bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV-infected patients display increased proatherogenic anti-apolipoprotein A1 autoantibodies, inflammatory and metabolomic markers
Authors: Frias M , Pagano S , Nasim B , Sidibe J , Kamau F , Lecour S , Strijdom H , Thomas A , Vuilleumier N
Published: October 2021

Background

HIV-infected patients display an increased risk of cardiovascular events. HIV and antiretroviral therapy (ART) have both been suggested to increase this risk but their specific role remains unclear. Autoantibodies against apolipoprotein A1 (anti-apoA1 IgG) are also associated with cardiovascular risk. The aim of this study was to analyse anti-apoA1 IgG levels and inflammatory markers as well as the metabolomic profile in a cohort of HIV-free, ART-experienced and naïve HIV-infected patients.

Methods

144 participants from a South African cohort were categorised into HIV-free (n=50), HIV-infected/ART-experienced (n=50) and HIV-infected/ART-naïve (n=44) groups. The levels of anti-apoA1 IgG were assessed by homemade ELISA assays. We performed targeted metabolomic analyses using standard operating procedures and measured inflammatory biomarkers using the Meso Scale Discovery® platform. Additionally, we conducted in vitro experiments on human aortic endothelial cells treated with anti-apoA1 IgG and assessed levels of adhesion molecules.

Results

Inflammatory markers (IFNg, IL-6, IL-10, TNFa, CRP all p<0.05), circulating adhesion molecules (ICAM-1 and VCAM-1, p<0.05), anti-apoA1 IgG levels were increased in HIV-infected patients compared to HIV-free participants.

While ART treatment significantly reduced IFNg, IL-10, TNFa, VCAM-1, anti-apoA1 IgG levels, no significant differences were observed in other biomarkers between ART-experienced and naïve participants. Treatment of human aortic endothelial cells with anti-apoA1 IgG (40μg/ml) induced a significant increase in these adhesion molecules compared to cells treated with control IgG (40μg/ml). Metabolomic analyses identified 257 endogenous circulating metabolites in plasma. Among these metabolites, we found that in HIV-free and infected patients 14 and 17 metabolites were significantly correlated with anti-apoA1 IgG levels, respectively. Among these 17 metabolites, 2 were positively correlated with the tryptophan pathway; kynurenine (r=0.292, p=0.0069) and 5-hydroxyindolacetate (r=0.316, p=0.0019). Interestingly, kynurenine was not significantly correlated with anti-apoA1 IgG levels in HIV-free patients.

Conclusion

HIV-infected patients displayed a more proatherogenic profile compared to HIV-free subjects. Anti-apoA1 IgG induced adhesion molecules expression. Metabolomics identified metabolites that were significantly associated with anti-apoA1 IgG levels and inflammatory biomarkers known to underlie atherosclerosis burden.

Funding Acknowledgement

Type of funding sources: None.
Association of soluble ST2 and right ventricular dysfunction with mortality in chronic hemodialysis patients
Authors: Romero-Gonzalez G , Diaz-Dorronsoro I , Ravassa S , Lopez B , Gonzalez A , Diez J
Published: October 2021

Background

End stage kidney disease (ESKD), is a triggering and facilitating factor for cardiac remodelling (i.e., morphologic hypertrophy and/or dilatation associated with deterioration of systolic and/or diastolic function) that contribute to heart failure (HF). RV dysfunction (RVD) has been demonstrated to predict mortality in ESKD patients.

Purpose

The present study aimed to investigate the potential associations between RVD and circulating biomarkers of myocardial inflammation and fibrosis with all-cause mortality in HD patients.

Method

We performed a retrospective single-centre cohort study of prevalent patients admitted in a chronic HD program for more than 3 months. Clinical characteristics and echocardiographic parameters were assessed in all patients. Pre-dialysis blood samples for measurement of inflammatory (e.g., C reactive protein, interleukin-1, interleukin-18) and fibrotic (e.g., soluble suppression of tumorigenesis-2 [sST2], galectin-3, C-terminal pro-peptide of procollagen type I and N-terminal pro-peptide of procollagen type III) biomarkers were collected. RVD was defined using tricuspid annular plane systolic excursion (TAPSE) <1.7 cm or pulsed Doppler peak annular velocity (S') <9.5 cm/s. The ability of sST2 to discriminate between mortality was assessed using AuROC curve.

Results

We enrolled forty-eight patients, mean patients age was 74 (64 – 79)years, and 62.5% were males. 95.8% of the patients had high blood pressure, and at least 70.8% had HF criteria. About 52.1% of the patients were on OnLine HDF. Regarding the echocardiogram parameters, 56.3% had no functional heart disease, 10.4% had LVD (LVEF ≤45% and diastolic dysfunction ≥ grade 2), and 33.3% had RVD (TAPSE <17mm and/or S'<9.5cm/s), with or without LVD. Mortality was higher 45.5% (log-rank, p=0.003) in patients with RVD as diagnosed by S' than in patients without RVD. No difference in mortality was observed for RVD defined by TAPSE. There were no differences in the morphology and function parameters of the left ventricle between patients with and without RVD. From all biomarkers measured only sST2 was associated with RVD. Indeed, an age- and sex-adjusted analyses showed that doubling of sST2 was inversely associated with a decreased in S' (estimate = −2.03, 95% CI [−3.04 to −1.00] cm/s; P=0.002). Mortality was increased in patients with sST2 ≥40.45 ng/mL compared to patients with sST2 <40.45 ng/mL (66.7% vs. 18.9%, log-rank; p=0.004).

