB, ... van Weert HCPM, Stoffers HEJH
Background
Timely detection of atrial fibrillation (AF) is important because of its increased risk of thrombo-embolic events. Single time point screening interventions fall short in detection of paroxysmal AF, which requires prolonged electrocardiographic monitoring, usually using a Holter. However, traditional 24-48 h Holter monitoring is less appropriate for screening purposes because of its low diagnostic yield. Intermittent, ambulatory screening using a single-lead electrocardiogram (1 L-ECG) device can offer a more efficient alternative.
Methods
Primary care patients of ≥65 years participated in an opportunistic screening study for AF. We invited patients with a negative 12 L-ECG to wear a Holter monitor for two weeks and to use a MyDiagnostick 1 L-ECG device thrice daily. We report the yield of paroxysmal AF found by Holter monitoring and calculate the diagnostic accuracy of the 1 L-ECG device\'s built-in AF detection algorithm with the Holter monitor as reference standard.
Results
We included 270 patients, of whom four had AF in a median of 8.0 days of Holter monitoring, a diagnostic yield of 1.5% (95%-CI: 0.4-3.8%). In 205 patients we performed simultaneous 1 L-ECG screening. For diagnosing AF based on the 1 L-ECG device\'s AF detection algorithm, sensitivity was 66.7% (95%-CI: 9.4-99.2%), specificity 68.8% (95%-CI: 61.9-75.1%), positive predictive value 3.1% (95%-CI: 1.4-6.8%) and negative predictive value 99.3% (95%-CI: 96.6-99.9%).
Conclusion
We found a low diagnostic yield of paroxysmal AF using Holter monitoring in elderly primary care patients with a negative 12 L-ECG. The diagnostic accuracy of an intermittently, ambulatory used MyDiagnostick 1 L-ECG device as interpreted by its built-in AF detection algorithm is limited.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 19 Oct 2021; epub ahead of print
Karregat EPM, Gurp NV, Bouwman AC, Uittenbogaart SB, ... van Weert HCPM, Stoffers HEJH
Int J Cardiol: 19 Oct 2021; epub ahead of print | PMID: 34687805
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Impact:
Abstract

LDL cholesterol target achievement in heterozygous familial hypercholesterolemia patients according to 2019 ESC/EAS lipid guidelines: Implications for newer lipid-lowering treatments.

Rizos CV, Skoumas I, Rallidis L, Skalidis E, ... Vlachopoulos C, Liberopoulos EN
Background
The 2019 European guidelines (ESC/EAS) for the treatment of dyslipidaemias recommend more aggressive targets for low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). Current lipid-lowering treatment is often inadequate to achieve these targets.
Methods
Data from the HELLAS-FH registry were analysed to assess achievement of LDL-C targets in adults with FH based on the 2019 ESC/EAS guidelines. In patients who had not achieved LDL-C target, the maximally reduced LDL-C value was calculated after theoretical switch to rosuvastatin/ezetimibe 40/10 mg/day. The percentage of patients who remained candidates for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) was then calculated.
Results
Patients (n = 1694, mean age 50.8 ± 14.7 years) had LDL-C levels 242 ± 71 mg/dL (6.3 ± 1.8 mmol/L) at diagnosis. Most treated patients were receiving statins (97.5%) and about half were on additional ezetimibe (47.5%). Based on the 2019 ESC/EAS guidelines the percentage of patients achieving LDL-C goals was only 2.7%. Following theoretical up titration to rosuvastatin/ezetimibe 40/10 mg, LDL-C target achievement rate would increase to 5.9%. In this scenario, most patients (55.9%) would be eligible for PCSK9i treatment. Following theoretical administration of a PCSK9i, LDL-C target achievement rate would rise to 57.6%. However, 42.4% of patients would still be eligible for further LDL-C lowering treatment.
Conclusions
Most FH patients do not reach new LDL-C targets even if on maximum intensity statin/ezetimibe treatment. In this case, more than half of FH patients are candidates for PCSK9i therapy and a considerable proportion may still require additional LDL-C lowering.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 19 Oct 2021; epub ahead of print
Rizos CV, Skoumas I, Rallidis L, Skalidis E, ... Vlachopoulos C, Liberopoulos EN
Int J Cardiol: 19 Oct 2021; epub ahead of print | PMID: 34687802
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Impact:
Abstract

Subclinical left ventricle impairment following breast cancer radiotherapy: Is there an association between segmental doses and segmental strain dysfunction?

Fourati N, Charfeddine S, Chaffai I, Dhouib F, ... Mnejja W, Daoud J
Background
Cardiotoxicity following breast cancer radiotherapy (RT) represents one of the most redoubtable toxicities. The Global longitudinal strain measurement (GLS) based on 2D speckle tracking imaging (STI) allows detection of left ventricular (LV) dysfunction at a subclinical stage. The aim of this prospective study was to detect patients at risk of cardiotoxicity using echocardiographic parameters and to determine the association between segmental RT doses and early cardiac toxicity.
Material and methods
The STI was performed prior to RT and at 3, 6 and 12 months after. The association between subclinical LV dysfunction, defined as a reduction of GLS more than 10% from the initial value, radiation doses to different LV segments and non-radiation factors were performed based on multivariate analyses.
Results
From June 2017 to August 2018, a total of 103 female patients were included. Sixty patients had left sided RT. Seven patients (7.8%) developed a GSL impairment. The segmental alterations predominated in the anteroseptal and apical LV segments. The mean Dmean in altered segments was significantly higher than in non-altered segments (6.7 ± 8.8Gy-7.8 ± 8.9Gy vs 4.9 ± 7.9-5.4 ± 8.2Gy; p < 0.05). Age > 55 years and obesity were important confounding factors that should be considered during radiotherapy planning.
Conclusion
The results of our study show that radiation dose is correlated with the subclinical LV segments\' alteration. Global heart delineation seems to be insufficient during the breast radiotherapy planning. Segmental delineation of the LV may be an interesting alternative to limit segmental doses and to reduce the risk of subclinical alterations. A mean dose of 5Gy could be proposed in exposed heart segment.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 19 Oct 2021; epub ahead of print
Fourati N, Charfeddine S, Chaffai I, Dhouib F, ... Mnejja W, Daoud J
Int J Cardiol: 19 Oct 2021; epub ahead of print | PMID: 34687800
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Impact:
Abstract

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

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

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

Int J Cardiol: 14 Oct 2021; 341:24-30
Rashid FN, Clayton ZE, Ogawa M, Perdomo J, ... Kizana E, Chong JJH
Int J Cardiol: 14 Oct 2021; 341:24-30 | PMID: 34265313
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Impact:
Abstract

Halving cardiovascular risk with combined blood pressure and cholesterol lowering - Why are we not there yet?

Wang N, Huffman MD, Sundström J, Rodgers A
Background
We aimed to assess whether the modest major adverse cardiovascular events (MACE) reductions in previous trials testing combined blood pressure (BP) and low density lipoprotein cholesterol (LDL-C) reduction were due to modest risk factor reduction and/or a negative interaction, whereby the joint effects of therapy are less than expected.
Methods
We performed a systematic review of randomized controlled trials comparing patients who received combination BP and cholesterol lowering treatment versus placebo. We calculated the expected relative risk reduction (RRR) in MACE based on the observed reductions in systolic BP and LDL-C in each trial and previous meta-analysis of the individual modalities.
Results
All five included trials achieved small SBP reductions (range 1 to 6 mmHg) and small-to-moderate LDL-C reductions (range 0.5 to 1.1 mmol/L), which were all less than expected. Each of the three largest trials achieved significant reductions in MACE and the observed vs expected RRRs were closely aligned: - ASCOT observed RRR 32% (95% CI 18-43%) vs expected RRR 24% (95% CI 20-28%); HOPE-3 observed RRR 28%, (95% CI 10-42%) vs expected RRR 28% (95% CI 23%-31%); TIPS-3 observed RRR 20% (95% CI 0%-36%) vs expected RRR 21% (95% CI 18-24%).
Conclusions
MACE reductions seen in past trials of combined BP and LDL-C reflect the degree of risk factor reduction. Sustained and substantial reductions in BP and LDL-C (eg. ≥15 mmHg and ≥ 1.5 mmol/L) are required to halve cardiovascular risk, which in turn requires long-term adherence to intensive LDL-C lowering and combination BP therapy.

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

Int J Cardiol: 14 Oct 2021; 341:96-99
Wang N, Huffman MD, Sundström J, Rodgers A
Int J Cardiol: 14 Oct 2021; 341:96-99 | PMID: 34411644
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Impact:
Abstract

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

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

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

Int J Cardiol: 14 Oct 2021; 341:1-8
Webb CM, Collins P
Int J Cardiol: 14 Oct 2021; 341:1-8 | PMID: 34273431
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Impact:
Abstract

Long-term prognosis and genetic background of cardiomyopathy in 223 pediatric mitochondrial disease patients.

Imai-Okazaki A, Matsunaga A, Yatsuka Y, Nitta KR, ... Murayama K, Okazaki Y
Background
Cardiomyopathy is a risk factor for poor prognosis in pediatric patients with mitochondrial disease. However, other risk factors including genetic factors related to poor prognosis in mitochondrial disease has yet to be fully elucidated.
Methods and results
Between January 2004 and September 2019, we enrolled 223 consecutive pediatric mitochondrial disease patients aged <18 years with a confirmed genetic diagnosis, including 114 with nuclear gene mutations, 89 patients with mitochondrial DNA (mtDNA) point mutations, 11 with mtDNA single large-scale deletions and 9 with chromosomal aberrations. Cardiomyopathy at baseline was observed in 46 patients (21%). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for all-cause mortality. Over a median follow-up of 36 months (12-77), there were 85 deaths (38%). The overall survival rate was significantly lower in patients with cardiomyopathy than in those without (p < 0.001, log-rank test). By multivariable analysis, left ventricular (LV) hypertrophy (HR = 4.6; 95% CI: 2.8-7.3), neonatal onset (HR = 2.9; 95% CI: 1.8-4.5) and chromosomal aberrations (HR = 2.9; 95% CI: 1.3-6.5) were independent predictors of all-cause mortality. Patients with LV hypertrophy with neonatal onset and/or chromosomal aberrations had higher mortality (100% in 21 patients) than those with LV hypertrophy alone (71% in 14 patients).
Conclusion
In pediatric patients with mitochondrial disease, cardiomyopathy was common (21%) and was associated with increased mortality. LV hypertrophy, neonatal onset and chromosomal aberrations were independent predictors of all-cause mortality. Prognosis is particularly unfavorable if LV hypertrophy is combined with neonatal onset and/or chromosomal aberrations.

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

Int J Cardiol: 14 Oct 2021; 341:48-55
Imai-Okazaki A, Matsunaga A, Yatsuka Y, Nitta KR, ... Murayama K, Okazaki Y
Int J Cardiol: 14 Oct 2021; 341:48-55 | PMID: 34298071
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Impact:
Abstract

Impact of cyanosis on ventilatory responses during stair climb exercise in Eisenmenger syndrome and idiopathic pulmonary arterial hypertension.

