bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic versus prophylactic anticoagulation in patients with COVID-19: a meta-analysis of randomised controlled trials
Authors: Sakurai R
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Background

Several systematic reviews and meta-analyses have been conducted to evaluate the effects of anticoagulation on patients admitted with coronavirus infectious disease 2019 (COVID-19). However, since most of them consist of observational studies, the optimal dose still remains controversial.

Purpose

The purpose of this study was to investigate the efficacy and safety of therapeutic anticoagulation compared with prophylactic anticoagulation in patients admitted with COVID-19.

Methods

A meta-analysis was conducted on randomised controlled trials (RCTs) to minimise bias. PubMed and the Cochrane Central Register of Controlled Trials were queried for the terms "covid-19," "(anticoagulation OR thromboprophylaxis)," and "randomised." The same terms or relevant studies were also queried on the website of the ClinicalTrials.gov and relevant reviews. The clinical endpoints of interest were all-cause death, thromboembolism, and major bleeding. Pooled estimates were calculated using a random-effects model.

Results

A total of 7 RCTs were included in this study. The risk of thromboembolism was lower (odds ratio (OR) 0.54; 95% confidence interval (CI) 0.41-0.73; p < 0.001) and the risk of major bleeding was higher (OR 1.87; 95% CI 1.21-2.90; p = 0.005) in the therapeutic anticoagulation group than in the prophylactic anticoagulation group. On the other hand, the risk of all-cause death was similar (OR 0.92; 95% CI 0.65-1.31; p = 0.65) between the 2 groups. In a subgroup analysis, the risk of thromboembolism was also lower in the therapeutic anticoagulation group compared with the prophylactic anticoagulation group both in moderately and severely ill patients, respectively. However, the risk of major bleeding was more likely to higher (OR 1.85; 95% CI 0.98-3.49; p = 0.06) in the therapeutic anticoagulation group than the prophylactic anticoagulation group only in severely ill patients.

Conclusions

Therapeutic anticoagulation is associated with a lower risk of thromboembolism and a higher risk of major bleeding compared to prophylactic anticoagulation in patients hospitalised with COVID-19. Therapeutic anticoagulation may be more beneficial for moderately ill patients.
Association between inflammatory biomarkers and 30-day mortality in patients with acute myocardial infarction complicated by cardiogenic shock
Authors: Bo Kunkel J , Josiassen J , Helgestad O K , Schmidt H , Holmvang L , Okkels Jensen L , Berg Ravn H , Eifer Moeller J , Hassager C
Published: May 2022

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): Hjertecentrets Forskningsudvalg, Rigshospitalet

Background

Cardiogenic shock often induces an inflammatory response, but the prognostic importance of this is not well studied.

Purpose

The present study investigates whether the inflammatory response as reflected in routine blood samples taken during admission is associated with 30-day mortality in patients with cardiogenic shock due to acute myocardial infarction (AMICS). We assessed patients surviving 2 days, since a full CRP-response may take more than 48 hours to develop.

Methods

Consecutive patients (N=1716) with a validated diagnosis of AMICS admitted to one of two tertiary heart centres covering a base population of approximately 4 million in the period from 2010 to 2017 were included. The median values of total leucocyte count (WBC) and C-reactive protein (CRP) corresponded well to optimum thresholds found using ROC analysis and were used as cut-off for stratification.

Results

A total of 1114 (1122) of the 1716 patients were alive and had WBC (CRP) measured at day 3.

Median WBC was 12.6 x 109/L. Median CRP was 146 mg/L.

Patients with an elevated leucocyte response were significantly older (66 vs 64 yrs, P<.001), had a higher prevalence of diabetes mellitus (18% vs 13%) and were admitted with lower left ventricular ejection fraction (LVEF) (P<.001). Less had suffered out-of-hospital cardiac arrest (44% vs 58%, P<.001) or underwent mechanical ventilation during admission (84% vs 91%, P<.001).

Patients with an elevated CRP had higher Body Mass Indexes (BMI 27 vs 26, P=.03) and were admitted with higher lactates (6.4 vs 5.7 mmol/L, P=.01) and a lower EF (P=.05), while more underwent mechanical ventilation during admission (92% vs 82%, P<.001).

Elevated WBC among patients alive at day 3 was associated with a significantly higher 30-day mortality rate of 43% vs 30%, Plogrank<.001. Patients with an elevated CRP had a mortality rate of 42% vs 29%, Plogrank<.001. (fig. 1,2)

In a multivariable model for each biomarker, adjusting for factors associated with mortality in AMICS, including age, sex, diabetes, stroke, out-of-hospital cardiac arrest, arterial lactate, LVEF and mechanical ventilation, an elevated inflammatory response remained significantly associated with mortality. (HR(WBC↑) = 1.63 [1.29;2.06], P<.001. HR(CRP↑) = 1.51 [1.21;1.90], P<.001).

Conclusions

Leucocyte and CRP response at day 3 of admission are associated with increased mortality in AMICS.
Safety and effectiveness of angiotensin receptor-neprilysin inhibitors in patients with heart failure with preserved ejection fraction (ARNI-PRESERVED study)
Authors: Jariwala PVJ , Jadhav KARTIK , Khetan SS
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Background

The goal of this study is to look at the safety and efficacy of ARNI (valsartan/sacubitril), a combination of angiotensin II receptor blocker and neprilysin inhibitor (ARNI), in patients with heart failure with preserved ejection fraction (HFpEF).

