bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of intima media thickness in the assessment of the development of preclinical atherosclerosis
Authors: Najafov R N N
Published: October 2021

Background/Introduction

In the carotid arteries, an IMT >0.9 mm measured by Duplex sonography is considered abnormal and can be considered an independent predictor of preclinical atherosclerosis. IMT >1.5 mm can already be called an atherosclerotic plaque.

Purpose

The aim of this study was to investigate the age characteristics of the intima media thickness in the carotid arteries

Methods

The analysis was performed on the basis of retrospective observations of 483 patients who underwent ultrasound dopplerography during 2010–2017. The mean age of the studied patients was 53.28±14.06 (min 9, max 86 years), the standard mean error was ± 0.64. Among those examined, 165 (34.16%) were men and 318 (65.84%) were women. Measurements for IMT were performed on both the right and left: common, external, and internal carotid arteries. IMT is defined in the following ranges: <0.9 mm – normal thickness; 0.9–1.0 mm – intermediate thickness; >1.0 mm – increased thickness; ≥1.5 mm – atherosclerotic plaque.

Results

The comparison was made in 3 age groups: <40; 40–65; >65 years. 3 IMT values were taken: <0.9; 0.9–1.0; >1.0 mm. Indicators are calculated in both absolute numbers and percentages. The accuracy of the obtained results was checked by chi square statistics (p<0.05). There were 477 patients in the age group we studied. We lost 6 pts in this study. It was 90 pts at the age <40 years, 293 pts at the age 40–65 years, 94 pts at the age >65 years. It was 249 pts with IMT <0.9 mm, 107 pts with IMT 0.9 - 1.0 mm, 121 pts with IMT >1.0 mm. According to our results, it was IMT <0.9 mm in 87.78% (79 pts) cases at the age <40 years, 52.22% (153 pts) at the age 40–65 years, 18.09% (17 pts) at the age >65 years. IMT was found between 0.9 and 1.0 mm in 5.56% (5 pts) cases at the age <40 years, 47.71% (73 pts) at the age 40–65 years, 30.85% (29 pts) at the age >65 years. It was IMT >1.0 mm in 6.67% (6 pts) cases at the age <40 years, 22.87% (67 pts) at the age 40–65 years, 51.06% (48 pts) at the age >65 years.

Conclusion(s)

The prevalence of the IMT >1.0 mm more at the age >65 years (51.06%), IMT 0.9–1.0 mm more at the age 40–65 years (47.71%), IMT <0.9 mm more at the age <40 years (87.78%).

Funding Acknowledgement

Type of funding sources: None.
Restrictive vs liberal blood transfusion strategy in patients with symptomatic coronary artery disease: meta-analysis from randomized controlled trials
Authors: Maraey A , Elzanaty A , Elsharnoby H , Younes M , Salem M , Khalil M
Published: October 2021

Background

Anemia is common in patients with symptomatic coronary artery disease. Observational studies investigated blood transfusion threshold in symptomatic coronary artery disease but results were conflicting. Meta-analyses evaluating transfusion threshold utilized data mainly from observational trials but no meta-analysis, to our knowledge, used data solely from randomized clinical trials.

Objective

The goal of our study is to evaluate efficacy and safety outcomes in anemic patients presenting with symptomatic coronary artery disease using pooled data from randomized clinical trials.

Methods

We queried Medline, Embase and Cochrane data bases for randomized clinical trials comparing restrictive blood transfusion (defined as transfusion when hemoglobin is less than 8 gm/dl) vs liberal blood transfusion (transfusion when hemoglobin is less than 10 gm/dl) in patients presenting with symptomatic artery disease or acute coronary syndrome. We identified 3 randomized controlled trials; MINT, CRIT and REALITY trials. Data were pooled from 3 trials. Efficacy outcomes evaluated were all-cause mortality and New or recurrent myocardial infarction. Safety outcomes were congestive heart failure at 30-day follow up.