Samaranayake CB, Warren C, Siewers K, Craig S, ... Hull JH, McCabe C
Studies assessing exercise ventilatory responses during real-life exercise in pulmonary arterial hypertension (PAH) which include patients with cyanotic congenital heart disease are scarce. We assessed the ventilatory response to stairclimbing in patients with idiopathic PAH (IPAH) and congenital heart disease-associated PAH with Eisenmenger (EIS) physiology compared to healthy controls. Fifteen adults with IPAH, six EIS and 15 age and body mass index (BMI) matched controls were prospectively recruited. Participants completed spirometry and a self-paced stair-climb (48 steps) with portable cardiopulmonary exercise testing (CPET) equipment in-situ. Borg dyspnoea scores were measured at rest and on stair-climb cessation. Both IPAH and EIS groups had amplified ventilatory responses compared to Controls. The rate of increase in minute ventilation (VE) was exaggerated in EIS driven by an early increase in tidal volume (Tv) and more gradual increase in respiratory rate (RR). Peak Tv, RR, Tv: forced vital capacity (FVC) ratio, VE/VCO2 slope and stairclimb duration were significantly higher in EIS and IPAH compared to controls despite similar baseline spirometry and change in oxygen uptake on exercise. A decline in end-tidal carbon dioxide (CO2) and arterial oxygen saturations in early exercise distinguished EIS and IPAH patients. Significant correlations were observed between peak exercise Borg score and stair-climb time (r = 0.73, p = 0.002), peak end-tidal CO2 (r = -0.73, p = 0.001), peak VE (r = 0.53, p = 0.008), peak RR (r = 0.42, p = 0.011) and VE/VCO2 slope (r = 0.54, p = 0.001). Patients with IPAH and EIS have exaggerated ventilatory responses to stair-climbing compared to the controls with more severe levels of dyspnoea perception in Eisenmenger syndrome for equivalent oxygen uptake and work.

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

Int J Cardiol: 14 Oct 2021; 341:84-87
Samaranayake CB, Warren C, Siewers K, Craig S, ... Hull JH, McCabe C
Int J Cardiol: 14 Oct 2021; 341:84-87 | PMID: 34416318
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Impact:
Abstract

Morphologic investigation on Perceval S, a sutureless pericardial valve prosthesis: collagen integrity after collapsing-ballooning and structural valve deterioration at distance.

Bejko J, Della Barbera M, Valente M, Pettenazzo E, ... Basso C, Thiene G
Perceval S is a self-expandable, stent-mounted bioprosthetic valve (BPV), with glutaraldehyde treated bovine pericardium, processed with homocysteic acid as an anti-calcification treatment. The stent is crimpable but the valve insertion is done surgically via a shorter procedure which does not require sutures. OBJECTIVES: MATERIAL AND
Methods:

Results:

Conclusions:
Collapsing and ballooning do not alter cusp collagen periodicity. Structural valve deterioration with stenosis, due to dystrophic calcification and fibrous tissue overgrowth, seldom occurred in the mid-term. Glutaraldehyde fixed pericardium has the potential to undergo structural valve deterioration with time, similar to well-known BPV failure. This supports the recommendation to pursue improvement of tissue valve treatment with enhanced durability.


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

Int J Cardiol: 14 Oct 2021; 341:62-67
Bejko J, Della Barbera M, Valente M, Pettenazzo E, ... Basso C, Thiene G
Int J Cardiol: 14 Oct 2021; 341:62-67 | PMID: 34324948
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Impact:
Abstract

Epigenetic effects following acute and chronic exercise in cardiovascular disease: A systematic review.

Papaioannou F, Karatzanos E, Chatziandreou I, Philippou A, Nanas S, Dimopoulos S
Introduction
Acute exercise and exercise training may confer epigenetic modifications in healthy subjects. Epigenetic effects after exercise have been showed in patients with cardiovascular disease. The aim of this systematic review was to summarize the evidence from available clinical trials that study epigenetic adaptations after exercise in patients with cardiovascular disease.
Methods
The search strategy was performed in PubMed and CENTRAL databases on articles published until September 2020. Studies with titles and abstracts relevant to exercise epigenetic modification applied to cardiovascular patients were fully examined. Inclusion and exclusion criteria were utilized for studies screening. Quality assessment with PEDro scale and evaluation by two independent reviewers was performed.
Results
Of the 1714 articles retrieved, 88 articles were assessed for eligibility criteria and 8 articles matched our search criteria and finally included in the systematic analysis. The acute exercise epigenetic (miRNAs) effects were assessed in three studies and the chronic exercise training effects (miRNAs and DNA methylation) in six studies. The results have shown that there is possibly an acute significant exercise effect on epigenetic targets which is more evident after chronic exercise training.
Conclusions
By the present systematic review, we provide preliminary evidence of beneficial epigenetic adaptations following acute and chronic exercise in patients with cardiovascular disease. More controlled studies are needed to confirm such evidence.

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

Int J Cardiol: 14 Oct 2021; 341:88-95
Papaioannou F, Karatzanos E, Chatziandreou I, Philippou A, Nanas S, Dimopoulos S
Int J Cardiol: 14 Oct 2021; 341:88-95 | PMID: 34339767
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Impact:
Abstract

Impact of cancer diagnosis on causes and outcomes of 5.9 million US patients with cardiovascular admissions.

Matetic A, Mohamed M, Miller RJH, Kolman L, ... Bianco C, Mamas MA
Introduction
There are limited data on causes of cardiovascular (CV) admissions and associated outcomes among patients with different cancers.
Methods
All CV admissions from the US National Inpatient Sample between October 2015 to December 2017 were stratified by cancer type as well as metastatic status. Multivariable logistic regression was performed to determine the adjusted odds ratios (aOR) of in-hospital mortality in different groups.
Results
From 5,936,014 eligible CV admissions, cancer was present in 265,221 (4.5%) hospitalizations. There was significant variation in the admission diagnoses among the different cancers, with hematological malignancies being principally associated with heart failure (HF), lung cancer with atrial fibrillation (AF), and colorectal and prostate cancer with acute myocardial infarction (AMI). Admission with haemorrhagic stroke has the highest associated mortality across cancers (20.0-38.4%). In-hospital mortality was higher in cancer than non-cancer patients across most CV admissions (P < 0.001) with AF having the worst prognosis. Compared to group without any cancer, the greatest aOR of mortality was associated with lung cancer in AMI (aOR 2.32, 95% CI 2.18-2.47), ischemic stroke (aOR 2.21, 95%CI 2.08-2.34), AF (aOR 4.69, 95%CI 4.32-5.10) and HF (aOR 2.07, 95%CI 1.89-2.27).
Conclusions
The most common causes of CV admission to hospital vary in patients with different types of cancer, with AMI being most common in patients with colon cancer, HF in patients with hematological malignancies and AF in patients with lung cancer. Patients with cancer, particularly lung cancer, have greater mortality than non-cancer patients after admissions with a CV cause.

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

Int J Cardiol: 14 Oct 2021; 341:76-83
Matetic A, Mohamed M, Miller RJH, Kolman L, ... Bianco C, Mamas MA
Int J Cardiol: 14 Oct 2021; 341:76-83 | PMID: 34333019
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Abstract

The association between late-phase early recurrence within the blanking period after atrial fibrillation catheter ablation and long-term recurrence: Insights from a large-scale multicenter study.

Onishi N, Kaitani K, Nakagawa Y, Inoue K, ... Shizuta S, EAST-AF Investigators
Background
The relationship between the timing of the first early recurrence and late recurrence after a single catheter ablation procedure for atrial fibrillation is controversial.
Methods
The Efficacy of Short-Term Use of Antiarrhythmic Drugs After Catheter Ablation for Atrial Fibrillation trial followed 2038 patients who underwent radiofrequency catheter ablation for atrial fibrillation.
Results
Of the patients, 907 (45%) had early recurrences within 90 days after the initial ablation. We divided these patients into two groups according to the timing of the first early recurrence episode, namely the ER1 group (early recurrence during the early phase; 0-30 days, n = 814) and ER2 group (early recurrence during the late phase; 31-90 days, n = 93). Three years after ablation, patients with early recurrences had a significantly lower event-free rate from late recurrences after a 90-day blanking period than patients without early recurrences (36.2% and 74.2%, respectively; log-rank, P < 0.0001). Three years after ablation, the event-free rate was significantly higher in the ER1 than the ER2 group (38.3% and 17.1%, respectively; log-rank, P < 0.0001). Moreover, the event-free rate at 3 years in the ER2 group was extremely low (5.6%) in patient with non-paroxysmal atrial fibrillation.
Conclusion
Early recurrences were strongly associated with late recurrences, especially in patients with the first recurrence episode at >1 month within the blanking period after a single ablation procedure. Therefore, these patients should undergo close observation during follow-up, when they had especially with non-paroxysmal atrial fibrillation.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 Oct 2021; 341:39-45
Onishi N, Kaitani K, Nakagawa Y, Inoue K, ... Shizuta S, EAST-AF Investigators
Int J Cardiol: 14 Oct 2021; 341:39-45 | PMID: 34343532
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Abstract

Impact of major infections on 10-year mortality after revascularization in patients with complex coronary artery disease.

Ono M, Kawashima H, Hara H, Mancone M, ... Serruys PW, SYNTAX Extended Survival Investigators
Background
The significant interaction between major infection and 5-year mortality after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) for complex coronary artery disease (CAD) was observed previously. However, the very long-term outcomes beyond 5 years remains unclear.
Methods and results
This is a subgroup analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the randomized SYNTAX trial comparing PCI versus CABG in patients with three-vessel disease (3VD) or left-main CAD (LMCAD). Out of 1517 patients enrolled in the SYNTAX trial with available survival status from 5 to 10 years, 140 patients had experienced major infections and survived at 5 years (major infection group). From 5 to 10 years, the mortality of major infection group was 19.8% whereas the mortality of no major infection group was 15.1% (p = 0.157). After the adjustment of other clinical factors, the risk of mortality from 5 to 10 years did not significantly differ between major infection and no major infection groups (HR: 1.10; 95% CI: 0.62-1.96; p = 0.740). When stratified by the presence or absence of periprocedural major infections, defined as a major infection within 60 days after index procedure, there was also no significant difference in 10-year mortality between two groups (30.8% vs. 24.5%; p = 0.057).
Conclusions
Despite the initial association between major infections and 5 years mortality, postprocedural major infection was not evident in the 10 years follow-up, suggesting that the impact of major infection on mortality subsided over time beyond 5 years.
Trial registration
SYNTAXES ClinicalTrials.gov reference: NCT03417050 SYNTAX ClinicalTrials.gov reference: NCT00114972.

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

Int J Cardiol: 14 Oct 2021; 341:9-12
Ono M, Kawashima H, Hara H, Mancone M, ... Serruys PW, SYNTAX Extended Survival Investigators
Int J Cardiol: 14 Oct 2021; 341:9-12 | PMID: 34375706
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Abstract

Determinants of exercise limitation in contemporary paediatric Fontan patients with an extra cardiac conduit.