Purpose

ARNI decreases the hazard of cardiovascular death and hospitalization in patients with chronic HFrEF (NYHA Class II–IV). Although there are several evidence based therapies for HFrEF, there is no effective therapy for HFpEF at the presently. In Paragon-HF trial, ARNI demonstrated a minimal evidence of additional improvements in patients with HFpEF

Material and methods

A retrospective research with a clinical population was carried out. A total of 154 HFpEF patients (87 females and 67 males) were treated with ARNI, which was subsequently titrated up to a maximum tolerable dose and monitored in an outpatient clinic. 56 patients were given ARNI while in the hospital for decompensated heart failure before being discharged.

Results

Patients were categorized as New York Heart Association (NYHA) class III (71.4%) and NYHA class II (28.6%). Diabetes mellitus was identified in 52% of patients, while hypertension was found in 78%. Symptomatic clinical improvement was observed, with a substantial decrease in NYHA class down to NYHA class II (p=0.018). A considerable decrease in NYHA class resulted in symptomatic clinical improvement as well as the rales and peripheral oedema had resolved (p<0.001). The NT-pro-BNP levels were considerably lowered (p<0.001). The echocardiographic parameters for diastolic function (E/A, E/E’ ratios) improved. In individuals with HFpEF, ARNI resulted in significant clinical benefits (Table -1).

Conclusion

In individuals with HFpEF, sacubitril/valsartan, ARNI resulted in significant clinical benefits A randomized research is also required to see if it results in beneficial outcomes for a wider sample.
Indications, outcomes and complications after ECMO implantation in the cath lab - a single-center retrospective study
Authors: Kralicek S , Meier CS , Distelmaier K , Niessner A , Heinz G , Lang IM , Hengstenberg C , Krychtiuk KA , Speidl WS
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Background

Despite the increase of extracorporeal membrane oxygenation (ECMO) employment around the globe over the last decades, studies describing the emergency use of venoarterial (VA)-ECMO in the cardiac catheterization laboratory (CCL) are scarce.

Purpose

The aim of this study was to describe the patient population that received ECMO in the CCL of a tertiary care center and the associated complications and outcomes.

Methods

In this single-center retrospective study we reviewed the baseline clinical and laboratory characteristics, indications and outcomes of adult patients, who received VA-ECMO between 2011 and 2019.

Results

In the given time period, ECMO use in the CCL increased drastically. Mean age of the 83 patients was 58.3 ± 12.5 years, 78.3% were male. From 2011 to 2018 ECMO-use in the CCL increased drastically. The most common indication for ECMO implantation was cardiac arrest (66%), followed by cardiogenic shock (12%), high-risk PCI (11%), and procedure-related complications (10%). While 30-day mortality in the total study population was 69%, it varied greatly depending on the underlying indication for ECMO therapy (cardiac arrest 78%, cardiogenic shock 20%, high-risk PCI 44%, procedure-related complications 88%). The most commonly occurring complications were acute kidney injury (20%) and cannula site bleeding (20%), followed by extremity complications (19%), sepsis (18%), major bleeding (10%) and stroke (8%). Of interest, patients receiving ECMO therapy after in-hospital cardiac arrest showed greater survival rates (28.2%) as compared to patients after out of hospital cardiac arrest (18.2%; p=0.045). High serum lactate levels (p=0.018) and low baseline pH values (p=0.001) at baseline were associated with a significantly increased 30-day mortality after ECMO implantation.

Conclusion

The emergency use of VA-ECMO in the CCL increased over the last years and was associated with a high 30-day mortality in our study population. Still, a >20% survival rate in the group of patients with refractory cardiac arrest, an otherwise futile situation, suggests that VA-ECMO implantation is reasonable in selected patients. As high admission serum lactate levels and the baseline pH are strong predictors of outcome, such parameters may be used to guide decision making.
Experience with zotarolimus eluting stent in left main percutaneous coronary intervention at a very long-term follow-up
Authors: Sanchez Perez I , Concepcion Suarez R , Gonzalvez Garcia A , Freites Esteves A , Martinez Del Rio J , Moron Alguacil A , Munoz Garcia M , Negreira Caamano M , Aguila Gordo D , Mateo Gomez C , Soto Perez M , Cubides Novoa AF , Rayo Gutierrez M , Lozano Ruiz Poveda F
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Introduction

Drug eluting stents (DES) has improved the results of percutaneous coronary intervention (PCI) in terms of safety and effectiveness in left main coronary artery (LMCA) disease. Zotarolimus is a second-generation drug with excellent clinical outcomes but nowadays their results are unclear in this subgroup of high-risk coronary lesions.

Purpose

The main objective of this study was to evaluate the efficacy and safety of zotarolimus eluting stent (ZES) in LMCA disease at 14-year follow-up.

Methods

We prospectively included 432 consecutive patients (69 ± 12 years, 75.5% male) with LMCA disease treated with PCI and ZES between June 2006 and June 2020. We evaluated the presence of major adverse cardiovascular events (MACE) defined as cardiac death, nonfatal myocardial infarction, target lesion revascularization (TLR) and stent thrombosis, after 14-year clinical follow-up (median 61 months).