Conclusion

This preliminary data would suggest that patients on chronic HD, circulating levels of sST2 were independently associated with RVD. In addition, elevated sST2 levels and RVD were associated with increased all-cause mortality. The myocardial pro-remodelling effect of sST2 in HD patients with RVD warrants further investigation.

Funding Acknowledgement

Type of funding sources: None.
Acute kidney injury in patients undergoing transcatheter aortic valve replacement: insights on clinical outcomes and prognostic factors
Authors: Munoz-Garcia M , Munoz-Garcia E , Munoz Garcia A J , Dominguez-Franco A J , Jimenez-Navarro M F , Alonso-Briales J H , Hernandez-Garcia J M , Gomez-Doblas J J
Published: October 2021

Acute Kidney Injury (AKI) after cardiac surgery is associated with increased mortality, but very few data exist on the occurrence of AKI associated with Transcatheter Aortic Valve Replacement (TAVR). The aim of this study was to determine the frequency and prognosis of AKI after transcatheter aortic valve replacement.

Methods

Between April 2008 and December 2019, 751 patients with severe aortic stenosis underwent to TAVR. The AKI was defined according to Valve set by the Academic Research Consortium, as the absolute increase in serum creatinine ≥0.3 mg/dl at 72 hours a percutaneous procedure.

Results

AKI was identified in 127 patients (16.9%) and 3 patients required renal replacement therapy. After implantation there was a slight improvement in renal function, baseline serum creatinine decreased from 1.37±0.9mg/dl to 1.22±0.6 mg/dl, p=0.01 and glomerular filtration rate (GFR) increased from 49.7±20 to 53.9±22, p<0.001.

In patients with AKI, the mortality at 30 days was 12.6% compared to 1.3% of patients without AKI, [OR=11.08 (95% CI 4.631–26.514) p<0.001] and late mortality after a mean of 49.4±27 months, was 40.2% in those patients with AKI compared to 37.9% in those without AKI, [OR=1.101 (95% CI 0.730–1.662), p=0.360]

In the multivariate analysis AKI was an independent predictor of cumulative total mortality [HR=1.644 (95% CI 1.230–2.198), p=0.001] and threatening bleeding [HR=3.623 (95% CI 1.448–8.764), p=0.004], but not cardiovascular mortality [HR=1.496 (95% CI 0,834.2.682), p=0.177]; readmission by heart failure [HR=1.249 (95% CI 0.652–2.392), p=0.502], myocardial infarction [HR=1.929 (95% CI 0.705–5.287), p=0.201]; or stroke [HR=1.662 (95% CI 0.874–3.142), p=0.118].

The predictors of AKI were: general anesthesia [HR=2.112 (1.038–4.246), p=0.039]; the first generation aortic prostheses [HR=3.485 (95% CI 2.211–5.442), p=0.001]; tricuspid regurgitation [HR=1.604 (95% CI 1.057–2.435), p=0.026] and renal chronic failure [HR=2.060 95% CI 1.148–3.699); p=0.015].

Conclusions

Deterioration of renal function in patients undergoing TAVR is a serious and frequent complication. The occurrence of AKI was associated with increase early mortality and also was a predictor of worse outcomes throughout 3.65±2 years of follow-up.

Funding Acknowledgement

Type of funding sources: None.
A safety and clinical efficacy analysis of PCSK9 monoclonal antibodies in patients with markedly elevated creatine phosphokinase levels
Authors: Zafrir B , Hislop E , Volis I , Saliba W
Published: October 2021

Introduction

PCSK9 inhibitors have been used in statin intolerant patients to reduce low-density lipoprotein cholesterol (LDL-C) safely and effectively. However, evidence is lacking regarding the safety and clinical utility of PCSK9 inhibition in patients with markedly elevated creatine phosphokinase (CPK) levels.

Methods

We searched a large HMO database for patients with CPK levels above 1000 U/L, who were initiating PCSK9 inhibition therapy (Jan 2016–Dec 2019). The patients' treatment plans, adherence, CPK and LDL-C levels were analyzed.

Results

Of the1600 patients initiating PCSK9 inhibitors, 26 met study criteria, and all were previously treated by statins (in 18 patients ≥3 different statin types were prescribed). Myalgia was evident in most patients (n=24), and 5 were clinically diagnosed with rhabdomyolysis. Abnormal liver function tests were noted in 8 of the 26 patients. Most were very-high cardiovascular risk patients, with concurrent atherosclerotic cardiovascular disease (n=17) and baseline LDL-C levels >190 mg/dL (n=19). Peak CPK levels ranged from 1050–53540 U/L [median (IQR), 3687 (1876–8344)]. Concomitant secondary factors for CPK elevation included renal failure (n=5), inflammatory rheumatoid disorders (n=3), severe hypothyroidism (n=3), intensive exercise (n=2), nephrotic range proteinuria (n=1) and genetic muscular disease (n=1). The monoclonal antibodies, Alirocumab and Evolocumab, were initiated in 12 and 14 patients respectively. In 24 patients (92%) CPK reduction of >50% was noted and in 12 patients (46%) CPK levels returned to normal range (Figure). Under PCSK9 inhibition, 17 patients (65%) achieved LDL-C levels <70 mg/dL and in 12 patients (46%) LDL-C was <55 mg/dL. Only 2 patients discontinued PCSK9 inhibitors.

