bluuebunny/crossref_metadata_2025_split huggingface dataset:
New onset atrial fibrillation and heart failure among patients with multiple myeloma: analysis from a nationwide french medical information database
Authors: Cottin Y , Boulin M , Doisy C , Mounier M , Caillot D , Chretien M L , Bodin A , Herbert J , Bonnotte B , Zeller M , Maynadie M , Fauchier L 
Published: October 2021

Abstract

Background
Over the last decade, new therapies, screening optimization, and cardiovascular management have changed the cardiovascular prognosis of patients with multiple myeloma (MM). Older studies suggested that MM could be associated with increased risk of heart failure (HF). Based on a nationwide hospitalization database, we aimed to assess the risk of hospitalization for Heart failure (HF) and/or Atrial fibrillation (AF).

Methods
From 1st January 2013 to 31st December 2013, 3,381,472 adults (age ≥18 years) were hospitalized for any reason in French hospitals and then had at least 5 years of complete follow-up (or suffered death earlier). We identified 15,774 patients diagnosed with known MM at baseline. The outcome analysis on hospitalization for new onset HF or AF was performed with follow-up (FU) starting at the time of last event. For each patient with MM, a propensity score-matched patient with no MM was selected (1:1) using the one-to-one nearest neighbor method (n=15774 in each group).

Findings
In the propensity-score-matched population, mean±SD FU was 3.7±2.3 years, median (IQR)5.0 (1.3–5.7) years, mean age was 71±12y, and most were female (55%). When compared with patients without MM, MM patients were more likely to have history of HF (16.8% vs. 10.5%, p&lt;0.0001), pulmonary edema (1.5 vs. 0.8%, p&lt;0.0001), or AF (13.4% vs. 9.6%, p&lt;0.0001). At FU, MM patients had a higher risk of all-death (yearly rate 20.02 vs 11.39%/year). Moreover, yearly rates of new onset HF or AF, which were the common CV causes of re-hospitalisation, were higher in the MM group, i.e. respectively for incidence rate, 7.47 vs 5.42%/year (p&lt;0.0001) and 4.57 vs 3.72%/year (p&lt;0.0001). Multivariate analysis showed that MM remained significantly associated with a higher rate of HF and AF (HR (95% CI): 1.343 (1.276–1.413) and 1.196 (1.128–1.269), respectively). Results were similar in sensitivity analysis limited to patients with recent MM (i.e. diagnosed within the 3 previous months).

Interpretation
From a large nationwide hospitalization database, we show that patients with MM had a higher risk of new onset HF and AF. Our findings highlight the key issue of cardiovascular management in patients with MM.

Funding Acknowledgement
Type of funding sources: None.
Is early percutaneous coronary intervention safe in patients ACS and cancer?
Authors: Scarpone M , Bergami M , Cenko E , Vasiljevic Z , Zdravkovic M , Vavlukis M , Kedev S , Milicic D , Manfrini O , Bugiardini R 
Published: October 2021

Abstract

Background
Patients with malignancies may have a high pro-thrombotic status as well as a high risk of hemorrhagic events either due to the tumor or its treatment. For this reason, these patients have always been excluded from randomized clinical trial on percutaneous coronary intervention (PCI).

Aim
To investigate the safety of PCI in patients with malignancies admitted for an AMI.