Harteveld LM, Blom NA, Terol Espinosa de Los Monteros C, van Dijk JG, ... Hazekamp MG, Ten Harkel ADJ
Background
Although various determinants of exercise limitation in Fontan patients have been studied, most research has been performed in patients who underwent different surgical procedures with differing haemodynamic characteristics. The aim of the current study was to evaluate non-invasively measured cardiovascular parameters and their influence on exercise performance in paediatric Fontan patients with an extracardiac conduit and moderate-good systolic ventricular function.
Methods
Fontan patients, between 8 and 18 years of age, with moderate to good systolic ventricular function and an extracardiac conduit were included. Exercise performance and cardiovascular assessment, comprising echocardiography, aortic stiffness measurement and ambulatory measurement of cardiac autonomous nervous activity were performed on the same day. Healthy subjects served as controls.
Results
Thirty-six Fontan patients (age 14.0 years) and thirty-five healthy subjects (age 12.8 years) were included. Compared to controls, Fontan patients had reduced diastolic ventricular function and increased arterial stiffness. No differences were found in heart rate (HR) and cardiac parasympathetic nervous activity. In Fontan patients, maximal as well as submaximal exercise capacity was impaired, with the percentage of predicted capacity ranging between 54 and 72%. Chronotropic competence, however, was good with a peak HR of 174 (94% of predicted). Lower maximal and submaximal exercise capacity was correlated with a higher HR at rest, higher pulse wave velocity of the aorta and a lower ratio of early and late diastolic flow velocity.
Conclusion
Contemporary paediatric Fontan patients have an impaired exercise capacity with preserved chronotropic competence. Exercise performance correlates with heart rate at rest, diastolic function and aortic stiffness.

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

Int J Cardiol: 14 Oct 2021; 341:31-38
Harteveld LM, Blom NA, Terol Espinosa de Los Monteros C, van Dijk JG, ... Hazekamp MG, Ten Harkel ADJ
Int J Cardiol: 14 Oct 2021; 341:31-38 | PMID: 34375703
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Abstract

Single troponin measurement to rule-out acute myocardial infarction in early presenters.

Andersen CF, Bang C, Lauridsen KG, Frederiksen CA, ... Hornung N, Løfgren B
Background
A single high-sensitive cardiac troponin (hs-cTn) can be used to rule-out acute myocardial infarction (MI) in patients presenting >3 hours (3 h) after chest pain onset to the emergency department. This study aimed to investigate the safety of ruling-out MI in early presenters with chest pain ≤3 h using a single hs-cTnI at admission.
Methods
We prospectively enrolled patients presenting with chest pain suggestive of MI. Hs-cTnI (Siemens ADVIA Centaur TNIH, Limit of detection: 2.2 ng/L) was measured at admission. Two physicians adjudicated final diagnosis. A diagnostic cut-off value <3 ng/L was used to rule-out MI. Patients were classified as early (chest pain ≤3 h) or late presenters (>3 h).
Results
We included 1370 patients with available admission hs-cTnI results: median (Q1-Q3) age 65 (52-74), female sex: 43%, previous MI: 22%. We confirmed MI in 118 (8.6%) patients. Overall, 470 (34%) patients were classified as early, 770 (56%) as late presenters, and 130 (9%) patients had unknown onset. When applying the diagnostic cut-off value, MI was correctly ruled-out at admission in 370 (27%) patients: 134 (29%) early presenters, 206 (27%) late presenters and 30 (23%) patients with unknown onset. This resulted in an overall negative predictive value of 100% (95% CI: 99.0-100%), with both 100% (97.3-100%) for early and 100% (98.2-100%) for late presenters, respectively. Sensitivity was similarly high in the two groups.
Conclusion
MI could be safely ruled-out in all patients presenting with chest pain ≤3 h when using a single hs-cTnI value <3 ng/L as diagnostic cut-off.
Trial registration number
NCT03634384.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 Oct 2021; 341:15-21
Andersen CF, Bang C, Lauridsen KG, Frederiksen CA, ... Hornung N, Løfgren B
Int J Cardiol: 14 Oct 2021; 341:15-21 | PMID: 34391791
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Abstract

Thiamine increases resident endoglin positive cardiac progenitor cells and atrial contractile force in humans: A randomised controlled trial.

Coffey S, Dixit P, Saw EL, Babakr AA, ... Katare R, Williams MJA
Background
The heart has an intrinsic ability to regenerate, orchestrated by progenitor or stem cells. However, the relative complexity of non-resident cardiac progenitor cell (CPC) therapy makes modulation of resident CPCs a more attractive treatment target. Thiamine analogues improve resident CPC function in pre-clinical models. In this double blinded randomised controlled trial (identifier: ACTRN12614000755639), we examined whether thiamine would improve CPC function in humans.
Methods and results
High dose oral thiamine (one gram twice daily) or matching placebo was administered 3-5 days prior to coronary artery bypass surgery (CABG). Right atrial appendages were collected at the time of CABG, and CPCs isolated. There was no difference in the primary outcome (proliferation ability of CPCs) between treatment groups. Older age was not associated with decreased proliferation ability. In exploratory analyses, isolated CPCs in the thiamine group showed an increase in the proportion of CD34-/CD105+ (endoglin) cells, but no difference in CD34-/CD90+ or CD34+ cells. Thiamine increased maximum force developed by isolated trabeculae, with no difference in relaxation time or beta-adrenergic responsiveness.
Conclusion
Thiamine does not improve proliferation ability of CPC in patients undergoing CABG, but increases the proportion of CD34-/CD105+ cells. Having not met its primary endpoint, this study provides the impetus to re-examine CPC biology prior to any clinical outcome-based trial examining potential beneficial cardiovascular effects of thiamine.

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

Int J Cardiol: 14 Oct 2021; 341:70-73
Coffey S, Dixit P, Saw EL, Babakr AA, ... Katare R, Williams MJA
Int J Cardiol: 14 Oct 2021; 341:70-73 | PMID: 34461161
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Abstract

Sodium-glucose co-transporter-2 inhibitors eligibility in patients with heart failure with reduced ejection fraction.

Monzo L, Ferrari I, Cicogna F, Tota C, Calò L
Background
The sodium-glucose co-transporter-2 (SGLT2) inhibitors dapagliflozin and empagliflozin have been demonstrated to reduce adverse cardiovascular outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Limited data are available characterizing the generalizability of SGLT2 inhibitors treatment in the clinical practice. The aim of the study was to evaluate the proportion of outpatients with HFrEF that would be eligible for SGLT2 inhibitors in a contemporary real-world population.
Methods
We retrospectively evaluated patients with chronic stable HFrEF followed-up at the HF outpatient clinic of our institution. Patients\' eligibility was assessed according to the entry criteria of DAPA-HF (dapagliflozin) and EMPEROR-Reduced (empagliflozin) trials and to US Food and Drug Administration (FDA) label criteria (only dapagliflozin).
Results
A total of 441 HFrEF patients was enrolled. According to the major inclusion and exclusion criteria from DAPA-HF and EMPEROR-Reduced trials, 198 (45%) patients would be candidates for initiation of both dapagliflozin and empagliflozin, 61 (14%) would be eligible only to dapagliflozin and 23 (5%) only to empagliflozin, without significant differences between diabetic and non-diabetic patients (p = 0.23). Among patients not suitable for gliflozins treatment (159 patients; 36%), the major determinant of ineligibility was the failure to achieve the predefined NT-proBNP inclusion threshold. Excluding NTproBNP as per FDA label criteria, dapagliflozin eligibility increased to 86%.
Conclusions
In our real-world analysis a large proportion of HFrEF patients would be candidates for initiation of SGLT2 inhibitors, supporting its broad generalizability in clinical practice. This would be expected to reduce morbidity and mortality in eligible patients.

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

Int J Cardiol: 14 Oct 2021; 341:56-59
Monzo L, Ferrari I, Cicogna F, Tota C, Calò L
Int J Cardiol: 14 Oct 2021; 341:56-59 | PMID: 34454968
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Abstract

Sport practice in hypertrophic cardiomyopathy: Running to stand still?

Mascia G, Olivotto I, Brugada J, Arbelo E, ... Canepa M, Porto I
During the last decades, the practice of sport and hypertrophic cardiomyopathy (HCM) have been considered as incompatible entities, since the quality of evidence was not sufficient to determine the risk associated to repeat and/or vigorous exercise across the spectrum of HCM. Risk stratification tools developed for HCM subjects have not been derived from athlete cohorts, so that evaluation of HCM subjects for sport eligibility is very challenging in the modern era of shared decision-making. Epidemiological studies that focused on the contribution of HCM as cause of sudden death both in the general population and in athletes, however, are recently supporting the possibility of allowing the practice of some professional sports for certain low-risk HCM categories. We hereby review the pathophysiologic pathways and the complex interaction of vigorous and continuative exercise practice with HCM, critically revising the available evidence relevant to sports eligibility in HCM, the challenge/limitations of shared decision-making, and the potential harms and benefits of sports disqualification in athletes diagnosed with this complex disease.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 Oct 2021; epub ahead of print
Mascia G, Olivotto I, Brugada J, Arbelo E, ... Canepa M, Porto I
Int J Cardiol: 14 Oct 2021; epub ahead of print | PMID: 34662670
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Impact:
Abstract

1,25-dihydroxyvitamin D and cardiometabolic risk in healthy sedentary adults: The FIT-AGEING study.

De-la-O A, Jurado-Fasoli L, Lavie CJ, Castillo MJ, Gutiérrez Á, Amaro-Gahete FJ
Background
A growing body of scientific works investigating the physio-pathological mechanisms behind cardiovascular disease has suggested that vitamin D deficiency could play a key role on its development. However, it remains unclear whether its active form (1,25-dihydroxyvitamin D [1,25(OH)2D] is associated with cardiometabolic risk factors in healthy individuals. The aim of the present study was to investigate the relationships of 1,25(OH)2D plasma levels with cardiometabolic risk factors in a sample of healthy sedentary adults.
Methods
A total of 73 adults (~53% women; 54 ± 5 years old) were included in the current cross-sectional study. A sex-specific cardiometabolic risk score (MetScore) was calculated for each subject based on clinical parameters (i.e., waist circumference, systolic and diastolic blood pressure, plasma glucose, high-density lipoprotein cholesterol, and triglycerides) according to the International Diabetes Federation\'s clinical criteria. Plasma levels of 1,25(OH)2D were measured using a DiaSorin Liaison® immunochemiluminometric analyzer.
Results
No significant association was detected between 1,25(OH)2D and MetScore (β = 0.037, R2 = 0.001, p = 0.77), independently of age, sex and fat body mass index. A significant inverse association were observed between 1,25(OH)2D and waist circumference (β = -0,303, R2 = 0.092, p = 0.01). These results were consistent after controlling by potential confounders.
Conclusion
In summary, the present results suggest that 1,25(OH)2D plasma levels are not associated with either cardiometabolic risk factors or insulin resistance in healthy sedentary adults. However, an inverse association of 1,25(OH)2D plasma levels with central adiposity was observed in our study sample.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 13 Oct 2021; epub ahead of print
De-la-O A, Jurado-Fasoli L, Lavie CJ, Castillo MJ, Gutiérrez Á, Amaro-Gahete FJ
Int J Cardiol: 13 Oct 2021; epub ahead of print | PMID: 34656647
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Impact:
Abstract

Sino-tubular junction to sinuses of Valsalva ratio: An echocardiographic parameter to predict coronary artery ectasia in patients with aortic enlargement.