Conclusions

High-risk patients with markedly elevated CPK levels, can safely reduce LDL-C levels with PCSK9 inhibitors, and although statin intolerance is a major cause of elevated CPK, other predisposing and precipitating factors are common.

Funding Acknowledgement

Type of funding sources: None.
Acute arterial events across all vascular territories in the FOURIER trial
Authors: Oyama K , Giugliano R , Tang M , Bonaca M , Saver J , Murphy S , Ruzza A , Sever P , Sabatine M , Bergmark B
Published: October 2021

Background

In the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trial, adding the PCSK9 inhibitor evolocumab to statin therapy reduced low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk. Although atherosclerotic coronary, cerebrovascular, and peripheral vascular events share a related pathobiology, the effect of aggressive LDL-C lowering with PCSK9 inhibition on the risk of acute arterial events across all three vascular beds is not well-described.

Purpose

To assess the efficacy of evolocumab on acute arterial events in all vascular territories including coronary, cerebral, and peripheral vascular beds.

Methods

In the FOURIER trial, patients (n=27,564) with stable atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on a statin were randomly assigned to evolocumab versus placebo and followed for a median of 2.2 years (1.8–2.5). Acute arterial events were defined as a composite of coronary (coronary heart disease [CHD] death, myocardial infarction [MI], or urgent coronary revascularization), cerebrovascular (ischemic stroke, transient ischemic attack [TIA], or urgent cerebral revascularization), or peripheral vascular (acute limb ischemia, major amputation, or urgent peripheral revascularization) events. Cox proportional-hazard models were used to assess the efficacy of evolocumab on these outcomes. Landmark and total event analyses were also done.

Results

Of the 2,210 first acute arterial events occurring during follow-up, 74% were coronary, 22% were cerebrovascular, and 4% were peripheral vascular. Evolocumab reduced the risk of a first acute arterial event by 19% (HR 0.81, 95% CI 0.74–0.88; P<0.001), with significant individual reductions in acute coronary (HR 0.83; 95% CI 0.75–0.91; P<0.001), acute cerebrovascular (HR 0.77; 95% CI 0.65–0.92; P=0.004), and acute peripheral vascular (HR 0.58; 95% CI 0.38–0.88; P=0.01) events (Figure, top). The magnitude of the risk reduction with evolocumab tended to increase over time, with a 16% reduction (HR 0.84; 95% CI 0.75–0.96) in the first year followed by a 24% reduction (HR 0.76; 95% CI 0.67–0.85) thereafter (Figure, bottom). There were 3,780 total acute arterial events (first plus recurrent), with a 22% reduction with evolocumab (incidence rate ratio [RR] 0.78; 95% CI 0.70–0.87). Evolocumab prevented 496 total acute arterial events as compared to 222 first events.

Conclusions

The addition of the PCSK9 inhibitor evolocumab to statin therapy reduced the risk of acute arterial events across all vascular territories with a robust effect over time. These findings indicate a pan-vascular impact of aggressive lipid-lowering therapy on these acute and clinically meaningful events.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): The FOURIER trial was supported by Amgen.
Sodium-glucose co-transporter-2 inhibitors and the risk of major arrhythmias: a meta-analysis of the cardiovascular and renal outcome trials
Authors: Boulmpou A , Patoulias D , Teperikidis E , Papadopoulos C E , Sarafidis P , Doumas M , Fragakis N , Pagourelias E , Vassilikos V
Published: October 2021

Background

Type 2 diabetes mellitus is closely associated with cardiovascular disease and evidence already exists on its arrhythmogenic action. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a unique class of oral antidiabetic medications which recently attracted attention for reducing the total risk of major adverse cardiovascular events in a series of recent, large placebo-controlled randomized clinical trials (RCTs). Dapagliflozin and empagliflozin additionally seem to improve survival and outcomes in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of the presence of diabetes mellitus. Whether antidiabetic treatment with sodium-glucose co-transporter inhibitors could reduce the arrhythmic burden in diabetic patients still is to be clarified.

Purpose

The purpose of the present meta-analysis was to report the impact of SGLT2i on the risk for several types of cardiac arrhythmias, pooling data from all relevant cardiovascular and renal outcome, placebo-controlled, RCTs, comparing SGLT2i to placebo.

Methods

We searched PubMed for all available cardiovascular and renal outcome RCTs utilizing SGLT2i, along with grey literature sources. We sought to determine the risk of the following arrhythmias/cardiac disorders with the use of SGLT2i versus placebo: atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, ventricular extrasystoles, sinus bradycardia, sinus node dysfunction, second degree atrioventricular block, complete atrioventricular block.

Results

We extracted relevant data from 8 trials (5 dedicated cardiovascular outcome trials, 2 dedicated renal outcome trials, 1 trial enrolling patients with HFrEF), pooling data in a total of 55,966 patients. SGLT-2i treatment compared to placebo produced a significant reduction in the risk of atrial fibrillation equal to 21% (RR=0.79, 95% CI: 0.67–0.93, I2=0%) (Figure 1). A non-significant reduction in the risk of atrial flutter equal to 9% (RR=0.91, 95% CI: 0.64–1.29, I2=0%) was also observed with SGLT2i (Figure 2). No significant effect on the rest major arrhythmias was observed.