Methods and results
Retrospective analysis on an international European ACS registry. Primary endpoint: in-hospital mortality. Secondary endpoint: periprocedural-complications. There were 273 patients (35% women) with AMI and malignancies. Colon (19%), prostate (14%), breast (13%), lung (8%) and blood (8%) malignancies were the most frequents type of cancer. Women and men had similar age (68±11.5 vs 69.1±11.5, p=ns). STEMI was in 56% of patients (with no significant gender difference: 51% men vs 65% women, p=0.09). PCI was performed in 64% of patients (with primary PCI in 75% of STEMI). The rate of complications during cardiac catheterization and intervention was 6.5% (2.1% distal embolization, 2.1% no-reflow, 0.7% acute closure, 0.7% dissection, 0.7% perforation, none major bleeding). Nobody among patients that had cardiac catheterization and intervention complications died during hospital stay. In-hospital mortality was 5.9%. The group of patients treated with PCI had a significantly lower rate of death then that of those treated non invasively (1.7% vs 13.1%, p&lt;0.ehab724.28851). Factors associated with lower probability to receive cardiac catheterization were older age (OR: 0.94, 95% CI: 0.92–0.97) and absence of typical chest pain at admission (OR: 0.38; 95% CI: 0.18–0.81), but the type of malignancy and gender were not. On multivariable model, age (OR: 1.1, 95% CI: 1.03–1.17) and PCI (OR: 0.16, 95% CI: 0.04–0.59) were independently associated with the risk of in-hospital death for ACS (increased and decreased risk, respectively).

Conclusion
These preliminary data from real word support the safety use of PCI in patients with malignancies and ACS, which have always been excluded from randomized clinical trial.

Funding Acknowledgement
Type of funding sources: None.
Incidence of maternal and fetal complications in pregnant with mechanical prosthetic cardiac valves: a cohort study
Authors: Youssef G , Hosny M , Ramadan W , Baligh E 
Published: October 2021

Abstract

Background
In developing countries, an unusually large number of women of childbearing age have mechanical valves because rheumatic fever and concomitant valvular heart disease are still common and most severely affect the young. Managing anticoagulation during pregnancy is challenging, and the rate of complications is relatively high.

Purpose
The aim of this study was to detect the incidence of maternal and fetal complications in pregnant women with prosthetic valve in a high-risk pregnancy unit in one of the developing countries.

Methods
This study included 106 pregnant women with prosthetic heart valves on oral anticoagulant therapy. Excluded from the study were patients with low ejection fraction (&lt;50%), patients with other comorbidities that may affect the pregnancy outcomes and patients who were not willing to share their data. Patients were followed up since presentation to the high-risk pregnancy unit till delivery. At each visit, women were clinically assessed for the occurrence of complications (heart failure, infective endocarditis, prosthetic valve dysfunction, systemic emboli, new onset arrhythmia, antepartum hemorrhage, or death). Babies were evaluated by an Obstetrician for intrauterine growth retardation or fetal death, abortion, oligo or polyhydramnios, and congenital heart diseases.

Results
The mean age was 28.5±4.2 years, 58 patients (54.7%) had mitral valve prothesis, 34 (32.1%) had aortic valve prosthesis and 14 patients (13.2%) had double valve prothesis. Fifty-three patients (50%) received warfarin throughout pregnancy and the rest switched to heparin in the first trimester. Cerebrovascular stroke occurred in 4 patients (3.8%), all were on the 1st trimester and all were taking heparins. The mean gestational age at delivery was 36.2±4.8 weeks and the mean fetal birth weight was 2435±791.5 gm. Thirty-three abortions were reported and the mean gestational age for abortion was 13 weeks±6 days while the mean gestational age for intrauterine fetal death was 29±4 weeks, table. Two babies had congenital heart diseases (ventricular septal defect and patent ductus arteriosus) and in both, the mothers were taking warfarin &gt;5 mg/day during the second and third trimesters.

Conclusion
In this tertiary care centre, the incidence of maternal complications was relatively small while the incidence of fetal complications was high, especially in mothers taking higher warfarin doses. Switching to heparin in the first trimester increased the risk of systemic embolization.

Funding Acknowledgement
Type of funding sources: None.
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

Abstract

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&lt;0.05), circulating adhesion molecules (ICAM-1 and VCAM-1, p&lt;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

Abstract

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) &lt;1.7 cm or pulsed Doppler peak annular velocity (S') &lt;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 &lt;17mm and/or S'&lt;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 &lt;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

Abstract

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&lt;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&lt;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

Abstract

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 &gt;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 &gt;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 &lt;70 mg/dL and in 12 patients (46%) LDL-C was &lt;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

Abstract

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&lt;0.001), with significant individual reductions in acute coronary (HR 0.83; 95% CI 0.75–0.91; P&lt;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.