Ghetti G, Minnucci M, Chietera F, Donati F, ... Galié N, Taglieri N
Background
Coronary artery ectasia (CAE) is associated with ascending aortic (AA) ectasia. The purpose of this study is to evaluate the diagnostic performance of different echocardiographic parameters (EP) in predicting the presence of CAE.
Methods
Four hundred-eighteen patients with AA ectasia candidate to coronary angiography were identified and divided in two groups in respect of the presence of CAE. Receiver-operating characteristic curves areas (AUC) were used to assess the discrimination power of the following EP: aortic annulus diameter, sinuses of Valsalva (SV) diameter, sino-tubular junction (STJ) diameter, AA diameter, STJ to SV ratio (STJ-to-SV) and STJ to AA ratio (STJ-to-AA). All these parameters were indexed by body surface area. The relationship between the best EP and the presence of CAE was investigated by means of multivariable logistic regression.
Results
The rate of CAE in the study population was 32%. On univariable logistic regression, aortic annulus, STJ, STJ-to-SV and STJ-to-AA were associated with the presence of CAE after Bonferroni correction. STJ-to-SV emerged as the parameter with the best discrimination power (AUC = 0.81) compared to STJ (AUC = 0.69), STJ-to-AA (AUC = 0.68), aortic annulus (AUC = 0.59), AA (AUC = 0.56) and SV (AUC = 0.55); (p for comparison <0.01). An 89.6% value for STJ-to-SV ratio emerged as the best cut-off to diagnose CAE with a sensitivity = 75%, specificity = 82%, positive predictive value = 66% and negative predictive value = 88%. On multivariable analysis, STJ-to-SV was still associated with the presence of CAE (OR = 1.15;95%CI:1.11-1.19;p < 0.01).
Conclusion
In patients with dilated aorta, STJ-to-SV sampled by transthoracic echocardiography shows a good diagnostic performance in predicting the presence of CAE.

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

Int J Cardiol: 12 Oct 2021; epub ahead of print
Ghetti G, Minnucci M, Chietera F, Donati F, ... Galié N, Taglieri N
Int J Cardiol: 12 Oct 2021; epub ahead of print | PMID: 34655674
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Impact:
Abstract

Effects of SGLT-2 inhibitors on health-related quality of life and exercise capacity in heart failure patients with reduced ejection fraction: A systematic review and meta-analysis.

He Z, Yang L, Nie Y, Wang Y, ... Yao Y, Zhang Z
Objective
Improving health-related quality of life (HRQoL) and exercise capacity is an important goal of treatment in heart failure (HF). However, evidence for the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on the improvement of HRQoL and exercise capacity seems to be conflicted. We performed a systematic review and meta-analysis to evaluate the effects of SGLT-2 inhibitors on HRQL and exercise capacity in patients with heart failure and reduced ejection fraction (HFrEF).
Methods
All studies (up to March 20, 2021) evaluating the effects of SGLT-2 inhibitors on HRQoL and exercise capacity in patients with HFrEF were initially searched from four electronic search engines: PubMed, Web of Science, Cochrane Library, and SinoMed. All statistical analyses were performed with RevMan 5.4.
Results
We included 9 articles describing 7 trials with 9428 patients. SGLT-2 inhibitors group exhibited significant improvement in HRQoL assessed by Kansas City Cardiomyopathy Questionnaires (KCCQ) (MD: 2.13, 95% CI: 1.11 to 3.14, p < 0.001) and the rate of KCCQ-overall summary score improvement≥5 points (RR 1.15, 95%CI 1.08 to 1.21, P < 0.001) compared with placebo. No significant difference was observed in exercise capacity assessed by 6-min walk test distance between SGLT-2 inhibitors and placebo (MD 24.45, 95%CI -22.82 to 71.72, P = 0.31).
Conclusions
Our meta-analysis demonstrates that SGLT-2 inhibitors significantly improve HRQoL, and supports the concept that SGLT-2 inhibitors do not significantly improve exercise capacity in patients with HFrEF. Studies with larger sample sizes and longer follow-up duration are needed to determine whether the treatment with SGLT-2 inhibitors may improve exercise ability.
Prospero
CRD42021248346.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 11 Oct 2021; epub ahead of print
He Z, Yang L, Nie Y, Wang Y, ... Yao Y, Zhang Z
Int J Cardiol: 11 Oct 2021; epub ahead of print | PMID: 34653575
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Impact:
Abstract

Cardiovascular complications associated with novel agents in the chronic lymphocytic leukemia armamentarium: A pharmacovigilance analysis.

Grewal US, Thotamgari SR, Sheth AR, Gaddam SJ, ... Beedupalli K, Dominic P
Introduction
Over the last few years, improved outcomes in patients with chronic lymphocytic leukemia (CLL) have been credited to the introduction of novel agents for its treatment. However, the overall cardiovascular safety profile of these agents has not been studied adequately.
Methods
We searched the Food and Drug Administration Adverse Event Reporting System (FAERS) database for adverse events reported for several of these novel agents: ibrutinib, acalabrutinib, venetoclax, and idelalisib.
Results
A total of 6074 cardiac adverse events were identified; ibrutinib (4832/36581; 13.2%) was found to have the highest risk of cardiac adverse events. The frequency of atrial fibrillation was highest (41.5%) in the ibrutinib group, while the idelalisib and acalabrutinib groups had the highest reported frequencies of heart failure (25.1%) and myocardial infarction (13.6%), respectively. Hypertension was noted to be relatively higher in the acalabrutinib (25.6%) and venetoclax (11.8%) groups. Overall reported mortality associated with cardiac events was highest in the venetoclax (29.4%) and idelalisib (27.1%) groups.
Conclusion
Novel agents in the CLL armamentarium have been associated with several cardiovascular adverse events. Further studies are needed to identify high-risk groups that would benefit from robust cardiovascular surveillance after initiation of treatment with these novel agents.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 11 Oct 2021; epub ahead of print
Grewal US, Thotamgari SR, Sheth AR, Gaddam SJ, ... Beedupalli K, Dominic P
Int J Cardiol: 11 Oct 2021; epub ahead of print | PMID: 34653574
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Impact:
Abstract

Prevalence and prognosis of pericardial effusion in patients affected by pectus excavatum: A case-control study.

Conte E, Agalbato C, Lauri G, Mushtaq S, ... Andreini D, Brucato A
Background
The presence of pectus excavatum(PEX) has been occasionally associated with pericardial effusion. Aim of the present study was to compare incidence and prognosis of pericardial effusion in a group of unselected patients with PEX vs a control group.
Methods
From a prospective registry of consecutive patients who underwent chest CT for cardiovascular disease, subjects with a radiological diagnosis of PEX were retrospectively identified (cases); from the same registry patients (controls) without rib cage abnormalities were randomly selected, until a 1:2 ratio was reached. The presence of pericardial effusion at CT was quantified. Follow-up was obtained for a composite end-point: cardiac tamponade, need for pericardiocentesis, need for cardiac surgery for relapsing pericardial effusion.
Results
A total of 43 patients with PEX (20 females) and a control group of 86 cases (31 females) without rib cage abnormalities were identified. Pericardial effusion evaluated at CT was significatively more prevalent in patients with PEX vs control group, 37.2% vs 13.9% (p < 0.001), respectively; four patients with PEX (9.3%) had at least moderate pericardial effusion vs no subjects among the controls (p = 0.004). PEX diagnosis was significantly associated to pericardial effusion at multi-variate analysis (OR95%CI 10.91[3.47-34.29], p < 0.001). At a mean follow-up of 6.5 ± 3.4 years no pericardial events were recorded.
Conclusion
Our findings support the higher prevalence of pericardial effusion in patients with PEX when compared to a control group. The absence of adverse pericardial events at follow-up suggest the good prognosis of these effusions, that in the appropriate clinical setting might not be considered \"idiopathic\".

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

Int J Cardiol: 06 Oct 2021; epub ahead of print
Conte E, Agalbato C, Lauri G, Mushtaq S, ... Andreini D, Brucato A
Int J Cardiol: 06 Oct 2021; epub ahead of print | PMID: 34626741
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Impact:
Abstract

Real-world experience of feasibility and efficacy of electrical muscle stimulation in elderly patients with acute heart failure: A randomized controlled study.

Arenja N, Mueller C, Tomilovskaya E, Koryak Y, Poltavskaya M, Saner H
Background
Reduced aerobic capacity and deconditioning contributes to morbidity and mortality in elderly acute heart failure (AHF) patients. Electrical muscle stimulation (EMS) has shown to be a suitable alternative to exercise in AHF. However, feasibility and efficacy are unknown in a real-world setting.
Methods
This is a prospective, open label blinded, randomized, controlled study, investigating feasibility and efficacy of high-intensity versus low-intensity EMS versus controls in elderly AHF patients. Patients and investigators were blinded to the intervention. EMS was offered to >60 years old AHF patients, initiated during hospitalization and continued at home. Outcome measures included changes in 6-min walk distance (6-MWTD), functional capacity and quality-of-life at 3 and 6 weeks.
Results
Among 97 consecutive AHF patients (78.1 ± 9.4 years, 42.3% females), 60 (61.9%) were eligible for EMS. Of these, 27 provided written informed consent and were randomly assigned to high-intensity (n = 10), low-intensity EMS (n = 9) and controls (n = 8). 13/27 completed the intervention. Main reason for dropouts was intolerance of the overall intervention burden. MACE occurred in 5 and were not associated with the study. EMS groups showed significant improvement of 6-MWTD (controls vs low-intensity p = 0.018) and of independence in daily living (for both p < 0.05).
Conclusions
Changes in 6-MWDT suggest efficacy of EMS. Whereas all tolerated EMS well, the burden of study intervention was too high and resulted in a consent rate of <50% and high dropouts, which limit the interpretability of our data. Less demanding EMS protocols are required to evaluate the full potential of EMS in elderly AHF patients.

Copyright © 2021 Elsevier Ireland Ltd. All rights reserved.

Int J Cardiol: 06 Oct 2021; epub ahead of print
Arenja N, Mueller C, Tomilovskaya E, Koryak Y, Poltavskaya M, Saner H
Int J Cardiol: 06 Oct 2021; epub ahead of print | PMID: 34627967
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Impact:
Abstract

Outcomes of distal versus conventional transradial access for coronary angiography and intervention: An updated systematic review and meta-analysis.