Results

52.8% of patients had stable coronary disease and 47.2% acute coronary syndrome (38.2% Non-STEMI and 9% STEMI). 40.7% were diabetic patients and 40.8% presented moderate-severe left ventricular systolic dysfunction. 5.8% were protected LMCA and 81.7% bifurcated lesions. An intra-aortic balloon pump was needed in 4.9% of the cases. Mean logistic EuroSCORE was 6.7% and Syntax score was ≥ 23 in 73.1% of patients. The most frequently bifurcation technique employed in LMCA was "provisional stenting" in 67.1% of cases with an angiographic success of 99.3%. Complication rate in the procedure was 4.6% with one intraoperative death. During follow-up, MACE rate at 14 years was 17.4% (12.5% cardiac death, 3.5% nonfatal myocardial infarction, 4.2% TLR and thrombosis rate 0.5%). We observed significant differences in the occurrence of MACE in diabetic patients (p=0.002), chronic kidney insufficiency (p<0.001), severe left ventricular systolic dysfunction (p<0.001) and patients in which we didn´t perform final kissing balloon (p=0.03). 21.07% of patients had an angiographic follow-up.

Conclusions

PCI treatment with ZES in LMCA disease is safe and effective with a low rate of immediate complications and a low rate of mayor cardiac events at very long-term follow-up. Patients with diabetes mellitus or chronic kidney insifficiency, severe left ventrcular systolic dysfinction or those in wich didn´t performe a final kissing balloon have worse prognosis.
Application of artificial intelligence to optimize the diagnosis and treatment of acute coronary syndrome: a real experience
Authors: Mota D , Kuster GW , Orletti D , Souza BF , Silva MA , Paiva LAPA , Burgard C , Candoti MW , Silva JHL
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Background/Introduction

cardiovascular disease (CVD) is the leading cause of death in the world, with acute myocardial infarction (AMI) being the main responsible for this leadership. One of the determining factors in the outcome of Acute Coronary Syndrome (ACS) is the time to start treatment. An extremely promising path for obtaining earlier diagnosis and treatment has been the use of technological innovations in emergency care units.

Prupose

this study was carried out to assess the impact of applying a technology hub in the chest pain scenario in the emergency room, regarding the feasibility and potential reduction of time for diagnosis and treatment of ACS.

Methods

data obtained from 10 hospitals in the public health system in Brazil, which implemented the technology hub in the last 7 months (May to October 2021), were analyzed. This technology hub uses Artificial Intelligence (AI) to identify electrocardiograms (ECGs) with a high probability of alterations, which must be reported within 5 minutes by the cardiologist on shift (24/7) on the platform.

Results

5,506 ECGs were entered into the platform, of which 53.77% (2,961) were considered abnormal; of these, 9.92% (294) had alterations compatible with ischemic events (currents of injury or myocardial ischemia). The median time for the ECG report made by the specialist was 2 minutes and 51 seconds.

Conclusion

the implementation of a technology hub in the chest pain scenario in the emergency room proved to be feasible and has great potential for reducing the distance between symptoms and the treatment of patients with ACS.
Unstable angina in the context of high sensitive troponins: still a marker of high risk? A comparison of outcomes with adjudicated type 1 myocardial infarction
Authors: Dakshi A , Ihsan J , Khand A
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Background

Unstable angina (UA), considered historically a marker of high risk, has rarely been studied in the high sensitive troponin era. We sought to characterise this population and determine short and medium term outcomes for UA who did not have elevated high sensitive troponins and compared this to adjudicated type 1 MI and the global population of suspected ACS.

Method

We conducted a post-hoc analysis of 2 prospective cohort studies of suspected acute coronary syndrome in 2 hospitals in the northwest of England. (n=3018) We used a symptom scoring system to diagnose unstable angina. Type 1 MI was diagnosed by blinded, independent physician adjudication according to 3rd universal criteria for MI. Follow-up was 100% complete for all patients to 1 year.

Results

185 and 259 were adjudicated as suffering from UA and NSTEMI respectively. We restricted our analysis to 158 patients with UA with high sensitive troponin T (Roche elecsys) ≤14ng/l (≤99th percentile). Compared to NSTEMI population UA cohort were younger (59 vs 74, p<0.002), had a lower incidence of hypertension (56% vs 69%, p= 0.009), had lower risk scores (TIMI 2 vs 3, p=0.001, GRACE 97.5 vs 140, p<0.0001, HEART 4 vs 7, p<0.0001) and had lesser ECG abnormalities ( ST depression >1mm, 5% vs 15.6%, p=0.001, T wave flattened, biphasic or inverted 24% vs 47.8%, p<0.0001).

Type 1 MI to 30 days and 1 year in the UA cohort was 1.9% and 3.1% respectively compared to a repeat type 1 MI in the NSTEMI cohort of 0.8% and 2.4% respectively. Only 1 (0.8%) all cause death was recorded within one year in the unstable angina cohort as opposed to 36 (14.4%) in the NSTEMI group. Revascularisation rates were unsurprisingly lower in the UA cohort to 30 days compared to NSTEMI cohort (table 1)

Conclusion

Unstable angina, in the high sensitive troponin era is associated with a small early and medium term risk of myocardial infarction. Risk of medium-term MACE is much lower compared to patients with confirmed type 1 myocardial infarction.
Optimal solution for coronary bifurcation lesions, a comparison between bioresorbable scaffolds and dedicated bifurcation stents
Authors: Alsinbili A
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Introduction

Coronary bifurcation lesions (CBL) constitute 15-20% of all coronary lesions and they constitute a challenge both technically and prognostically.(1) Bioresorbable scaffolds (BRS) represent a novel invention in the realm of coronary stenting.(2) They have a degradable structure that survives for 12-24 months,(3) allowing enough time for re-endothelialisation while they gradually disappear leaving the artery geometrically intact. The use of BRS is potentially beneficial in the treatment of CBLs because of these lesions’ complex geometry.(4)

Purpose

The aim of this study was to assess the effectiveness and safety of BRS in CBL when compared to dedicated bifurcation stents (DBS) by comparing the 12-months clinical outcomes including rates of cardiac death (CD), myocardial infarction (MI), target lesion revascularisation (TLR), and stent thrombosis (ST).