Conclusions

Antidiabetic therapy with SGLT2i seems to hold a significant impact on antiarrhythmic burden in type 2 diabetes mellitus, reducing the risk of atrial fibrillation development.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Meta-analysis of cardiovascular outcome trials assessing the cardiovascular efficacy and safety of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus
Authors: Patoulias D , Boulmpou A , Teperikidis E , Katsimardou A , Siskos F , Tranidou A , Nikolaidis A , Mouselimis D , Doumas M , Papadopoulos C E , Vassilikos V
Published: October 2021

Background

Type 2 diabetes mellitus (T2DM) represents an independent risk factor for the development of cardiovascular disease, which accounts for half of deaths among the affected patients. Patients with T2DM experience higher incidence of vascular interventions compared to high-risk patients without T2DM or cardiovascular disease at baseline, underscoring the necessity for targeted therapeutic interventions. Dipeptidyl peptidase-4 (DPP-4) inhibitors constitute a safe treatment option with fair glycemic efficacy in T2DM whose cardiovascular efficacy has been doubted over recent years. A series of randomized controlled trials (RCTs) addressing cardiovascular outcomes with DPP-4 inhibitors have been recently published, while previous meta-analyses failed to show any cardiovascular benefit with their use in patients with T2DM.

Purpose

The purpose of our analysis was to report the impact of antidiabetic treatment with DPP-4 inhibitors on different cardiovascular efficacy outcomes.

Methods

We searched PubMed for all published RCTs assessing cardiovascular outcomes after antidiabetic treatment with DPP-4 inhibitors. We extracted data related to the following efficacy outcomes: fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization and cardiovascular death.

Results

We pooled data from a total of 6 trials in a total of 52,520 patients. Antidiabetic treatment with DPP-4 inhibitors did not significantly affect any of the prespecified cardiovascular efficacy outcomes. More specifically, DPP-4 inhibitors compared to control led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction (RR=1.02, 95% CI: 0.94–1.11, I2=0%), hospitalization for heart failure (RR=1.09, 95% CI: 0.92–1.29, I2=65%) and cardiovascular death (RR=1.02, 95% CI: 0.93–1.11, I2=0%), as shown in figures 1a, 1c and 1f. In addition, DPP-4 inhibitors produced a non-significant decrease in the risk for fatal and non-fatal stroke (RR=0.96, 95% CI: 0.85–1.08, I2=0%) and coronary revascularization (RR=0.99, 95% CI: 0.90–1.09, I2=0%), as depicted in figures 1b and 1e. Finally, DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina (RR=1.00, 95% CI: 0.85–1.18, I2=0%), as shown in figure 1d.

Conclusions

Antidiabetic treatment with DPP-4 inhibitors does not seem to confer any significant cardiovascular benefit for patients with T2DM.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Influence of cardiovascular drugs on the efficacy and safety of dapagliflozin in patients with type 2 diabetes mellitus in the DECLARE-TIMI 58 trial
Authors: Oyama K , Raz I , Cahn A , Goodrich E , Bhatt D , Leiter L , McGuire D , Wilding J , Gause-Nilsson I , Mosenzon O , Sabatine M , Wiviott S
Published: October 2021

Background

In DECLARE-TIMI 58, the sodium glucose co-transporter 2 inhibitor (SGLT2i) dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in a broad range of patients with type 2 diabetes mellitus (T2DM). SGLT2i are known to have diuretic and anti-hypertensive effects. However, whether concomitant CV drugs influence the efficacy and safety of dapagliflozin in these populations is less well known.

Purpose

We examined whether dapagliflozin consistently reduced the risk of CV outcomes and whether the safety of dapagliflozin was similar with or without the concurrent use of various CV drugs.

Methods

DECLARE–TIMI 58 was a randomized trial of dapagliflozin versus placebo in patients with T2DM and either atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for CV disease followed for a median of 4.2 years. We stratified patients by the use of CV drugs at baseline commonly used for heart failure: angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers (ACEi/ARB), beta-blockers, diuretics, and mineralocorticoid receptor antagonists (MRA). Efficacy outcomes of interest were the composite of CV death/HHF and HHF alone. We used the Cox proportional-hazard model for these analyses.

Results

Of 17,160 patients, 13,950 (81%) used ACEi/ARB, 9,030 (53%) used beta-blockers, 6,967 (41%) used diuretics, and 762 (4%) used MRA at baseline. All were balanced by randomized treatment groups. Patients using CV drugs at baseline had a greater prevalence of atherosclerotic risk factors and established CV disease than those without. Dapagliflozin consistently reduced the risk of CV death/HHF regardless of the use of CV medications (Figure). For HHF alone, similar results were seen with no significant interactions for any of the classes. There were no significant treatment interactions by the concomitant use of any of CV drugs for adverse events including symptoms of volume depletion or acute kidney injury.

Conclusions

In this analysis from the DECLARE–TIMI 58 trial, dapagliflozin consistently reduced the risk of CV death/HHF and HHF alone irrespective of the concurrent use of various CV drugs without any treatment interaction for key safety events.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): The DECLARE–TIMI 58 trial was supported by AstraZeneca.
Frequency of antiplatelet therapy in coronary artery disease. Data from the disease management programme CAD
Authors: Hagen B , Griebenow R
Published: October 2021

Background

Physicians always aim to improve their patients' health and consequently also improve community health. Continued medical education (CME) should be designed to support this goal and thus not only provide knowledge transfer, but also influence clinical decision-making and close performance gaps. However, the relative weight of CME in this process needs to be determined.