Mhanna M, Beran A, Nazir S, Al-Abdouh A, ... Malhas SE, Eltahawy EA
Introduction
Distal transradial artery access (DTRA) has recently gained attention due to potential benefits in terms of local complications. In this meta-analysis, we aimed to evaluate the utility of DTRA compared to conventional transradial artery access (CTRA) for coronary angiography and intervention.
Method
Multiple databases were searched from inception through May 2021 for all the studies that evaluated the efficacy and safety of DTRA in the coronary field. The primary outcome was the access success rate. The secondary outcomes were periprocedural local complications (site hematoma, radial artery occlusion, and spasm) and procedural characteristics (cannulation, fluoroscopy, procedure, and radial artery compression times). All meta-analyses were conducted using a random-effect model.
Results
A total of 12 studies (including four randomized control trials) with 1634 patients who underwent DTRA vs. 1657 with CTRA were included in the final analysis. The access success rate was similar between the two groups (odds ratio (OR):0.62; 95% confidence interval (CI):0.30-1.26; P = 0.18; I2 = 61%). DTRA was associated with a statistically significant lower rate of radial artery occlusion (OR:0.36; 95% CI: 0.22-0.59; P < 0.001; I2 = 0%) but similar rates of radial artery spasm and site hematoma when compared to CTRA. Regarding the procedural characteristics, despite having a longer canulation time (mean difference (min.) [MD] 0.89, 95% CI 0.36-1.42; P < 0.0001), DTRA was associated with shorter compression time and comparable fluoroscopy and procedure times.
Conclusions
Our meta-analysis demonstrates that the DTRA is effective and safe with superiority in preventing radial artery occlusion when compared to CTRA.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 05 Oct 2021; epub ahead of print
Mhanna M, Beran A, Nazir S, Al-Abdouh A, ... Malhas SE, Eltahawy EA
Int J Cardiol: 05 Oct 2021; epub ahead of print | PMID: 34626744
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Impact:
Abstract

Loss of left ventricular rotation is a significant determinant of functional mitral regurgitation.

Hasin T, Mann D, Welt M, Barrett O, ... Glikson M, Wolak A
Aim
To evaluate insufficient rotational movement of the left ventricle (LV) as a potential novel mechanism for functional regurgitation of the mitral valve (FMR).
Methods and results
We compared reference subjects and patients with LV dysfunction (LVD, ejection fraction EF < 50%) with and without FMR (regurgitant volume RVol>10 mL). Subjects without structural mitral valve pathology undergoing cardiac MRI were evaluated. Delayed enhancement, global LV remodeling parameters, systolic twist and torsion were measured (using manual and novel automated cardiac MRI tissue-tracking). The study included 117 subjects with mean ± SD age 50.4 ± 17.8 years, of which 30.8% were female. Compared to subjects with LVD without FMR (n = 31), those with FMR (n = 37) had similar clinical characteristics, diagnoses, delayed enhancement, EF, and longitudinal strain. Subjects with FMR had significantly larger left ventricles (EDVi:136.6 ± 41.8 vs 97.5 ± 26.2 mL/m, p < 0.0001) with wider separation between papillary muscles (21.1 ± 7.6 vs 17.2 ± 5.7 mm, p = 0.023). Notably, they had lower apical (p < 0.0001) but not basal rotation and lower peak systolic twist (3.1 ± 2.4° vs 5.5 ± 2.5°, p < 0.0001) and torsion (0.56 ± 0.38°/cm vs 0.88 ± 0.52°/cm, p = 0.004). In a multivariate model for RVol including age, gender, twist, LV end-diastolic volume, sphericity index and separation between papillary muscles, only gender, volume and twist were significant. Twist was the most powerful correlate (beta -2.23, CI -3.26 to -1.23 p < 0.001). In patients with FMR, peak systolic twist negatively correlates with RVol (r = -0.73, p < 0.0001).
Conclusion
Reduced rotational systolic LV motion is significantly and independently associated with RVol among patients with FMR, suggesting a novel pathophysiological mechanism and a potential therapeutic target.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 05 Oct 2021; epub ahead of print
Hasin T, Mann D, Welt M, Barrett O, ... Glikson M, Wolak A
Int J Cardiol: 05 Oct 2021; epub ahead of print | PMID: 34626742
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Abstract

Ticagrelor versus prasugrel in patients with acute myocardial infarction.

Park S, Kim YG, Ann SH, Park HW, ... Han S, Park GM
Background
Ticagrelor and prasugrel are the mainstay of antithrombotic therapy for patients with acute myocardial infarction (MI). However, direct comparative data on clinical outcomes of potent P2Y12 inhibitors are limited, especially in East Asian populations. We aimed to evaluate the effect of ticagrelor versus prasugrel on clinical outcomes in patients with acute MI.
Methods
From the Korean nationwide National Health Insurance database, 10,797 patients with acute MI who received either ticagrelor or prasugrel in combination with aspirin after percutaneous coronary intervention (PCI) were enrolled. The primary outcome was net clinical benefit, defined as a composite of death, MI, stroke, or major bleeding. Secondary outcomes included the individual components of the primary outcome as effectiveness and safety measures.
Results
Among 10,797 patients, 9591 (88.8%) received ticagrelor and 1206 (11.2%) received prasugrel. During a median follow-up of 1.8 years, the primary outcome occurred in 1051 (16.6%) and 131 (14.4%) patients in the ticagrelor and prasugrel groups, respectively. In the propensity score matched cohort (n = 5979), the risk for the primary outcome was similar between the two groups (hazard ratio [HR] 0.949 for prasugrel; 95% confidence interval [CI]: 0.780-1.154). The risks for the composite of death, MI, or stroke (HR 0.938; 95% CI: 0.752-1.169) and major bleeding (HR 1.022; 95% CI: 0.709-1.472) were also comparable.
Conclusions
In patients with acute MI undergoing PCI, ticagrelor and prasugrel appeared to have similar net clinical benefits. The risks for death, MI, or stroke and major bleeding were not significantly different between the two groups.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 03 Oct 2021; epub ahead of print
Park S, Kim YG, Ann SH, Park HW, ... Han S, Park GM
Int J Cardiol: 03 Oct 2021; epub ahead of print | PMID: 34619265
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Abstract

Reversible increase in stress-associated neurobiological activity in the acute phase of Takotsubo syndrome; a brain F-FDG-PET study.

Suzuki H, Takanami K, Takase K, Shimokawa H, Yasuda S
Introduction
Takotsubo syndrome (TTS) is triggered mostly by physical and/or emotional stress that is processed in stress-associated brain regions, including the amygdala. However, it remains unclear whether such stress-induced brain activity is associated with TTS onset.
Methods and results
We acquired brain [18F]-2-fluoro-deoxy-d-glucose (18F-FDG) positron emission tomography in 4 TTS patients (44-82 yrs., 3 women) on days 2-4 (acute phase) and days 29-40 (recovery phase) after diagnosis of TTS was made by coronary angiography and left ventriculogram. The 18F-FDG uptake was measured globally and also in the pre-defined regions of interest of the bilateral amygdala on the common Montreal Neurological Institute space; all 18F-FDG images were normalized using automated image pre-processing. Amygdalar activity was calculated by dividing the 18F-FDG uptake of the amygdala by the global brain uptake. Left ventriculograms showed that apical ballooning was typical at diagnosis and was then relieved in the recovery phase. Amygdalar activity in the acute phase (0.872 ± 0.032) was higher than in the recovery phase (0.805 ± 0.037) (P = 0.013).
Conclusions
We report here 4 cases of TTS showing higher amygdalar activity in the acute phase as compared with the recovery phase, suggesting that increased stress-induced neurobiological activity is associated with TTS onset.

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

Int J Cardiol: 03 Oct 2021; epub ahead of print
Suzuki H, Takanami K, Takase K, Shimokawa H, Yasuda S
Int J Cardiol: 03 Oct 2021; epub ahead of print | PMID: 34619263
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Abstract

Pre-admission acetylsalicylic acid therapy and impact on in-hospital outcome in COVID-19 patients: The ASA-CARE study.

Sisinni A, Rossi L, Battista A, Poletti E, ... Guazzi M, Godino C
Background
Patients with coronavirus disease 2019 (COVID-19) exhibit high thrombotic risk. The evidence on a potential independent prognostic role of antiplatelet treatment in those patients is limited. The aim of the study was to evaluate the prognostic impact of pre-admission low-dose acetylsalicylic acid (ASA) in a wide series of hospitalized patients with COVID-19.
Methods
This cohort study included 984 COVID-19 patients stratified according to ASA intake before hospitalization: ASA+ (n = 253) and ASA- (n = 731). Patients were included in ASA+ group if they received it daily in the 7 days before admission. 213 (83%) were on ASA 100 mg daily. Primary endpoint was a composite of in-hospital death and/or need for respiratory support upgrade, secondary endpoints were in-hospital death and need for respiratory support upgrade.
Results
Mean age was 72 [62; 81] with 69% of male patients. ASA+ patients were significantly older, with higher prevalence of comorbidities. No significant differences regarding the degree of respiratory dysfunction were observed. At 30-day Kaplan-Meier analysis, ASA+ patients had higher survival free from the primary endpoint and need for respiratory support upgrade, conversely in-hospital death did not significantly differ between groups. At multivariate analysis ASA intake was independently associated with a lower probability of reaching primary endpoint (HR 0.697, 95% C.I. 0.525-0.924; p = 0.012).
Conclusions
In COVID-19 patients undergoing hospitalization, pre-admission treatment with ASA is associated with better in-hospital outcome, mainly driven by less respiratory support upgrade.

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

Int J Cardiol: 03 Oct 2021; epub ahead of print
Sisinni A, Rossi L, Battista A, Poletti E, ... Guazzi M, Godino C
Int J Cardiol: 03 Oct 2021; epub ahead of print | PMID: 34619262
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Impact:
Abstract

Clinical and echocardiographic outcomes of transcatheter mitral valve repair in atrial functional mitral regurgitation.

Benito-González T, Carrasco-Chinchilla F, Estévez-Loureiro R, Pascual I, ... Alonso-Briales JH, Fernández-Vázquez F
Background
Isolated atrial fibrillation can cause mitral regurgitation (MR) in patients with normal left ventricular systolic function and no organic disease of the mitral valve. Little information is available regarding outcomes of Mitraclip in patients with atrial functional mitral regurgitation (AFMR). We aimed to evaluate 12-month clinical and echocardiographic outcomes of transcatheter mitral valve repair (TMVR) with MitraClip in patients with AFMR compared to those with ventricular functional or degenerative/mixed MR.
Methods
Registry-based analysis of all consecutive patients who underwent TMVR and were included in the Spanish Registry of Mitraclip. Changes in MR and NYHA functional class, and a combined endpoint including all-cause mortality and hospitalizations due to heart failure were the main outcomes.
Results
Overall, 1074 (69.1% male, 73.3 ± 10.2 years-old) patients were analyzed in this report. 48 patients (4.5%) presented AFMR. AFMR was significantly reduced after TMVR, with a procedural success rate of 91.7%, and this reduction persisted at 12-month (p < 0.001). Patients with AFMR showed a significant functional improvement at 6- and 12-month follow-up in our series (baseline: NYHA III 70.8% IV 18.8% vs. 1-year: NYHA III 21.7% IV 0%; p < 0.001). The probability of survival free of readmission for heart failure and all-cause mortality within the first year after TMVR was 74.9%. Procedural and clinical outcomes, as well as recurrent rates of MR were similar acutely and at 1-year compared to other etiologies.
Conclusion
TMVR in patients with AFMR showed no significant differences compared to ventricular functional or degenerative/mixed MR regarding MR reduction or clinical outcomes.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 01 Oct 2021; epub ahead of print
Benito-González T, Carrasco-Chinchilla F, Estévez-Loureiro R, Pascual I, ... Alonso-Briales JH, Fernández-Vázquez F
Int J Cardiol: 01 Oct 2021; epub ahead of print | PMID: 34610357
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Abstract

LncRNA CDKN2B-AS1 hinders the proliferation and facilitates apoptosis of ox-LDL-induced vascular smooth muscle cells via the ceRNA network of CDKN2B-AS1/miR-126-5p/PTPN7.