Results

A total of 820 patients were included in our meta-analysis; 420 patients in restrictive blood transfusion protocol and 400 in liberal blood transfusion protocol

There was no difference between two groups at 30-day follow up in all identified outcomes (all-cause mortality, new or recurrent myocardial infarction, and Congestive heart failure).

55 patients died (22/420 in restrictive group and 33/400 in liberal group). Risk ratio of all-cause mortality in restrictive group was 0.63 [95% CI (0.38–1.07), P=0.09, I2=30%].

15/420 in restrictive group and 16/400 in liberal group had new or recurrent myocardial infarction. Risk ratio of myocardial infarction in restrictive group was 0.91 [95% CI (0.46–1.80), P=0.78, I2=0%].

20/420 patients in restrictive group and 24/400 in liberal group had congestive heart failure with risk ratio of 0.80 [95% CI (0.19–3.37), P=0.30, I2=76%] in restrictive group.

Conclusion

Our meta-analysis showed similar outcomes between restrictive and liberal transfusion policies in patients presenting with symptomatic coronary artery disease of acute myocardial infarction. Our findings are consistent with available data about restricting transfusion in general population. Restricting blood transfusion might be cost-effective. Further studies are warranted to evaluate long term safety and efficacy of such approach.

Funding Acknowledgement

Type of funding sources: None.
Safety and efficacy of bivalirudin in diabetic acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI)
Authors: Golam Mostofa A , Parvin T , Masum Mandal R , Ali Ahsan S , Afrin R
Published: October 2021

Background

Prevention of hemorrhagic complications has emerged as a priority in patients undergoing Percutaneous Coronary Intervention (PCI) in addition to suppressing thrombotic complications. This goal is challenging to achieve in diabetic Acute Coronary Syndrome (ACS) patients as Diabetes Mellitus (DM) itself is a prothrombotic state with more pronounced vascular injury response and have a worse outcome after PCI compared with non-diabetic patients. In patients with ACS, Bivalirudin has been shown to result in similar rates of composite ischemia as Heparin plus GPI (GP IIb /IIIa inhibitor), while significantly reducing major bleeding and has received class I recommendation for PCI by American College of Cardiology (ACC 2013). Whether Bivalirudin is safe and effective specially in diabetic ACS patients undergoing PCI, as compared with Heparin (UFH) monotherapy, is unknown.

Purpose

To determine and compare the incidence of in-hospital and 30-day hemorrhagic complications and major adverse cardiac events (MACEs) as evidence of safety and efficacy using Bivalirudin versus Heparin in diabetic ACS patients undergoing PCI.

Methods

218 diabetic ACS patients (age>18 years and ≤75 years) who underwent PCI from May 2018 to April 2019 at University Cardiac Centre, BSM Medical University, Dhaka, Bangladesh were randomly assigned to have UFH or Bivalirudin. Before the guide wire crossed the lesion, 111 patients in the UFH group received a bolus of 70–100 U/kg (targeted activated clotting time, ACT: 200–250 s). 107 patients in the Bivalirudin group received a loading dose of 0.75 mg/kg, followed by an infusion of 1.75 mg/kg/h for up to 4 hours. Dual antiplatelet (DAPT) loading as Aspirin 300 mg plus P2Y12 inhibitors (Clopidogrel 600 mg or Prasugrel 60 mg or Ticagrelor 180 mg) was given in all patients before the procedure. The maintenance dose of DAPT was continued for at least one month and patients were followed telephonically up to 30 days. The outcome measures were in-hospital and 30-day hemorrhagic complications and MACEs [death, MI, target vessel revascularization (TVR) and stroke].

Results

Patients treated with Bivalirudin compared with Heparin had a significantly lower in-hospital incidence of QMI (0% vs. 6%; p=0.03) and major bleeding (0% vs. 7%; p=0.02). However, the incidence of cardiac death, stent thrombosis, TVR were no differences between two groups (p>0.05). There was only one NQMI in the Bivalirudin group as opposed to 8% in the Heparin group in 30 days following stenting (p=0.04).