Purpose

Main purpose of the study was to analyse APT prescription rates and differences between subgroups of patients in a disease management programme (DMP) for coronary artery disease (CAD).

Methods

In a retrospective study we analysed prescription rates for APT in 254,932 CAD patients (male: 64.4%), treated in a total of 3,405 practices in 2019 in a DMP in the region of North Rhine, Germany, to delineate the potential for change by CME to further improve community health. Analyses were run for the whole study population stratified by sex as well as for subgroups of patients suffering from myocardial infarction / acute coronary syndrome (MI/ACS), or who have been treated with percutaneous coronary intervention (PCI) or bypass surgery. Subgroup differences were analysed in a logistic regression model.

Results

Patients mean age was 72.7±11.2 years (mean ± 1SD), mean duration of DMP participation was 7.2±4.7 years and mean cumulative number of DMP visits was 27±17. APT prescription rates were 85.0% in male and 78.8% in female CAD patients. In subgroups of male CAD patients APT prescription rates were between 89.7% and 92.8%, in the same subgroups of female CAD patients the corresponding rates were between 87.8% and 92.0%. Rates for a missing APT prescription per practice were between 0.0044% and 0.0062% for male and female CAD patients respectively. Rates for a missing APT prescription per practice and DMP visit were 0.0002% for both sexes. In a multivariate model significant positive predictors of APT prescription were male sex (OR=1.37, 95% CI: 1.34–1.40), age ≥76 yrs (OR=1.11, 95% CI: 1.08–1.14), participation in DMP ≥4 and <10 yrs (OR=1.19, 95% CI: 1.16–1.22), MI/ACS (OR=1.14, 95% CI: 1.08–1.20), PCI (OR=1.97, 95% CI: 1.88–2.06) and bypass surgery (OR=1.14, 95% CI: 1.08–1.21).

Conclusion

Our study demonstrates that a multifaceted intervention, like a DMP, can achieve high attainment rates for APT in CAD. To describe the benchmark for CME to further improve attainment rates, consideration of absolute numbers of eligible patients per practice or physician is probably more appropriate than expression of performance as percentage values. This is especially true if attainment rates show substantial variations between subgroups, if subgroups show substantial variation in size, if attainment rates are already in the order of magnitude of 80% or higher, and if there are disparities in the evidence base underlying treatment recommendations related to subgroups.

Funding Acknowledgement

Type of funding sources: None.
Aspirin vs. P2Y12 inhibitors with anticoagulation therapy for atrial fibrillation: insights from the AFIRE trial
Authors: Fukaya H , Ako J , Yasuda S , Kaikita K , Akao M , Matoba T , Nakamura M , Miyauchi K , Hagiwara N , Kimura K , Hirayama A , Matsui K , Ogawa H ,   the AFIRE Investigators
Published: October 2021

Background

Patients with coronary artery disease (CAD) and atrial fibrillation (AF) can be treated with multiple antithrombotic therapies including antiplatelets and oral anticoagulants; however, this has the potential to increase bleeding risk.

Purpose

This sub-analysis aimed to evaluate the efficacy and safety of P2Y12 inhibitors and aspirin in patients also receiving oral anticoagulant therapy.

Methods

We evaluated patients from the Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial who received combination therapy (rivaroxaban plus a single antiplatelet agent). The choice of antiplatelets was left to the physician's discretion. The primary efficacy endpoint was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, and death from any cause. The primary safety endpoint was major bleeding according to the International Society on Thrombosis and Haemostasis criteria.

Results

A total of 1,075 patients were included (P2Y12 inhibitor group, n=297; aspirin group, n=778). Approximately 60% of patients were administered proton pump inhibitors (PPIs), and there was no significant difference in PPI use in the P2Y12 inhibitor and aspirin groups. Regarding the primary efficacy endpoint, there was no significant difference between the P2Y12 inhibitor and aspirin groups (hazard ratio, 1.31; 95% confidence interval, 0.88–1.94; p=0.178). Likewise, the primary safety endpoint was not different between the groups (hazard ratio, 0.79; 95% confidence interval, 0.43–1.47; p=0.456). In the detailed subgroup analysis, there were no differences in the efficacy and safety endpoints.

Conclusions

There were no significant differences between P2Y12 inhibitors and aspirin in cardiovascular events in patients with AF and stable CAD taking rivaroxaban in the chronic phase.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): The Japan Cardiovascular Research Foundation based on a contract with Bayer Yakuhin, Ltd. Summary of this study
Antiplatelet therapy and outcome in patients with COVID-19. Results from a multi-center international prospective registry (HOPE-COVID19)
Authors: Santoro F , Vitale E , Nunez Gil I , Guerra F , El-Battrawy I , Brunetti N D
Published: October 2021

Background

No standard therapy is currently recommended for Corona-virus-19 disease (COVID-19). Autopsy studies showed high prevalence of platelet-fibrin rich micro-thrombi in several organs. Aim of the study was to evaluate safety and efficacy of antiplatelet therapy (APT) in COVID-19 hospitalized patients and its impact on survival.

Methods

7824 consecutive patients with COVID-19 were enrolled in a multicenter-international prospective registry (HOPE-COVID19). Clinical data and in-hospital complications were recorded. AP regimen, including aspirin and other antiplatelet drugs, was obtained for each patient.