Li J, Chen J, Zhang F, Li J, ... Cheng M, Li J
Objective
The patterns of lncRNA CDKN2B-AS1 in coronary heart disease (CHD) have been extensively studied. This study investigated the competing endogenous RNA (ceRNA) network of CDKN2B-AS1 in coronary atherosclerosis (CAS).
Methods
Microarray analyses were performed to screen out the CHD-related lncRNAs (CDKN2B-AS1) and the downstream microRNAs (miR-126-5p). The expression of CDKN2B-AS1 in serum of patients with CHD and healthy volunteers was detected. Vascular smooth muscle cells (VSMCs) were treated with oxidized low density lipoprotein (ox-LDL) to establish the cell model. Then pcDNA-CDKN2B-AS1 and/or miR-126-5p mimic were transfected into ox-LDL-treated VSMCs to estimate cell proliferation, apoptosis and inflammation. The ceRNA network of CDKN2B-AS1 along with the possible pathway in CHD was testified.
Results
CDKN2B-AS1 expression was low in patients with CHD and ox-LDL-treated VSMCs. Upon CDKN2B-AS1 overexpression, TNF-α, NF-κB and IL-1β levels in VSMCs were decreased, the proliferation of VSMCs was inhibited and the apoptosis rate was increased. Overexpression of miR-126-5p could reverse these trends. CDKN2B-AS1 as a ceRNA competitively bound to miR-126-5p to upregulate PTPN7. CDKN2B-AS1 inhibited VSMC proliferation and accelerated apoptosis by inhibiting the PI3K-Akt pathway.
Conclusion
LncRNA CDKN2B-AS1 upregulates PTPN7 by absorbing miR-126-5p and inhibits the PI3K-Akt pathway, thus hindering the proliferation and accelerating apoptosis of VSMCs induced by ox-LDL, thus being a therapeutic approach for CAS.

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

Int J Cardiol: 30 Sep 2021; 340:79-87
Li J, Chen J, Zhang F, Li J, ... Cheng M, Li J
Int J Cardiol: 30 Sep 2021; 340:79-87 | PMID: 34384839
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Impact:
Abstract

Impact of intravascular ultrasound on Outcomes following PErcutaneous coronary interventioN for In-stent Restenosis (iOPEN-ISR study).

Shlofmitz E, Torguson R, Zhang C, Mintz GS, ... Garcia-Garcia HM, Waksman R
Background
Percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) remains common. Intravascular imaging allows for the determination of the mechanism of ISR, potentially guiding appropriate therapy. Intravascular ultrasound (IVUS)-guided stent implantation is associated with a reduction in adverse events after PCI, but its impact on treatment of ISR is not clear.
Methods
All patients with 1-year follow-up after ISR treatment from 2003 through 2016 were included and stratified by IVUS use. The primary endpoint was the rate of major adverse cardiac events (MACE) at 1 year, defined as the composite of all-cause mortality, Q-wave myocardial infarction, and target vessel revascularization (TVR).
Results
The final analysis included 1522 ISR patients, 65.9% of whom were treated with IVUS guidance. The primary endpoint occurred in 18.0% of patients treated with IVUS guidance vs. 24.5% of patients treated with angiography guidance (p = 0.0014). Post-dilatation was used more often with IVUS (18.6% vs. 14.1%, p < 0.001), with a larger diameter of new stents (3.04 ± 0.35 mm vs. 2.94 ± 0.47 mm, p = 0.001). At 1 year, TVR occurred in 14.5% with IVUS guidance and 19.2% with angiography guidance (p = 0.021).
Conclusions
The use of IVUS is associated with decreased MACE at 1 year following PCI for ISR. These results support routine IVUS for the treatment of ISR lesions.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Sep 2021; 340:17-21
Shlofmitz E, Torguson R, Zhang C, Mintz GS, ... Garcia-Garcia HM, Waksman R
Int J Cardiol: 30 Sep 2021; 340:17-21 | PMID: 34371029
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Abstract

Abnormal shear stress and residence time are associated with proximal coronary atheroma in the presence of myocardial bridging.

Yong ASC, Pargaonkar VS, Wong CCY, Javadzdegan A, ... Schnittger I, Tremmel JA
Background
Atheromatous plaques tend to form in the coronary segments proximal to a myocardial bridge (MB), but the mechanism of this occurrence remains unclear. This study evaluates the relationship between blood flow perturbations and plaque formation in patients with an MB.
Methods and results
A total of 92 patients with an MB in the mid left anterior descending artery (LAD) and 20 patients without an MB were included. Coronary angiography, intravascular ultrasound, and coronary physiology measurements were performed. A moving-boundary computational fluid dynamics algorithm was used to derive wall shear stress (WSS) and peak residence time (PRT). Patients with an MB had lower WSS (0.46 ± 0.21 vs. 0.96 ± 0.33 Pa, p < 0.001) and higher maximal plaque burden (33.6 ± 15.0 vs. 14.2 ± 5.8%, p < 0.001) within the proximal LAD compared to those without. Plaque burden in the proximal LAD correlated significantly with proximal WSS (r = -0.51, p < 0.001) and PRT (r = 0.60, p < 0.001). In patients with an MB, the site of maximal plaque burden occurred 23.4 ± 13.3 mm proximal to the entrance of the MB, corresponding to the site of PRT.
Conclusions
Regions of low WSS and high PRT occur in arterial segments proximal to an MB, and this is associated with the degree and location of coronary atheroma formation.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Sep 2021; 340:7-13
Yong ASC, Pargaonkar VS, Wong CCY, Javadzdegan A, ... Schnittger I, Tremmel JA
Int J Cardiol: 30 Sep 2021; 340:7-13 | PMID: 34375705
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Impact:
Abstract

Hidden familial cardiomyopathies in children: Role of genetic testing.

Girolami F, Spinelli V, Passantino S, Bennati E, ... Olivotto I, Favilli S
Pediatric cardiomyopathies harbour significant phenotypic and genetic heterogeneity. Genetic testing is essential for the initial evaluation and the ongoing care of child and family, although challenges remain regarding its appropriate clinical implementation in minors. We here discuss the key role of genetic diagnosis in the clinical management of two patients.

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

Int J Cardiol: 30 Sep 2021; 340:55-58
Girolami F, Spinelli V, Passantino S, Bennati E, ... Olivotto I, Favilli S
Int J Cardiol: 30 Sep 2021; 340:55-58 | PMID: 34384838
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Abstract

Exercise-induced late preconditioning in mice is triggered by eNOS-dependent generation of nitric oxide and activation of PKCε and is mediated by increased iNOS activity.

Guo Y, Li Q, Xuan YT, Wu WJ, ... Tomlin A, Bolli R
The purpose of this study was to assess whether short-term, mild exercise induces protection against myocardial infarction and, if so, what role the eNOS-PKCε-iNOS axis plays. Mice were subjected to 2 bouts/day of treadmill exercise (60 min at 15 m/min) for 2 consecutive days. At 24 h after the last bout of exercise, mice were subjected to a 30-min coronary artery occlusion and 24 h of reperfusion. In the exercise group (group III, wild-type mice), infarct size (25.5 ± 8.8% of risk region) was significantly (P < 0.05) reduced compared with the control groups (sham exercise, group II [63.4 ± 7.8%] and acute myocardial infarction, group I [58.6 ± 7.0%]). This effect was abolished by pretreatment with the NOS inhibitor L-NA (group VI, 56.1 ± 16.2%) and the PKC inhibitor chelerythrine (group VIII, 57.9 ± 12.5%). Moreover, the late PC effect of exercise was completely abrogated in eNOS-/- mice (group XIII, 61.0 ± 11.2%). The myocardial phosphorylated eNOS at Ser-1177 was significantly increased at 30 min after treadmill training (exercise group) compared with sham-exercised hearts. PKCε translocation was significantly increased at 30 min after exercise in WT mice but not in eNOS-/- mice. At 24 h after exercise, iNOS protein was upregulated compared with sham-exercised hearts. The protection of late PC was abrogated in iNOS-/- mice (group XVI, 56.4 ± 12.9%) and in wildtype mice given the selective iNOS inhibitor 1400 W prior to ischemia (group X 62.0 ± 8.8% of risk region). We conclude that 1) even short, mild exercise induces a delayed PC effect that affords powerful protection against infarction; 2) this cardioprotective effect is dependent on activation of eNOS, eNOS-derived NO generation, and subsequent PKCε activation during PC; 3) the translocation of PKCε is dependent on eNOS; 4) the protection 24 h later is dependent on iNOS activity. Thus, eNOS is the trigger and iNOS the mediator of PC induced by mild exercise.

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

Int J Cardiol: 30 Sep 2021; 340:68-78
Guo Y, Li Q, Xuan YT, Wu WJ, ... Tomlin A, Bolli R
Int J Cardiol: 30 Sep 2021; 340:68-78 | PMID: 34400167
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Impact:
Abstract

EU-CaRE study: Could exercise-based cardiac telerehabilitation also be cost-effective in elderly?