Methods

This study was conducted using PRISMA guidelines (figure 1). (5) a systematic literature review was made by searching ScienceDirect, EMBASE, MEDLINE, NIH, TRIP database, PUBMED, and ClinicalTrials.gov. Eligibility criteria included studies published since 2013 in English language. They must be designed to study bifurcation lesions and reporting clinical outcomes rather than procedural results. Studies must have either studied BRS or DBS. Risk of bias was assessed through a combined score consisting of MINORS and modified Cowley’s criteria. (6) Qualitative synthesis of results is performed through Microsoft Excel 365. Tests of heterogeneity were conducted using Q statistic, and between-study heterogeneity was assessed with the I2 statistic; also, publication bias was investigated graphically using funnel plots.(7) Meta-analysis was performed using the "meta" package in R software application.

Results

14 studies were included with 1742 participants: eight studies of BRS (n=1038) and six studies for DBS (n=704), with an average follow-up period of 12 months. The mean age of participants was 60 years for the BRS arm and 65.6 years for DBS arm (p-value < 0.001). Almost 80% of participants are male (p-value= 0.148) and around two-thirds who are smokers or suffer from hypercholesterolemia (p-value: 0.202, 0.094 respectively) (Figure-2). There were six cardiac deaths in the BRS group compared to seven CDs in the DBS group (p-value = 0.56) . Meta-analysis was performed for MI, TLR, major adverse cardiac events (MACE), and ST; showing statistically nonsignificant difference for the aforementioned outcomes with a slight trend favouring BRS except in stent thrombosis.

Conclusion

There was no statistical difference between BRS and DBS in the treatment of CBL in terms of MI, ST, TLR or MACE. There was, however, a trend for a more favourable outcome on all measures for BRS other than stent thrombosis. this study showed a lack of randomised controlled trials in this subject which may be an area for researchers to investigate further in the future.
Protective role of protein Klotho biomarker in acute heart failure
Authors: Plonka J , Olejnik A , Klus A , Gawrylak- Dryja E , Wezyk-Wylegala N , Rzepiela L , Dabrowska K , Bil-Lula I , Gierlotka M
Published: May 2022

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by a grant from the Institute of Medical Sciences, Univeristy of Opole, Poland

Background

Klotho is an antiaging protein with pleiotropic actions that exerts organ protection. There is evidence that Klotho protein acts as a human aging-suppression molecule and correlates with life span, coronary artery disease, atherosclerosis, and osteoporosis. In laboratory models of damage, an increased expression of Klotho protein in human cardiac myocytes and release of Klotho protein into the extracellular space suggests a potential compensatory and cardioprotective effect. The aim of the present study was to assess changes of Klotho protein levels during an episode of acute heart failure (AHF) as well as its long-term prognostic utility in population of AHF patients compared to other biomarkers.

Methods

We analysed 112 consecutive patients admitted to ICCU between June 2019 and January 2021 due to hight-risk AHF. Blood samples were collected on admission, at discharge as well as at the 30-day. Patients were then followed-up for all-cause mortality and rehospitalizations due to heart failure.

Results

Patients (N=112; median age 68 years, 75% men, median left ventricular ejection fraction 30% [IQR 20-38%]) had median admission levels of Klotho protein = 670 pg/ml [501-851], FGF-23 = 1278 pg/ml [283-4429], NT-proBNP = 5361 ng/l [3019-13182], and GDF-15 = 4582 pg/ml [3028-9081]. Klotho protein decreased by 19% from admission to discharge and then increased by 13% from discharge to 30-day (P<0.001). During median 478 days follow-up 40 patients (36%) died or were hospitalised due to heart failure - they were older, more often with new onset AHF, of ischaemic aetiology and diabetics. Patients with lower levels of Klotho protein (in the 1st as well as in the 2nd quartile) had higher mortality (Figure). ROC analyses showed Klotho had comparable predictive value of unfavourable prognosis as other biomarkers (GDF-15, NT-proBNP).

Conclusion

The levels of Klotho protein in patients with AHF are higher compared to healthy population and they show dynamics dependent on the clinical state what indicates the utility of Klotho as a typical biomarker. Lower values of Klotho protein in AHF patients are associated with higher mortality which may suggests protective effect of higher Klotho levels.
Dual marker rule-out of non-AMI acute cardiovascular conditions in chest pain patients
Authors: Pedersen CK , Stengaard C , Boetker MT , Dodt KK , Soendergaard HM , Terkelsen CJ
Published: May 2022

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Danish Heart foundation

Independent Research Fund Denmark

Background

A dual marker strategy combining prehospital copeptin and in-hospital hs-cTnT has shown promising results in early rule out of AMI. This combination may also allow for rule out of other life-threatening conditions in patients presenting with chest pain. Copeptin is a nonspecific marker of endogenous stress and elevated levels would be expected in life-threatening conditions causing haemodynamic instability. Elevated troponin levels due to secondary acute myocardial injury is often seen in life-threatening conditions (e.g. pulmonary embolism and aortic dissection).

Purpose

To evaluate if an accelerated DMS combining prehospital copeptin and 1st in-hospital hs-cTnT can rule out other life threatening conditions than AMI in patients with symptoms suggestive of AMI.