Results

During hospitalization 730 (9.3%) patients received AP drugs with single (93%, n=680) or dual APT (7%, n=50). Patients treated with APT were older (73±12 vs 62±17 years, p<0.01), more frequently male (70% vs 64%, p<0.01) and had higher prevalence of diabetes (39.5% vs 17%, p<0.01).

Patients treated with APT showed no differences in terms of in-hospital mortality (18% vs 19%, p=0.64, Log Rank p=0.23), need of invasive ventilation (8.7% vs 8.5%, p=0.88) and bleeding (2.1% vs 2.4%, p=0.43); However, after excluding patients treated only with anticoagulation, APT was associated with lower mortality rates (Log Rank p<0.01, relative risk 0.79, 95% CI 0.70–0.94) (Figure 1).

At multivariable analysis including age, gender, diabetes, hypertension, respiratory failure, pre-hospital therapy with antiplatelet drugs, in-hospital APT, and anticoagulation therapy, in-hospital APT was associated with a lower mortality risk (relative risk 0.29, 95% CI 0.22–0.38, p<0.001).

Conclusions

APT during hospitalization for COVID-19 could be associated with lower mortality risk without increased risk of bleeding. Randomized trials are needed to confirm these preliminary data.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Calcium channel blockers and beta-blockers could increased mortality of patients with COVID-19
Authors: Esteban-Lucia L , Zambrano Chacon M A , Venegas Rodriguez A M , Devesa-Arbiol A , Gonzalez-Rodriguez M , Maure-Blesa L , Avila-Barahona P , Pello-Lazaro A M , Gonzalez-Lorenzo O , Kallmeyer-Mayor A M , Fernandez-Roblas R , Villar-Alvarez F , Tunon J , Acena Navarro A , Franco-Pelaez J A
Published: October 2021

Background

High incidence of cardiovascular events has been described among patients with COVID-19 and since the beginning of the pandemic concerns have been expressed with medical treatments for cardiovascular disease, as they could contribute to the severity of illness in patients with COVID-19. We aim to analyze the effect of chronic treatment with calcium channel blockers and beta-blockers on COVID 19 severity in a Spanish cohort during the 2020 pandemic.

Methods

Observational study including all consecutive patients (≥40 years old) diagnosed with SARS-CoV-2 through PCR in the microbiology laboratory of our hospital, from March 2nd to 20th 2020. Clinical characteristics and drugs were recorded. The Primary end-point (PE) was all-cause death and the secondary end-point (SE) was the combined of death or the need for orotracheal intubation until 30 days of infection symptoms onset.

Results

We included 704 patients in our study. Baseline characteristics of the overall cohort can be seen in the table. Median age was 61 years old (IQR 52.9–72.9); 52.7% were female. 34.7% and 12.6% had hypertension and diabetes respectively. After a median follow-up of 111.5 days, 58 patients (8.2%) needed orotracheal intubation and 133 patients (18.9%) died. Secondary endpoint (all-cause death or need for orotracheal intubation) was reached by 164 patients (23.3%). The table described clinical differences between survivors and deceased patients.

After multivariate Cox modeling, age, male gender, diabetes, previous lung disease, BMI and the chronic intake of calcium channel blockers (HR 1.74, 95% CI (1.11–2.75), p=0.016) and beta-blockers (HR 1.71, 95% CI (1.07–2.76), p=0.026) were independently related with mortality. Other cardiovascular drugs (Antiplatelets, anticoagulants, diuretics, mineralcorticoid-receptor antagonists, angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors and statins) did not influence survival after SARS-CoV 2 infection (Figure).

The secondary outcome was reached by 164 patients (23.3%) and chronic treatment with calcium channel blockers remains as an independent predictor of mortality (HR 1.55, 95% CI (1.01–2.37), p=0.044).

Conclusions

Chronic treatment with calcium channel blockers and beta-blockers are independent predictors of mortality after SARS-CoV-2 infection. Further studies are needed to confirm these results.

Funding Acknowledgement

Type of funding sources: None. Description of studied populationOdds-ratio and CI for all-cause death
Factors related to hospital readmission of patients with acute coronary syndrome: a prospective cohort study
Authors: Lopes J , Russomanno L L R , Lopes C T L
Published: October 2021

Background

Hospital readmissions of patients with acute coronary syndrome (ACS) are frequent and associated with poor clinical outcomes and increased costs to the healthcare services. Identifying factors that might be associated with hospital readmission is important to support preventive interventions.

Purpose

To identify factors related to hospital readmission of patients with ACS.

Methods

A prospective cohort study. Patients hospitalized with ACS for the first time were included in the study. The outcome, hospital readmission for ACS, was assessed at 30 days, 6 months and 1 year after index discharge. Modifiable cardiovascular risk factors (arterial hypertension, dyslipidemia, diabetes mellitus, smoking, degree of addiction to smoking, use of alcohol, physical inactivity, obesity, stress, depression, excessive daytime sleepiness, obstructive sleep apnea syndrome, hormone replacement) and non-modifiable risk factors (age, race, family history of coronary heart disease) were evaluated as potential predictors of the outcome. Other variables that might have contributed to readmission were also included: marital status, family income, occupation, education, adherence to medication and type of treatment (clinical, percutaneous coronary intervention or coronary artery bypass grafting). The association between hospital readmission and potential predictors was assessed using the Log-Rank test and Cox's simple regression model. Factors whose associations had a p-value of less than 0.20 in the simple regression and other variables of clinical interest were evaluated in a Cox multiple regression model, with p<0.05 considered significant. The study was approved by two Research Ethics Committees.