Conclusion

In diabetic ACS patients undergoing PCI, Bivalirudin is safe and effective as it reduces immediate and short-term hemorrhagic complications as well as MACEs as compared with Heparin.

Funding Acknowledgement

Type of funding sources: None.
STEMI patients in the first and second wave of COVID-19 pandemic in Slovenia
Authors: Sinkovic A , Krasevec M , Golub J , Suran D , Marinsek M , Markota A
Published: October 2021

Introduction

Countries, severly hit by COVID-19 pandemic in spring 2020, reported reduced admissions and increased mortality of STEMI patients. The first wave of COVID-19 pandemic in Slovenia was mild, but in the second wave (October to December 2020) COVID-19 cases and fatalities significantly increased. To overcome the pandemic, restrictions to full lockdown, rapid redeployment and mobilization of healthcare resources, as well as reduction or delayed hospital admissions for acute non-communicable conditions were were undertaken.

Purpose

To evaluate STEMI admissions, the delay in treatment, complications and mortality of STEMI patients in the first and second wave of COVID-19 pandemic and comparison of data to 3 months (March-May) in 2019.

Methods

We retrospectively analysed the data of STEMI patients, admitted in March to May 2019 and in the first (March-May) and in the second wave (October-December) of the COVID-19 pandemic in 2020. We compared STEMI admissions, age, gender, comorbidities, time to primary coronary intervention (PPCI), the rate of PPCI, TIMI III flow after PPCI, prior resuscitations, hospital complications such as heart failure, arrhythmias, bleedings, acute kidney injury and mortality between 2019 and both waves of COVID-19 pandemic.

Results

Between STEMI patients in 2019 and patients in the first and the second wave of COVID-19 pandemic there were nonsignificant differences in STEMI admissions (90 patients vs 96 patients vs 81 patients), in gender, age, comorbidities, the rate of primary percutaneous intervention (PPCI, 94.4% vs 94.8% vs 91.4%), TIMI III flow after PPCI, anterior STEMI, in prior resuscitations (10% vs 10.4% vs 16%). Compared to 2019, admission acute heart failure was nonsignificantly increased in COVID-19 pandemic (30% vs 34.4% vs 39.5%). Within the first 3 hours of STEMI PPCI was performed nonsignificantly less likely in the first wave and significantly less likely in the second wave (35.5%* vs 30.2% vs 19.8%*, *p=0.037) in comparison to 2019. The incidence of acute kidney injury was similar in the first wave, but nonsignificantly increased in the second wave (6.6% vs 5.2% vs 9.8%), compared to 2019 and hospital infection was nonsignificantly increased in both COVID-19 periods (15.6% vs 20.8% vs 27.2%). In hospital heart failure was nonsignificantly increased in the first wave and significantly increased in the second one (23.3%* vs 27.1% vs 42%*, *p=0.015), as well as mitral regurgitation (10%* vs 18.8% vs 26.9%*, *p=0.008). Hospital mortality was nonsignificantly increased in bothe waves of the pandemic (8.9% vs 9.4% vs 13.6%).

Conclusions

In paralell to the increased severity of COVID-19 pandemic in the second wave there was less STEMI admissions, significantly less timely performed PPCI with significantly increased hospital heart failure, resulting in nonsignificantly increased hospital mortality.

Funding Acknowledgement

Type of funding sources: None.
Association between off-hours admission with acute myocardial infarction and in-hospital mortality
Authors: Song J , Bai X , Li X , Li J , Zheng X
Published: October 2021

Background

The effect of time of admission on clinical outcomes in patients with acute myocardial infarction (AMI) is still a matter of debate.

Purpose

To investigate the association between off-hours admission and in-hospital mortality in patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI).