Scherrenberg M, Zeymer U, Schneider S, Van der Velde AE, ... De Kluiver EP, Dendale P
Background
The role of cardiac rehabilitation (CR) is well established in the secondary prevention of ischemic heart disease. Unfortunately, the participation rates across Europe remain low, especially in elderly. The EU-CaRE RCT investigated the effectiveness of a home-based mobile CR programme in elderly patients that were not willing to participate in centre-based CR. The initial study concluded that a 6-month home-based mobile CR programme was safe and beneficial in improving VO2peak when compared with no CR.
Objective
To assess whether a 6-month guided mobile CR programme is a cost-effective therapy for elderly patients who decline participation in CR.
Methods
Patients were enrolled in a multicentre randomised clinical trial from November 11, 2015, to January 3, 2018, and follow-up was completed on January 17, 2019, in a secondary care system with 6 cardiac institutions across 5 European countries. A total of 179 patients who declined participation in centre-based CR and met the inclusion criteria consented to participate in the European Study on Effectiveness and Sustainability of Current Cardiac Rehabilitation Programs in the Elderly trial. The data of patients (n = 17) that were lost in follow-up were excluded from this analysis. The intervention (n = 79) consisted of 6 months of mobile CR programme with telemonitoring, and coaching based on motivational interviewing to stimulate patients to reach exercise goals. Control patients did not receive any form of CR throughout the study period. The costs considered for the cost-effectiveness analysis of the RCT are direct costs 1) of the mobile CR programme, and 2) of the care utilisation recorded during the observation time from randomisation to the end of the study. Costs and outcomes (utilities) were compared by calculation of the incremental cost-effectiveness ratio.
Results
The healthcare utilisation costs (P = 0.802) were not significantly different between the two groups. However, the total costs were significantly higher in the intervention group (P = 0.040). The incremental cost-effectiveness ratio for the primary endpoint VO2peak at 6 months was €1085 per 1-unit [ml/kg/min] improvement in change VO2peak and at 12 months it was €1103 per 1 unit [ml/kg/min] improvement in change VO2peak. Big differences in the incremental cost-effectiveness ratios for the primary endpoint VO2peak at 6 months and 12 months were present between the adherent participants and the non-adherent participants.
Conclusion
From a health-economic point of view the home-based mobile CR programme is an effective and cost-effective alternative for elderly cardiac patients who are not willing to participate in a regular rehabilitation programme to improve cardiorespiratory fitness. The change of QoL between the mobile CR was similar for both groups. Adherence to the mobile CR programme plays a significant role in the cost-effectiveness of the intervention. Future research should focus on the determinants of adherence, on increasing the adherence of patients and the implementation of comprehensive home-based mobile CR programmes in standard care.

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

Int J Cardiol: 30 Sep 2021; 340:1-6
Scherrenberg M, Zeymer U, Schneider S, Van der Velde AE, ... De Kluiver EP, Dendale P
Int J Cardiol: 30 Sep 2021; 340:1-6 | PMID: 34419529
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Impact:
Abstract

Association of hospital performance measures with readmissions for patients with heart failure: A report from JROAD-DPC study.

Nakao K, Yasuda S, Noguchi T, Sumita Y, ... Gale CP, Ogawa H
Background
Measuring quality of care is central to quality improvement. Improving outcomes for heart failure (HF) may relate to hospital care delivery. However, there is limited nationwide data on the relationship between hospital-level HF performance measures and clinical outcomes.
Methods
From the Japanese Registry of All cardiac and vascular Diseases (JROAD-DPC) database, 83,567 HF patients hospitalised in 731 certificated hospitals in 2014 by the Japanese Circulation Society were analysed. Five performance measures were prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist and measurement rate of echocardiography and B-type natriuretic peptide during hospitalisation. Relationships between these measures and 1-year readmission due to HF were analysed. Composite performance score (CPS) obtained from the five performance measures and outcomes were also analysed. We also investigated the relationships between CPS and hospital structural factors.
Results
From the cohort (mean age; 78.2 years, woman 48.4%), HF readmission rate at 1 year was 19.6% (n = 16,368). Readmission rate decreased with higher quartiles of prescription rate in each medication and diagnostic performance rates. The highest CPS group was associated with a 15% risk reduction in HF readmission compared with the lowest CPS group (hazard ratio, 0.85, 95% confidence interval [0.80-0.89], p < 0.001) after covariate adjustment. Several structural factors such as number of cardiology specialists, hospital case volume for HF, and presence of cardiac surgery division were associated with high CPS.
Conclusion
Higher hospital performance measures for HF were inversely associated with HF readmissions.

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

Int J Cardiol: 30 Sep 2021; 340:48-54
Nakao K, Yasuda S, Noguchi T, Sumita Y, ... Gale CP, Ogawa H
Int J Cardiol: 30 Sep 2021; 340:48-54 | PMID: 34419528
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Impact:
Abstract

Detection of hypertrophic cardiomyopathy by an artificial intelligence electrocardiogram in children and adolescents.

Siontis KC, Liu K, Bos JM, Attia ZI, ... Noseworthy PA, Ackerman MJ
Background
There is no established screening approach for hypertrophic cardiomyopathy (HCM). We recently developed an artificial intelligence (AI) model for the detection of HCM based on the 12‑lead electrocardiogram (AI-ECG) in adults. Here, we aimed to validate this approach of ECG-based HCM detection in pediatric patients (age ≤ 18 years).
Methods
We identified a cohort of 300 children and adolescents with HCM (mean age 12.5 ± 4.6 years, male 68%) who had an ECG and echocardiogram at our institution. Patients were age- and sex-matched to 18,439 non-HCM controls. Diagnostic performance of the AI-ECG model for the detection of HCM was estimated using the previously identified optimal diagnostic threshold of 11% (the probability output derived by the model above which an ECG is considered to belong to an HCM patient).
Results
Mean AI-ECG probabilities of HCM were 92% and 5% in the case and control groups, respectively. The area under the receiver operating characteristic curve (AUC) of the AI-ECG model for HCM detection was 0.98 (95% CI 0.98-0.99) with corresponding sensitivity 92% and specificity 95%. The positive and negative predictive values were 22% and 99%, respectively. The model performed similarly in males and females and in genotype-positive and genotype-negative HCM patients. Performance tended to be superior with increasing age. In the age subgroup <5 years, the test\'s AUC was 0.93. In comparison, the AUC was 0.99 in the age subgroup 15-18 years.
Conclusions
A deep-learning, AI model can detect pediatric HCM with high accuracy from the standard 12‑lead ECG.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 30 Sep 2021; 340:42-47
Siontis KC, Liu K, Bos JM, Attia ZI, ... Noseworthy PA, Ackerman MJ
Int J Cardiol: 30 Sep 2021; 340:42-47 | PMID: 34419527
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Impact:
Abstract

Cardiovascular implantable electronic device therapy in patients with left ventricular assist devices: insights from TRAViATA.

Darden D, Ammirati E, Brambatti M, Lin A, ... Adler E, Braun OÖ
Background
There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs.
Methods
Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111).
Results
A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166-701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42-5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D.
Conclusion
In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV‑lead pacing post LVAD implantation.

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

Int J Cardiol: 30 Sep 2021; 340:26-33
Darden D, Ammirati E, Brambatti M, Lin A, ... Adler E, Braun OÖ
Int J Cardiol: 30 Sep 2021; 340:26-33 | PMID: 34437934
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Impact:
Abstract

Generalizability of the REDUCE-IT trial and cardiovascular outcomes associated with hypertriglyceridemia among patients potentially eligible for icosapent ethyl therapy: An analysis of the REduction of Atherothrombosis for Continued Health (REACH) registry.

Picard F, Bhatt DL, Ducrocq G, Ohman EM, ... Elbez Y, Steg PG
Background
The REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) trial demonstrated that high-dose icosapent-ethyl reduced the risk of ischemic events in statin-treated patients with elevated triglycerides (TG) and either atherosclerotic cardiovascular disease (ASCVD) or diabetes plus at least one risk factor.
Methods and results
Using data from REACH (Reduction of Atherothrombosis for Continued Health), a large international registry of outpatients with or at risk of ASCVD, we evaluated the proportion of patients potentially eligible for enrolment in REDUCE-IT and compared their outcomes to those excluded because of low TG. Among 62,464 patients with either ASCVD or diabetes enrolled in the REACH Registry, 1036/8418 (12.3%) patients in primary prevention and 6049/54046 (11.2%) patients in secondary prevention (11.3% overall) would have been eligible for inclusion in REDUCE-IT. Compared with patients excluded for low TG level, adjusted risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, unstable angina, or coronary revascularization was higher in the REDUCE-IT eligible group (HR:1.06, 95%CI:1.00-1.13, p = 0.04). In addition, unstable angina, non-fatal MI, percutaneous coronary intervention and coronary artery bypass grafting were also more frequent in the REDUCE-IT eligible group (HR:1.17, 95%CI:1.07-1.27, p < 0.001; HR:1.25, 95%CI:1.07-1.45, p < 0.001; HR:1.42, 95%CI:1.27-1.57, p < 0.001; HR:1.43, 95%CI:1.19-1.71, p < 0.001, respectively), whereas the adjusted risk of non-fatal stroke was lower (HR:0.64, 95%CI:0.54-0.75, p < 0.001).
Conclusion
In this large international registry of patients with or at high-risk of ASCVD, 11.3% met the REDUCE-IT trial selection criteria. REDUCE-IT eligible patients were found to be at higher risk of cardiac atherothrombotic events, but at lower risk of stroke than trial-ineligible patients with lower TG.

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

Int J Cardiol: 30 Sep 2021; 340:96-104
Picard F, Bhatt DL, Ducrocq G, Ohman EM, ... Elbez Y, Steg PG
Int J Cardiol: 30 Sep 2021; 340:96-104 | PMID: 34450192
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Abstract

Mortality and years of life lost of cardiovascular diseases in China, 2005-2020: Empirical evidence from national mortality surveillance system.

Wang W, Liu Y, Liu J, Yin P, ... Wang F, Zhou M
Objectives
Cardiovascular disease (CVD) is leading cause of death in China. We aimed to provide national and subnational estimates and its change of premature mortality burden of CVD during 2005-2020.
Methods
Data from multi-source on the basis of national mortality surveillance system (NMSS) was used to estimate mortality and years of life lost (YLL) of total CVD and its subcategories in Chinese population across 31 provinces during 2005-2020.
Results
Estimated CVD deaths increased from 3.09 million in 2005 to 4.58 million in 2020; the age-standardized mortality rate (ASMR) decreased from 286.85 per 100,000 in 2005 to 245.39 per 100,000 in 2020. A substantial reduction of 19.27% of CVD premature mortality burden, as measured by age-standardized YLL rate, was observed. Ischemic heart disease (IHD), hemorrhagic stroke (HS) and ischemic stroke (IS) were leading 3 causes of CVD death. Marked differences were observed in geographical patterns for total CVD and its subcategories, and it appeared to be lower in areas with higher economic development. Population ageing was dominant driver contributed to CVD deaths increase, followed by population growth. And, age-specific mortality shifts contributed largely to CVD deaths decline in most provinces.
Conclusion
Substantial discrepancies were demonstrated in CVD premature mortality burden across China. Targeted considerations were needed to integrate primary care with clinical care through intensifying further strategies for reducing CVD mortality among specific subcategories, high risk population and regions with inadequate healthcare resources.

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

Int J Cardiol: 30 Sep 2021; 340:105-112
Wang W, Liu Y, Liu J, Yin P, ... Wang F, Zhou M
Int J Cardiol: 30 Sep 2021; 340:105-112 | PMID: 34453974
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Abstract

Acute-phase initiation of cardiac rehabilitation and clinical outcomes in hospitalized patients for acute heart failure.