Results

216 patients were included and the incidence of readmission was 15.7%. Most of the patients were male, white, married, had an income between two and four minimum wages, and a mean age of 60 years. Half of the patients had high adherence to medication. The cardiovascular risk factors identified in most patients were sedentary lifestyle (79.6%), arterial hypertension (63.4%) and obstructive sleep apnea (51.9%). The only independent predictor for readmission was surgical treatment (p=0.026).

Conclusions

Participants had several cardiovascular risk factors and the predictor of hospital readmission was surgical treatment. Identifying the predictive factors of a given population helps nurses in planning and guiding hospital discharge.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Conselho Nacional de Desenvolvimento Científico e Tecnolόgico (CNPq)
The needs of older persons undergoing heart surgery: unveiling a nursing intervention through focus groups
Authors: Nicola Rodrigues S , Rafael Henriques H , Henriques M A
Published: October 2021

Background

The progressive ageing of the population, the prevalence of chronic diseases, such as cardiovascular diseases and heart disease with surgical indication, have a significant expression, either with a curative objective or to increase quality of life. Waiting for surgery is often a period of anxiety and fear. Preoperative waiting time can be used to better prepare these patients for surgery.

Purpose

The purpose of this research was to identify the needs of older people waiting for heart surgery.

Methods

A qualitative exploratory approach was used to gain an understanding of the participants' perception of what are the needs of older persons waiting for heart surgery. Focus Groups were used to collect information. Three interviews were conducted with: a group of nurses with experience in cardiothoracic care, individuals submitted to heart surgery (≥65 years) and individuals waiting for heart surgery (≥65 years); enrolling up to 17 participants from October 2019 to January 2020. Qualitative data analysis was conducted using the interactive model, at first similar data chunks were categorized by codes, allowing further analysis of data. Condensing data enabled us to retrieve the most significant material, further condensing it into smaller number of categories. The MaxQDA software, and EQUATOR COREQ guidelines were followed.

Results

Three categories emerged: (i) Information focused on facilitating health promotion and self-care, information regarding the hospital stay and granting access to information; (ii) Emotional support described patient's feelings towards the upcoming surgery and the need to keep them calm, involving their families and caregivers; (iii) Access to care, patients should be kept involved and engaged in managing self-care.

Conclusion

A preoperative intervention is necessary to support older persons waiting for heart surgery and the education provided should be focused on patients' needs. Caring for individuals awaiting heart surgery may be challenging due to the barriers imposed by physical distance and emotional distress. The identified needs of individuals awaiting heart surgery allow health professionals to deepen their knowledge regarding the patient's care.

Funding Acknowledgement

Type of funding sources: None. Listing of categories and sub-categories
Deep learning for automated left ventricular outflow tract diameter measurements in 2D echocardiography
Authors: Zha S Z , Rogstadkjernet M , Klaeboe L G , Skulstad H , Edvardsen T , Samset E , Brekke P H
Published: October 2021

Background

Left ventricular outflow tract diameter (LVOTd) is routinely measured to calculate stroke volume and estimate aortic valve area by the continuity equation. Despite LVOTd being regularly measured clinically, significant inter- and intraobserver variability is evident. This variability is highly impactful on both aortic stenosis evaluation and cardiac output calculation due to the squaring of the LVOT radius.

Purpose

We aimed to investigate if LVOTd measurements from clinical echocardiographic examinations could be used in a deep learning (DL) model to automatically perform LVOTd measurements with equivalent accuracy and improved consistency compared to current practice.

Methods

Data was collected from clinical echocardiographic examinations performed on 656 consecutive patients admitted to the cardiac catheterization laboratory at a university hospital in January – December 2018. Parasternal views with cardiologist annotated LVOTd coordinates were assessed for 1314 echocardiographic still images. The quality of the still image and annotated LVOT ground truth were individually graded as high, medium and low by experienced cardiologists to establish a rigorous training basis. Spatial geometry data was preserved for each still image in order to distinguish between different degrees of image zoom. Data was randomly split into training, validation and testing sets (68%, 17%, 15%). A fully convolutional network based on the Resnet50 architecture was used with a custom loss function with heatmap regression. Image augmentations were added to extend the dataset.

Results

When including echocardiographic images of any quality (n=1314) in the model training and inference, the median absolute difference between cardiologist LVOTd and DL LVOTd was 0.97 mm (95% Confidence interval (CI) 0.79–1.14). Using only high and medium quality still images and ground truth (n=869) in the training and inference, median absolute difference decreased to 0.81 mm (95% CI 0.60–0.96). Adding image augmentations to this dataset further improved the model, resulting in a median LVOTd absolute difference of 0.66 mm (95% CI 0.51–0.78). The LVOTd error in inference increased with decreasing image quality, as shown in Figure 1, with two predictions (0.9%) failing completely.