Methods

The diagnostic performance of the accelerated DMS regarding serious cardiovascular conditions other than AMI was compared in patients with suspected AMI from a randomized, controlled, multicentre trial. Serious cardiovascular conditions included pulmonary embolism, pneumothorax, ventricular tachycardia, and aortic dissection. Diagnoses were retrieved from the Danish National Registry of Patients. Serious conditions were ruled out if copeptin was below 9.8 pmol/L (95th percentile) and troponin T was below 14 ng/L (99th percentile).

Results

In 3,426 with both prehospital copeptin and 1st in-hospital troponin T available, 39 patients received a diagnosis of one of the predefined serious cardiovascular condition during index admission. The accelerated DMS performed with a sensitivity of 82%, a specificity of 48% and a NPV of 99.5%.

Conclusion(s)

Accelerated DMS did not perform with acceptable sensitivity for the rule out of other life-threatening conditions in patients with suspected AMI.
Clinical value of troponin profiles in early post coronary artery bypass grafting acute care in advanced chronic kidney disease patients: An insight into perioperative patient characteristics
Authors: Gobolos L , Manla Y , Khan N , Bhatnagar G , Aljabery Y , Sanger S , Alsindi F , Hamour I , Attallah N , Hogan M
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Background and Aims

Diagnosis of type V myocardial infarction (MI) in patients with advanced chronic kidney disease (CKD) undergoing coronary revascularisation surgery (CAB) presents a clinical challenge. We describe postoperative serum troponin (cTn) trends after CAB in CKD stages IV-V, and assess associations with gender, preoperative dialysis, clinical presentation and CAB method.

Methods

We analysed 51 patients with CKD stage IV-V who underwent CAB at a single centre between 2016-2021. Data on patient characteristics, CAB surgery, and cTn (T) levels were collected retrospectively, and independently for our Society of Thoracic Surgeons database. Patient characteristics were compared between patients undergoing on-pump vs off-pump CAB using appropriate testing methods. The differences in cTn trends between males vs females, acute coronary syndrome (ACS) vs stable angina, patients undergoing preoperative dialysis vs not, and on-pump vs off-pump CAB at different time points were assessed using repeated measurements, and a p value<0.05 was considered to be statistically significant.

Results

Among 51 patients with stage IV (47%) and V (53%) CKD, off-pump CAB was conducted in 41% (21) of the patients, while the rest underwent on-pump CAB. Patients in the off-pump group were older (62.2 vs 56.6 years, p=0.03), and there were no other statistically significant differences in patient characteristics between groups (Table). Over time, cTn levels increased from 0.34 [0.08-0.9] ng/mL at 24h preoperatively to achieve a peak of 0.75 [0.44-1.7] ng/mL at 18h postoperatively. When comparing cTn trends according to gender, preoperative dialysis, clinical presentation and CAB method, cTn levels were higher in males, patients presenting with ACS, patients who did not undergo preoperative dialysis, and in the on-pump CAB group (Figure). However, in this small sample size study, between-group differences in cTn trends did not achieve statistical significance (p=0.26, p=0.18, p=0.5, and p=0.28, respectively).

Conclusion

Serum troponin levels peaked consistently by 18h postoperatively in advanced CKD patients undergoing CAB. In addition, males, ACS, on-pump CAB, and non-preoperatively dialysed patients had higher levels of cTn. Further large scale studies are required to definitively evaluate the diagnostic utility and cTn cut-off in this high-risk population.
Vascular biomechanics and molecular disease activity in the thoracic aorta: a novel imaging method
Authors: Minderhoud Savine C S , Fletcher Alexander J , MacNaught Gillian , Cadet Sebastien , Korteland Suze-Anne , Kardys Isabella , Rizopoulos Dimitris , Slomka Piotr , Newby David E , Roos-Hesselink Jolien W , Walker Niki L , Semple Scott , Hirsch Alexander , Dweck Marc R , Wentzel Jolanda J
Published: May 2022

Aims

The influence haemodynamics have on vessel wall pathobiology in aortic disease is incomplete. This aim of this study was to develop a repeatable method for assessing the relationship between aortic wall shear stress (WSS) and disease activity by fusing 4D flow cardiovascular magnetic resonance (CMR) with hybrid positron emission tomography (PET).

Methods and results

As part of an ongoing clinical trial, patients with bicuspid aortic valve (BAV) were prospectively imaged with both 18F-sodium fluoride (18F-NaF) PET, a marker of calcification activity, and 4D flow CMR. We developed novel software allowing accurate 3D co-registration and high-resolution comparison of aortic peak systolic WSS and 18F-NaF PET uptake (maximum tissue-to-background ratio). Intra-observer repeatability of both measurements was determined using Bland–Altman plots and intra-class correlation coefficients (ICCs). The relationship between localized WSS and 18F-NaF uptake was analysed using linear mixed-effect models. Twenty-three patients with BAV (median age 50 [44–55] years, 22% female) were included. Intra-observer repeatability for WSS (ICC = 0.92) and 18F-NaF (ICC = 0.91) measurements obtained within 1.4 ± 0.6 cm2 regions of interest was excellent. On multivariable analysis, 18F-NaF PET uptake was independently and negatively associated with WSS as well as diastolic blood pressure (both P < 0.05), adjusted for age.