Methods

We used a two-stage, random sampling method to create a nationally representative sample of patients with AMI in 167 Chinese hospitals in four years (2001, 2006, 2011, and 2015). Off-hours were defined as 20:00–07:59 and on-hours as 08:00–19:59. We used hierarchical logistic regression model to examine whether off-hour admissions were associated with in-hospital mortality and 7-day mortality. Inverse-probability weighting propensity score analysis was also conducted to assess the robustness of the results.

Results

We identified 25654 patients admitted with AMI (median age 67.0 years; 31.6% women), of whom 20133 (78.5%) were diagnosed as STEMI and 5521 (21.5%) as NSTEMI. There were 5368 (26.7%) admissions for STEMI, and 1356 (24.6%) for NSTEMI occurring during off-hours, respectively. After adjusting for case mix, year of admission, comorbidities, clinical presentation, and in-hospital treatments, a significant association was observed between off-hours admissions and in-hospital mortality among the patients with STEMI (adjusted OR 1.14; 95% CI 1.01 to 1.28). The magnitude of the association became greater in the secondary analysis with 7-day mortality as the outcome (adjusted OR 1.16; 95% CI 1.02 to 1.31). But among patients with NSTEMI, no significant association was observed for in-hospital and 7-day mortality. Propensity score analysis showed similar results to hierarchical logistic model for both outcomes in patients with STEMI and NSTEMI.

Conclusion

Off-hours admission with STEMI is associated with higher in-hospital mortality. Reducing the disparity of care of STEMI by the time of admission represents a potential opportunity for quality improvement in China.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): National Key Research and Development Program (2017YFC1310803, 2017YFC1310801) from the Ministry of Science and Technology of China
Cardiac rupture – the most serious complication of Takotsubo syndrome
Authors: Zalewska-Adamiec M , Bachorzewska-Gajewska H , Dobrzycki S
Published: October 2021

Background

The most serious complication of the acute Takotsubo phase is a myocardial perforation, which is rare, but it usually results in the death of the patient.

Methods

In the years 2008–2020, 265 patients were added to the Podlasie Takotsubo Registry. Cardiac rupture was observed in five patients (1.89%), referred to as the Takotsubo syndrome with complications of cardiac rupture (TS+CR) group. The control group consisted of 50 consecutive patients with uncomplicated TS. The diagnosis of TS was based on the Mayo Clinic Criteria.

Results

Cardiac rupture was observed in women with TS aged 74–88 years. Patients with TS and CR were older (82.20 vs. 64.84; p=0.011), than the control group, and had higher troponin, creatine kinase, aspartate aminotransferase, and blood glucose levels (168.40 vs. 120.67; p=0.010). The TS+CR group demonstrated a higher heart rate (95.75 vs. 68.38; p<0.0001) and the Global Registry of Acute Coronary Events (GRACE) scores (186.20 vs. 121.24; p<0.0001) than the control group. In patients with CR, ST segment elevation was recorded significantly more often in the III, V4, V5 and V6 leads. Left ventricular free wall rupture was noted in four patients, and in one case, rupture of the ventricular septum. In a multivariate logistic regression, the factors that increase the risk of CR in TS were high GRACE scores, and the presence of ST segment elevation in lead III.

Conclusions

Cardiac rupture in TS is rare but is the most severe mechanical complication and is associated with a very high risk of death. The main risk factors for left ventricular perforation are female gender, older age, a higher concentration of cardiac enzymes, higher GRACE scores, and ST elevations shown using electrocardiogram (ECG).