Conclusion

Deep learning models are capable of measuring LVOTd with comparable accuracy to cardiologists when trained on clinical data. Data quality affects both training and inference. Even with a slightly lower accuracy when used on lower quality echocardiographic images, DL-assisted LVOT measurement has a clear potential to increase repeatability and consistency of LVOTd measurements.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Research Council of Norway (Norges forskningsråd) Figure 1
Multicentre validation of point-of-care screening tool for heart failure: single-lead ECG recorded by smart stethoscope predicts low ejection fraction using artificial intelligence
Authors: Bachtiger P , Scott F , Park S , Petri C , Padam P S , Sahemey H , Dumea B , Ribeiro M , Alquero R , Bual N , Cheung W S , Rana B , Keene D , Plymen C M , Peters N S
Published: October 2021

Background/Introduction

Artificial intelligence (AI) applied to 12-lead ECG can identify left ventricular ejection fraction (EF) ≤35% with a sensitivity and specificity of 86.3% and 85.7%, respectively. Whether AI algorithms trained on 12-lead can accurately predict EF from single-lead ECGs (recorded by a smart stethoscope) remains unknown. This could facilitate point-of-care screening for low EF during routine clinical examination.

Purpose

First independent multicentre real-world UK National Health Service (NHS) prospective validation of 12-lead-ECG-trained AI algorithm applied to single-lead ECG recorded by a smart stethoscope, with AI algorithm tuned to detect EF ≤40%.

Methods

Prospective recruitment of unselected patients attending for echocardiography across six urban NHS hospital sites (UK). In addition to transthoracic echocardiogram (routine care), all participants had 15 seconds of supine, single-lead ECG recorded at six different positions (figure), encompassing standard anatomical positions for cardiac auscultation. A convolutional neural network (CNN) previously trained on 35,970 independent pairings of 12-lead-ECG and echocardiograms was retrained to use the single-lead ECG as input. Accuracy of CNN detection of low EF (binary ≤40%) is reported at a threshold of 0.5 against gold-standard; echo-determined percentage EF.

Results

Among 353 patients recruited (mean age 63±17; 58% male, 43.1% non-white), 309 (87.5%) had an EF >40%, and 44 (12.5%) had EF ≤40%. The best single recording position in isolation was position 3 (sensitivity 57.9% [42.2–73.6], specificity 86.3% [82.2–90.3]). Taking any of the six positions performed during the examination as predicting EF ≤40%, this achieved a sensitivity of 81.2% and specificity of 61.5%.

Conclusion(s)

In this first prospective multicentre validation study the retrained AI algorithm reliably detected low EF from single-lead ECGs acquired using a novel ECG-enabled stethoscope in standard auscultation positions. The ability to identify patients with possible low EF during routine physical examination addresses a significant unmet clinical need in point-of-care ruling in/out of heart failure, and has potential to provide broader population-level screening for asymptomatic cardiovascular disease.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research, Accelerated Access Collaborative & NHSX: Artificial Intelligence in Health & Social Care Award
Utility of device-derived daily activity, a novel digital biomarker, to predict ventricular arrhythmias – data from the CERTITUDE registry
Authors: Kutyifa V , Rosero S , Harrel C , Singh J , Hicks J , Chinitz L , Varma N , Piccini J , Turakhia M
Published: October 2021

Background

While there have been prior studies showing an association between activity and outcomes, there have been no studies examining the temporal relationship between device-derived daily activity, a novel digital biomarker, and ventricular tachyarrhythmias (VT).

Purpose

In a big dataset with over 55,000 pacemaker, ICD, and CRT devices, we aimed to identify whether changes in activity predict VT, or else VT predict changes in activity.

Methods

The CERTITUDE registry comprises a de-identified database of over 55,000 U.S. BIOTRONIK pacemaker, ICD, CRT devices, and loop recorders active on Home Monitoring®. Daily data on leads, arrhythmias, and physiological parameters such as activity are captured. Patient activity is reported daily as percentage active during the day, assessed by a one-axis accelerometer at ∼0.4 Hz frequency. Analysis to ascertain temporal changes in device-derived activity associated with treated VT was performed using the first event per device and 7-day activity windows (baseline, pre- and post-event). Baseline period was defined as 31–38 days prior to VT. VT events were categorized by heart rate (≤200 bpm,>200 bpm) and treatment (shock with or without ATP, ATP alone). Differences in activity between baseline, and pre- and post-VT were analyzed using the binomial proportion test.

Results

A total of 16,475 devices (9732 ICDs, 6743 CRT-Ds) had activity data available for analysis. The cumulative follow-up duration was 18,355 years (5.6 million days with transmission). Of the 2636 VT events analyzed, 1409 had a heart rate >200 bpm, and 593 were treated with shock. Patients with VT events >200 bpm treated with shock had a significant reduction in activity post-VT with a median −8.7% reduction (IQR −24.6%; 7.3%, p<0.001). However, there was no reduction in activity before the VT>200 bpm (p=0.690) (Figure). VT events >200 bpm treated with ATP alone were not associated with reduction in activity before or after the episode. Similarly, VT events ≤200 bpm treated with shock were also associated with a reduction in activity following the event (−5.8%, IQR −29.5, 12.3%, p=0.003), but not prior to the VT event.

Conclusions

In this report from the CERTITUDE registry, we have shown a temporal decline in device-derived activity following ventricular arrhythmias>200 bpm and ≤200 bpm treated with a shock, but not in patients treated with ATP. Monitoring device-derived activity post-VT events with a shock could provide relevant clinical information and potentially warrant intensified treatment.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Biotronik