Conclusion

Fused assessment of WSS and 18F-NaF PET uptake is feasible and repeatable, demonstrating a clear association between these two factors. This high spatial resolution approach has major potential to advance our understanding of the relationship between vascular haemodynamics and disease activity.
A clinician’s guide to understanding and critically appraising machine learning studies: a checklist for Ruling Out Bias Using Standard Tools in Machine Learning (ROBUST-ML)
Authors: Al-Zaiti Salah S , Alghwiri Alaa A , Hu Xiao , Clermont Gilles , Peace Aaron , Macfarlane Peter , Bond Raymond
Published: May 2022

Developing functional machine learning (ML)-based models to address unmet clinical needs requires unique considerations for optimal clinical utility. Recent debates about the rigours, transparency, explainability, and reproducibility of ML models, terms which are defined in this article, have raised concerns about their clinical utility and suitability for integration in current evidence-based practice paradigms. This featured article focuses on increasing the literacy of ML among clinicians by providing them with the knowledge and tools needed to understand and critically appraise clinical studies focused on ML. A checklist is provided for evaluating the rigour and reproducibility of the four ML building blocks: data curation, feature engineering, model development, and clinical deployment. Checklists like this are important for quality assurance and to ensure that ML studies are rigourously and confidently reviewed by clinicians and are guided by domain knowledge of the setting in which the findings will be applied. Bridging the gap between clinicians, healthcare scientists, and ML engineers can address many shortcomings and pitfalls of ML-based solutions and their potential deployment at the bedside.
Machine learning cardiac-MRI features predict mortality in newly diagnosed pulmonary arterial hypertension
Authors: Alabed Samer , Uthoff Johanna , Zhou Shuo , Garg Pankaj , Dwivedi Krit , Alandejani Faisal , Gosling Rebecca , Schobs Lawrence , Brook Martin , Shahin Yousef , Capener Dave , Johns Christopher S , Wild Jim M , Rothman Alexander M K , van der Geest Rob J , Condliffe Robin , Kiely David G , Lu Haiping , Swift Andrew J
Published: May 2022

Aims

Pulmonary arterial hypertension (PAH) is a rare but serious disease associated with high mortality if left untreated. This study aims to assess the prognostic cardiac magnetic resonance (CMR) features in PAH using machine learning.

Methods and results

Seven hundred and twenty-three consecutive treatment-naive PAH patients were identified from the ASPIRE registry; 516 were included in the training, and 207 in the validation cohort. A multilinear principal component analysis (MPCA)-based machine learning approach was used to extract mortality and survival features throughout the cardiac cycle. The features were overlaid on the original imaging using thresholding and clustering of high- and low-risk of mortality prediction values. The 1-year mortality rate in the validation cohort was 10%. Univariable Cox regression analysis of the combined short-axis and four-chamber MPCA-based predictions was statistically significant (hazard ratios: 2.1, 95% CI: 1.3, 3.4, c-index = 0.70, P = 0.002). The MPCA features improved the 1-year mortality prediction of REVEAL from c-index = 0.71 to 0.76 (P ≤ 0.001). Abnormalities in the end-systolic interventricular septum and end-diastolic left ventricle indicated the highest risk of mortality.

Conclusion

The MPCA-based machine learning is an explainable time-resolved approach that allows visualization of prognostic cardiac features throughout the cardiac cycle at the population level, making this approach transparent and clinically interpretable. In addition, the added prognostic value over the REVEAL risk score and CMR volumetric measurements allows for a more accurate prediction of 1-year mortality risk in PAH.
Late outcome of extracardiac Fontan patients: 32 years of follow-up
Authors: Giannico Salvatore , Trezzi Matteo , Cantarutti Nicoletta , Cafiero Giulia , Ravà Lucilla , Adorisio Rachele , Brancaccio Gianluca , Albanese Sonia , Drago Fabrizio , Carotti Adriano , Amodeo Antonio , Galletti Lorenzo
Published: May 2022

OBJECTIVES

We sought to evaluate the long-term survival and risk factors for morbidity and mortality in our cohort of patients after extracardiac (EC) Fontan.

METHODS

We collected and analysed follow-up data until September 2020 for all patients who underwent EC Fontan operation at our institution from November 1988 to November 2015.

RESULTS

Out of 406 patients treated with EC Fontan at a mean age of 5.4 ± 4.5 years, 372 (91.6%) were discharged home; 15% were lost to follow-up. The median follow-up was 14.6 years (interquartile range 8.7–20.3). Two hundred patients (54%) had a good long-term outcome, with an event-free long-term survival, but late adverse events of any kind needing interventional or surgical reoperations were reported in 128 patients (34%). Forty-four patients (12%) developed late Fontan failure. Thirty-seven survivors (10%) had late arrhythmias, with the need for pacemaker implantation. Obstruction of the cavopulmonary pathway occurred in 49 patients (13%), but just 8 patients needed conduit surgical replacement. At 32 years, the survival probability was 84%. The risk of orthotopic heart transplant, considering death as a competing event (showed as cumulative incidence), was 12.5%. A preoperative diagnosis of hypoplastic left heart syndrome was an independent risk factor for the need for heart transplant.

CONCLUSIONS

The EC Fontan shows satisfactory long-term survival and low incidence of adverse events and late failure. Conduit replacement is rare, and its longevity may not represent a substantial issue in these patients. However, as with other technical variants, the need for reoperations during long-term follow-up is a significant challenge.
Anatomical reconstruction of proximal coronary artery stenosis in children
Authors: Krokovay A , Prêtre R , Kretschmar O , Knirsch W , Valsangiacomo Buechel E , Dave H
Published: May 2022

OBJECTIVES

Timing and method of surgical reconstruction for non-sclerotic proximal coronary artery stenosis, occurring de novo or post-coronary artery transfer, are evolving. We have pursued a technique of anatomical reconstruction of ostial and short segment proximal coronary artery stenosis and atresia in children, using patch plasty or interposition vein graft. Here, we discuss the medium- to long-term outcomes.