Funding Acknowledgement

Type of funding sources: None.
Corticosteroids in tuberculous pericarditis whit severe pericardial effusion to avoid constriction: a retrospective study in HIV-negative population
Authors: Blanco Ferri J , Pacheco G P
Published: October 2021

The role of corticosteroids in the treatment of tuberculous aetiology pericarditis without human immunodeficiency virus (HIV) is not well defined. Is unclear if associating corticoids to regular antibiotic therapy for tuberculosis, can prevent the progression of a severe pericardial effusion to constrictive pericarditis. Despite that, in countries where tuberculosis is an endemic disease and mostly it's not related to HIV, the use of corticosteroids is a common practice, as a part of a strategy to avoid progression of a severe pericardial effusion to a constrictive pericarditis. Our aim is to describe the clinical course of the patients with severe pericardial effusion of tuberculous aetiology and no echocardiographic sings of constriction, distinguishing those who used corticosteroids from those who didn't. We conducted a retrospective study, analyzing the clinical files of 40 patients treated in one hospital in a 5 years period (2016–2021). All of these patients were diagnosed whit severe pericardial effusion of tuberculous aetiology and no signs of constrictive pericarditis, they all finished their specific antibiotic treatment protocol according national guidelines and had at least 2 years of clinical follow from the time of the diagnosis. We found that the mean age was 54 years, 55% were men and 45% women. The mean follow up was 2.6 years. In all patients pericardial drainage was preformed, 60.5% using closed pericardiocentesis and 39.5% using open surgical techniques. 22 patients (55%) received prednisone that was initiated whit a dose of 1mg/kg daily that was reduced weekly in order to complete a 2 month cycle. The other 18 patients (45%) didn't received corticosteroids. In the prednisone group, 3 patients develop constrictive pericarditis during the time of follow up (13.6% of the prednisone group) while 7 patients of the non-corticosteroids group (38.8%) develop constrictive pericarditis. These retrospective study shows that there is a potential reduction in the progression to constrictive pericarditis whit the use of prednisone in HIV negative patients whit severe pericardial effusion of tuberculous aetiology, we need to perform prospective, controlled, blind and multicenter studies, designed to evidence the real effect of these strategy.

Funding Acknowledgement

Type of funding sources: None. Cases of contriction in both groups
Efficacy of coronary intravascular lithotripsy in coronary stenosis with severe calcification: a systematic review and meta-analysis
Authors: Ktenopoulos N K , Sagris M , Tzoumas A T
Published: October 2021

Introduction

Coronary calcification impedes proper stent deployment and expansion leading to an increased risk of adverse outcomes. Coronary Intravascular Lithotripsy (IVL) technology uses localized pulsative sonic pressure waves to disrupt subendothelial calcification and constitutes a promising technique for patients with severe coronary calcification.

Purpose

Our aim was to systematically review and summarize available data regarding the safety and efficacy of IVL in preparing severely calcified coronary plaques before stenting.

Methods

This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS and Cochrane databases, from their inception to February 20, 2021 for studies assessing characteristics and outcomes of patients undergoing IVL before stent implantation. A random effects model meta-analysis was performed to assess the diameter of the vessel lumen before and after IVL along with the presence of major adverse cardiac events (MACE).

Results

Eight studies comprising 971 patients were included in this meta-analysis. Mean age was 72.22±8.8 years and the majority of patients were males (78.4%). The overall success rate was 94% (95% CI: 90%-98%), while the in-hospital and 30-days incidence of MACE, MI and death were 8% (95% CI: 3%-14%), 10% (95% CI: 7%-14%), and 1% (95% CI: 0%-1%), respectively. There was a significant increase in the vessel diameter (SMD: 4.03, 95% CI: 3.32–4.74, I2=92%) and the lumen area (SMD: 1.17, 95% CI: 0.78–1.55, I2=84.7%), while decrease was observed in the diameter stenosis (SMD: −6.29, 95% CI: −7.65 to −4.92, I2=96.4%) post-IVL when compared to pre-IVL. Mean acute luminal gain following IVL was estimated to be 1.54±0.5mm.

Conclusions

IVL seems to be an effective and safe technique for preparing severely calcified lesions before PCI. Future prospective cohorts are needed to validate our results.