Kaneko H, Itoh H, Kamiya K, Morita K, ... Yasunaga H, Komuro I
Background
Extensive data support the clinical benefit of cardiac rehabilitation (CR) for patients with chronic heart failure (HF). However, whether CR could be beneficial for patients hospitalized for acute heart failure remains unclear.
Methods
We retrospectively analyzed data from the Diagnosis Procedure Combination database, a nationwide inpatient database. We included patients hospitalized for HF, who were aged ≥20 years and with New York Heart Association class ≥II, between January 2010 and March 2018. We excluded patients with length of hospital stay ≤2 days, those undergoing major procedures under general anesthesia, those requiring advanced mechanical supports within 2 days after admission, and those with disturbance of consciousness. Propensity score matching and instrumental variable analyses were conducted to compare clinical outcomes between the patients with and without acute-phase initiation of CR defined as initiation of CR within two days after hospital admission.
Results
Among 430,216 eligible patients, 63,470 patients (14.8%) received the acute-phase initiation of CR. Propensity score matching created 63,470 pairs and found that the acute-phase initiation of CR was associated with lower in-hospital mortality (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.73-0.80), shorter hospital stay and lower incidence of 30-day readmission due to HF. The instrumental variable analysis also showed patients with acute-phase initiation of CR was associated with lower in-hospital mortality than those without (OR, 0.73; 95% CI, 0.68-0.79).
Conclusion
Our analysis suggested a potential benefit of acute-phase initiation of CR for short-term clinical outcomes in hospitalized patients with acute HF.

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

Int J Cardiol: 30 Sep 2021; 340:36-41
Kaneko H, Itoh H, Kamiya K, Morita K, ... Yasunaga H, Komuro I
Int J Cardiol: 30 Sep 2021; 340:36-41 | PMID: 34454966
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Abstract

Prognosis of patients with acute pulmonary embolism and discordant right ventricle strain serum biomarkers.

Seropian IM, Chiabrando JG, Damonte JI, Halsband AL, ... Berrocal DH, Bluro IM
Background
Right ventricle strain serum biomarkers, such as high-sensitivity cardiac troponin T (hs-cTnT) and NT-pro-brain natriuretic peptide (NT-proBNP), are prognostic in patients with pulmonary embolism (PE). Prognosis accuracy in patients with discordancy between serum biomarkers remains, however, unknown.
Methods
We performed a retrospective analysis in patients with intermediate or high risk PE and discordant serum biomarkers of RV strain as follows: high hs-cTnT and low NT-proBNP (\'high troponin discordance\'), compared to patients with low hs-cTnT and high NT-proBNP (\'high NT-proBNP discordance\'). Cut-off values for high hs-cTnT were ≥14 pg/mL in patients <75 years and ≥45 pg/mL in patients >75-year. Cut-off values for high NT-proBNP were ≥600 pg/mL. The primary end-point was a composite of death, resuscitated cardiac arrest, mechanical ventilation, and inotrope use at one month. \'High troponin discordance\', age, sex and body mass index (BMI) were included in a logistic regression model. Time to event analysis was performed using Kaplan Meier curves and Log-rank test.
Results
73 patients were included. \'High troponin discordance\' patients (n=41) were younger, presented with a higher heart rate, more frequent bilateral PE, and received more thrombolytics as treatment compared with \'high NT-proBNP discordance\' patients (n = 32). Primary end-point was significantly higher in the \'high troponin discordance\' patients (29.3% vs 9.4%, p=0.045). \'High troponin discordance\' was independently associated with the primary end-point after adjusting for age, sex and BMI. Log rank test confirmed worse outcome in the high troponin discordance group (p=0.037).
Conclusions
High troponin discordance\' patients with intermediate/high risk PE, had worse outcomes than patients with high BNP discordance.

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

Int J Cardiol: 30 Sep 2021; 340:88-93
Seropian IM, Chiabrando JG, Damonte JI, Halsband AL, ... Berrocal DH, Bluro IM
Int J Cardiol: 30 Sep 2021; 340:88-93 | PMID: 34454965
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Abstract

The usefulness of left ventricular volume and aortic diastolic flow reversal for grading chronic aortic regurgitation severity - Using cardiovascular magnetic resonance as reference.

Gao SA, Polte CL, Lagerstrand KM, Bech-Hanssen O
Echocardiographic evaluation of chronic aortic regurgitation (AR) severity can lead to diagnostic ambiguity due to few feasible parameters or incongruent findings. The aim of the present study was to improve the diagnostic usefulness of left ventricular (LV) enlargement and aortic end-diastolic flow velocity (EDFV) using cardiovascular magnetic resonance (CMR) as reference. Patients (n = 120) were recruited either prospectively (n = 45) or retrospectively (n = 75). Severe AR (CMR regurgitant fraction > 33%) was present in 51% and 93% of the patients had LV ejection fraction ≥ 50%. EDFV and LV end-diastolic volume index (EDVI) were assessed by echocardiography using the traditional (excluding trabeculae) and recommended approach (including trabeculae). The patients were randomised to a derivation (n = 60) or a test group (n = 60). EDVI (traditional/recommended) to rule in (>99/118 ml/m2) and rule out severe AR (≤75/87 ml/m2) were identified using ROC analyses in the derivation group. The corresponding thresholds for EDFV were >17 cm/s and ≤10 cm/s. In the test group, the positive/negative likelihood ratios to rule in/rule out severe AR using EDVI were 10.0/0.14 (traditional), 6.2/0.11 (recommended), and using EDFV were 10.2/0.08. To rule in and rule out severe AR using derived cut-off values instead of >2 SD reduced the false positives by 92%, whereas using EDFV ≤10 cm/s instead of ≤20 cm/s reduced the false negatives by 94%. In conclusion, EDVI and EDFV as quantitative parameters are useful to rule in or rule out severe chronic AR. Importantly, other causes of LV enlargement have to be considered.

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

Int J Cardiol: 30 Sep 2021; 340:59-65
Gao SA, Polte CL, Lagerstrand KM, Bech-Hanssen O
Int J Cardiol: 30 Sep 2021; 340:59-65 | PMID: 34474096
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Abstract

Associations of cardiac injury biomarkers with risk of peripheral artery disease: The Multi-Ethnic Study of Atherosclerosis.

Garg PK, Lima J, deFilippi CR, Daniels LB, ... Criqui MH, Bahrami H
Introduction
We investigated the associations of high-sensitivity cardiac Troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with risk of developing clinical peripheral artery disease (PAD) or a low ankle-brachial index (ABI).
Methods
Hs-cTnT and NT-proBNP were measured in 6692 and 5458 participants respectively without baseline PAD between 2000 and 2002 in the Multi-ethnic Study of Atherosclerosis. A significant number also had repeat biomarker measurement between 2004 and 2005. Incident clinical PAD was ascertained through 2017. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15 from baseline, was assessed among 5920 eligible individuals who had an ABI >0.9 at baseline and at least one follow-up ABI measurement 3-10 years later. Multivariable Cox proportional hazards and logistic regression modeling were used to determine the association of these biomarkers with clinical PAD and low ABI, respectively.
Results
Overall, 121 clinical PAD and 118 low ABI events occurred. Adjusting for demographic and clinical characteristics, each log unit increment in hs-cTnT and NT-proBNP was associated with a 30% (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.1, 1.6) and 50% (HR) 1.5, 95% CI: 1.2, 1.8) higher risk of clinical PAD respectively. No significant associations were observed for incident low ABI. Change in these biomarkers was not associated with either of the PAD outcomes.
Conclusions
NT-proBNP and hs-cTnT are independently associated with the development of clinical PAD. Further study should determine whether these biomarkers can help to better identify those at higher risk for PAD.

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

Int J Cardiol: 30 Sep 2021; epub ahead of print
Garg PK, Lima J, deFilippi CR, Daniels LB, ... Criqui MH, Bahrami H
Int J Cardiol: 30 Sep 2021; epub ahead of print | PMID: 34600979
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Abstract

The impact of computed tomography-derived aortic atheroma volume on prognosis after transcatheter aortic valve replacement.

Fujita H, Toba T, Miwa K, Suzuki M, ... Kono A, Hirata KI
Background
The impact of the extent of aortic atheroma on patients\' prognosis after transcatheter aortic valve replacement (TAVR) has not been completely evaluated. This study aimed to evaluate the prognostic value of the aortic atheroma volume (AAV) derived from computed tomography, and the effect of its differences among the segments of the aorta, in patients undergoing TAVR.
Methods
In total, 143 patients with symptomatic severe aortic stenosis who underwent pre-procedural computed tomography before TAVR procedure indication were evaluated. AAV was calculated by measuring the aortic lumen and vessel volume using every 1-mm axial image and was further divided into thoracic (TAAV) and abdominal segments (AbAAV).
Results
During a median follow-up of 651 days, 24 all-cause and 14 cardiac deaths occurred. In the Kaplan-Meier analysis, the high AAV group had significantly higher all-cause and cardiac mortalities than the low AAV group (p = 0.016 and 0.023, respectively). Regarding segmental AAV, all-cause and cardiac mortalities did not have significant differences between the high and low TAAV groups. Moreover, all-cause and cardiac mortalities were significantly higher in the high AbAAV group than in the low AbAAV group (p = 0.0043 and 0.023, respectively). The multivariable analysis showed that only AbAAV was an independent predictor for all-cause mortality (hazard ratio: 1.06, p = 0.046).
Conclusion
AAV was significantly associated with the mortality after TAVR. The current study suggests the pre-procedural assessment of AAV is valuable in predicting prognosis after TAVR. However, further investigation with a larger sample size is needed to validate our findings.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 29 Sep 2021; epub ahead of print
Fujita H, Toba T, Miwa K, Suzuki M, ... Kono A, Hirata KI
Int J Cardiol: 29 Sep 2021; epub ahead of print | PMID: 34600978
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Abstract

Instantaneous wave-free ratio compared with fractional flow reserve in PCI: A cost-minimization analysis.

Berntorp K, Persson J, Koul SM, Patel MR, ... Fröbert O, Götberg M
Background
Coronary physiology is a routine diagnostic tool when assessing whether coronary revascularization is indicated. The iFR-SWEDEHEART trial demonstrated similar clinical outcomes when using instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) to guide revascularization. The objective of this analysis was to assess a cost-minimization analysis of iFR-guided compared with FFR-guided revascularization.
Methods
In this cost-minimization analysis we used a decision-tree model from a healthcare perspective with a time-horizon of one year to estimate the cost difference between iFR and FFR in a Nordic setting and a United States (US) setting. Treatment pathways and health care utilizations were constructed from the iFR-SWEDEHEART trial. Unit cost for revascularization and myocardial infarction in the Nordic setting and US setting were derived from the Nordic diagnosis-related group versus Medicare cost data. Unit cost of intravenous adenosine administration and cost per stent placed were based on the average costs from the enrolled centers in the iFR-SWEDEHEART trial. Deterministic and probabilistic sensitivity analyses were carried out to test the robustness of the result.
Results
The cost-minimization analysis demonstrated a cost saving per patient of $681 (95% CI: $641 - $723) in the Nordic setting and $1024 (95% CI: $934 - $1114) in the US setting, when using iFR-guided compared with FFR-guided revascularization. The results were not sensitive to changes in uncertain parameters or assumptions.
Conclusions
IFR-guided revascularization is associated with significant savings in cost compared with FFR-guided revascularization.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 29 Sep 2021; epub ahead of print
Berntorp K, Persson J, Koul SM, Patel MR, ... Fröbert O, Götberg M
Int J Cardiol: 29 Sep 2021; epub ahead of print | PMID: 34600977
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