METHODS

Nine consecutive children undergoing 10 left main coronary artery reconstructions using autologous great saphenous vein patch (n = 4), autologous pericardium (n = 4), xenopericardium (n = 1) or great saphenous vein interposition graft (n = 1) were retrospectively analysed. Complementary wedge resection of the stenotic coronary ostium was performed in chronic cases.

RESULTS

The aetiology of coronary artery stenosis was post-arterial switch operation (n = 6), Takayasu’s arteritis (n = 1), idiopathic left main coronary artery atresia (n = 1) and anomalous origin of the left coronary artery from the pulmonary artery (n = 1). The median age and weight at operation were 0.15 (range 0.01–13.1) years and 4.4 (range 3–13.1) kg, respectively. Survival was 100% at the medi follow-up of 12.6 (range 1–19.2) years. All patients showed normal left ventricular ejection fraction on transthoracic echocardiogram. In 1 patient, kinking of the proximal left circumflex artery resulted in non-significant obstruction. In all other cases, follow-up catheter angiography revealed unobstructed coronary arteries. Cardiac magnetic resonance tomography showed no significant perfusion deficit in any child.

CONCLUSIONS

Anatomical reconstruction of the proximal left coronary artery using autologous saphenous vein may allow optimal restoration of physiological coronary blood flow, keeping the option of future coronary bypass operation open.
Preferential associations of soil fungal taxa under mixed compositions of eastern American tree species
Authors: Kutos Steve , Barnes Elle M , Bhutada Arnav , Lewis J D
Published: May 2022

Soil fungi are vital to forest ecosystem function, in part through their role mediating tree responses to environmental factors, as well as directly through effects on resource cycling. While the distribution of soil fungi can vary with abiotic factors, plant species identity is also known to affect community composition. However, the particular influence that a plant will have on its soil microbiota remains difficult to predict. Here, we paired amplicon sequencing and enzymatic assays to assess soil fungal composition and function under three tree species, Quercus rubra, Betula nigra, and Acer rubrum, planted individually and in all combinations in a greenhouse. We observed that fungal communities differed between each of the individual planted trees, suggesting at least some fungal taxa may associate preferentially with these tree species. Additionally, fungal community composition under mixed-tree plantings broadly differed from the individual planted trees, suggesting mixing of these distinct soil fungal communities. The data also suggest that there were larger enzymatic activities in the individual plantings as compared to all mixed-tree plantings which may be due to variations in fungal community composition. This study provides further evidence of the importance of tree identity on soil microbiota and functional changes to forest soils.
Stability study of fortified low-fat spreads with preservatives
Authors: Kharb Suman , Thompkinson Dilip Kumar , Kumari Harshita
Published: May 2022

Physicochemical variations in products are known to occur depending on storage conditions. This study examined the effects of storage time on the physicochemical, sensory, rheological, and microbiological properties of fortified low-fat spreads. Fortified spreads containing potassium sorbate (PS; 0.05% and 0.1%) or MicroGard 100 (MG; 0.5% and 1%) as preservatives and a control spread (CS) were packed in presterilized airtight polyethylene jars and their shelf lives were investigated by storage at (5±1) °C for 91 d. Based on the physicochemical properties, the addition of preservatives inhibited the formation of free fatty acids and thiobarbituric acid and influenced the pH and acidity. The emulsion stability of the preserved samples was greater than that of the CS after 14 d. As storage progressed, the sensory and rheological properties of the CS deteriorated continuously, whereas significantly smaller changes were observed for the samples containing 0.1% PS and 1% MG. The surface growth of yeasts and molds was the main cause of spoilage, particularly in the CS. For all the samples, the standard plate counts and the yeast and mold counts increased during storage. In contrast, the coliform counts were zero, indicating that the samples were manufactured and stored under hygienic conditions. The samples containing lower levels of preservatives (0.05% PS and 0.5% MG) were acceptable for 70 d and 77 d as compared to 49 d for the CS. Notably, the addition of 0.1% PS and 1% MG extended the shelf life to 91 d.
Contamination of microgreens by Salmonella enterica and Escherichia coli is influenced by selection breeding in chicory (Cichorium intybus L.)
Authors: Lenzi Anna , Baldi Ada , Lombardelli Letizia , Truschi Stefania , Marvasi Massimiliano , Bruschi Piero
Published: May 2022

The aim of this study was to assess whether selection breeding in chicory (Cichorium intybus L.) led changes in the susceptibility to Salmonella enterica and Escherichia coli contamination and whether the anatomical traits of the leaves are involved in the possible changes. Five chicory genotypes subjected to different intensities of selection were compared at the microgreen stage. Bacterial retention was evaluated after leaf incubation for 1.5 h on the surface of the bacterial suspension, followed by rinsing, grinding, plating on selective media, and colony forming unit (CFU) counting. The density of stomata and trichomes, total stomatal length and width, stomatal pit width, surface roughness and sharpness were evaluated. The intensively selected genotype (Witloof) was significantly more prone to contamination (2.9±0.3 lg CFU/cm2) as the average of the two bacterial types than the wild accession (Wild; 2.3±0.4 lg CFU/cm2) and the moderately selected genotypes (two leaf chicories, Catalogna type, and root chicory ‘Magdeburg’; on average, 1.9±0.3 lg CFU/cm2). Witloof microgreens also showed larger stomata (on average +34% for stoma width and +44% for pit width), which could justify, at least in part, the higher susceptibility to enterobacterial contamination. In fact, when contamination was performed in the dark (closed stomata), the bacterial retention in Witloof was significantly reduced in comparison with the opened stomata (–44%) and in Wild (–26%). Differences in retention between Witloof and Wild were still observed after UV treatment. The hierarchical clustering performed by grouping the leaf anatomical features was consistent with the chicory genetic groups. Our results suggest that the domestication process can affect the safety of produce and that the micromorphological traits of the leaves may be involved.
Dietary vitamin B12 regulates chemosensory receptor gene expression via the MEF2 transcription factor in Caenorhabditis elegans
Authors: McDonagh Aja , Crew Jeannette , van der Linden Alexander M
Published: May 2022

Dynamic changes in chemoreceptor gene expression levels in sensory neurons are one strategy that an animal can use to modify their responses to dietary changes. However, the mechanisms underlying diet-dependent modulation of chemosensory gene expression are unclear. Here, we show that the expression of the srh-234 chemoreceptor gene localized in a single ADL sensory neuron type of Caenorhabditis elegans is downregulated when animals are fed a Comamonas aquatica bacterial diet, but not on an Escherichia coli diet. Remarkably, this diet-modulated effect on srh-234 expression is dependent on the micronutrient vitamin B12 endogenously produced by Comamonas aq. bacteria. Excess propionate and genetic perturbations in the canonical and shunt propionate breakdown pathways are able to override the repressive effects of vitamin B12 on srh-234 expression. The vitamin B12-mediated regulation of srh-234 expression levels in ADL requires the MEF-2 MADS domain transcription factor, providing a potential mechanism by which dietary vitamin B12 may transcriptionally tune individual chemoreceptor genes in a single sensory neuron type, which in turn may change animal responses to biologically relevant chemicals in their diet.
A scoping review of distributed ledger technology in genomics: thematic analysis and directions for future research
Authors: Beyene Mikael , Toussaint Philipp A , Thiebes Scott , Schlesner Matthias , Brors Benedikt , Sunyaev Ali
Published: May 2022

Objective

Rising interests in distributed ledger technology (DLT) and genomics have sparked various interdisciplinary research streams with a proliferating number of scattered publications investigating the application of DLT in genomics. This review aims to uncover the current state of research on DLT in genomics, in terms of focal research themes and directions for future research.

Materials and Methods

We conducted a scoping review and thematic analysis. To identify the 60 relevant papers, we queried Scopus, Web of Science, PubMed, ACM Digital Library, IEEE Xplore, arXiv, and BiorXiv.

Results

Our analysis resulted in 7 focal themes on DLT in genomics discussed in literature, namely: (1) Data economy and sharing; (2) Data management; (3) Data protection; (4) Data storage; (5) Decentralized data analysis; (6) Proof of useful work; and (7) Ethical, legal, and social implications.

Discussion

Based on the identified themes, we present 7 future research directions: (1) Investigate opportunities for the application of DLT concepts other than Blockchain; (2) Explore people’s attitudes and behaviors regarding the commodification of genetic data through DLT-based genetic data markets; (3) Examine opportunities for joint consent management via DLT; (4) Investigate and evaluate data storage models appropriate for DLT; (5) Research the regulation-compliant use of DLT in healthcare information systems; (6) Investigate alternative consensus mechanisms based on Proof of Useful Work; and (7) Explore DLT-enabled approaches for the protection of genetic data ensuring user privacy.

Conclusion

While research on DLT in genomics is currently growing, there are many unresolved problems. This literature review outlines extant research and provides future directions for researchers and practitioners.
Influence of environmental factors and genetic variation on mitochondrial DNA copy number
Authors: Sanglard Leticia P , Kuehn Larry A , Snelling Warren M , Spangler Matthew L
Published: May 2022

Mitochondrial DNA copy number (mtDNA CN) has been shown to be highly heritable and associated with traits of interest in humans. However, studies are lacking in the literature for livestock species such as beef cattle. In this study, 2,371 individuals from a crossbred beef population comprising the Germplasm Evaluation program from the U.S. Meat Animal Research Center had samples of blood, leucocyte, or semen collected for low-pass sequencing (LPS) that resulted in both nuclear DNA (nuDNA) and mitochondrial DNA (mtDNA) sequence reads. Mitochondrial DNA CN was estimated based on the ratio of mtDNA to nuDNA coverages. Genetic parameters for mtDNA CN were estimated from an animal model based on a genomic relationship matrix (~87K SNP from the nuDNA). Different models were used to test the effects of tissue, sex, age at sample collection, heterosis, and breed composition. Maternal effects, assessed by fitting a maternal additive component and by fitting eleven SNP on the mtDNA, were also obtained. As previously reported, mtDNA haplotypes were used to classify individuals into Taurine haplogroups (T1, T2, T3/T4, and T5). Estimates of heritability when fitting fixed effects in addition to the intercept were moderate, ranging from 0.11 to 0.31 depending on the model. From a model ignoring contemporary group, semen samples had the lowest mtDNA CN, as expected, followed by blood and leucocyte samples (P ≤ 0.001). The effect of sex and the linear and quadratic effects of age were significant (P ≤ 0.02) depending on the model. When significant, females had greater mtDNA CN than males. The effects of heterosis and maternal heterosis were not significant (P ≥ 0.47). The estimates of maternal and mtDNA heritability were near zero (≤0.03). Most of the samples (98%) were classified as haplogroup T3. Variation was observed in the mtDNA within Taurine haplogroups, which enabled the identification of 24 haplotypes. These results suggest that mtDNA CN is under nuclear genetic control and would respond favorably to selection.