Funding Acknowledgement

Type of funding sources: None.
Value of CHA2DS2-VASc score and safe contrast volume for early detection of contrast induced nephropathy after percutaneous coronary intervention
Authors: Khalil W , Gouda M , Gamal M , Alshaer M
Published: October 2021

Background

The CHA2DS2-VASc score is utilized to order the danger of embolization in atrial fibrillation (AF). Also it has been assessed to expect the worse clinical scenario in acute coronary syndrome patients, regardless of having AF. Therefore, the study aim was to use CHA2DS2-VASc score that has such a large area of use and the safe contrast volume – that represented by volume of the dye to creatinine clearance ratio (V/CrCl) – for contrast induced nephropathy (CIN) early detection after PCI.

Patients and methods

A total of 259 patients who underwent elective or primary PCI were enrolled in the study. For each patient, The CHA2DS2-VASc score and V/CrCl was evaluated. The patients in our study were divided, according to CIN development to two groups. CIN was identified as a rise in serum creatinine >0.5 mg/dl or >25% increase in baseline within48 to 72 hours after PCI. Statistical analysis: the receiver operating characteristic analysis was used to detect the best cut off values to predict CIN, and we concluded the independent predictors of CIN through multivariate logistic regression analysis.

Results

There was significant positive correlation between Mehran score and CHA2DS2-VASc score. Independent predictors of CIN were Mehran score, V/CrCl ratio>3.2 and CHA2DS2-VASc >3, CHF or EF <40%, hypotension, anemia, primary PCI and weight. If the patient had (CHA2DS2-VASc score>3 or V/CrCl >3.2), as a single predictor, we can predict CIN with (sensitivity 96.97%, 95% CI 0.71 to 0.82).

Conclusion

The Mehran score, V/CrCl ratio and CHA2DS2-VASc score are strong predictors of CIN, and we can use CHA2DS2-VASc score and safe contrast volume for early detection of CIN after PCI.

Funding Acknowledgement

Type of funding sources: None.
Sex-related differences in long-term mortality after coronary artery bypass graft surgery: a systematic review and meta-analysis
Authors: Al-Sadawi M , Kane J , Stevens G A , Parikh P
Published: October 2021

Background

This meta-analysis assessed the sex-related differences in long-term mortality (>7 years) after Coronary Artery Bypass Graft (CABG) Surgery.

Purpose

Women has higher incidence of short-term cardiovascular mortality after CABG compared to men. However, data about long-term differences are controversial.

Methods

We searched the databases for studies reporting sex-specific mortality following CABG including Ovid MEDLINE, Ovid, Embase, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 31st, 2020. The search was not restricted to time or publication status. Outcomes included rates of long-term mortality (>7 year or longer).

Results

A total of 518 studies were resulted from literature search. A total of 14 studies and 204,223 patients; 158,663 men and 45,556 women, with a mean age of the men 60.2 years and 63.2 years for women, were included in our systematic review and meta-analysis. Our analysis suggested sex-related differences in long-term mortality (>7 years) following CABG (odds ratio (1), 1.15; 95% confidence interval (2), 1.017–1.30; P<.02).

Conclusions

Our results suggest that women had higher long-term mortality following CABG compared with men. It is the largest study to date of sex-specific differences in long-term mortality (>7 years).

Funding Acknowledgement

Type of funding sources: None. Meta-analysisDemographics
Reintervention for the trifecta aortic bioprosthesis: large single-centre series
Authors: Fard A , Al-Attar N
Published: October 2021

Introduction

Aortic valve replacement with the Trifecta aortic bioprosthesis has reported favourable haemodynamic performance. However, several reports of structural valve deterioration have raised concerns of design risks and its long-term durability.

Purpose

We conducted this study to assess reintervention and outcomes in a large single-centre cohort of 944 patients receiving the Trifecta valve over a 10-year period.

Methods

Consecutive patients undergoing aortic valve replacement with the Trifecta valve between October 2011 and October 2020 in our centre were included in this study. Perioperative patient and operative characteristics were prospectively recorded in an independent database. Reintervention was recorded as a surrogate for structural valve deterioration, and survival data was analysed.

Results

A total of 944 patient (mean age 72.82 years ± 8.13, range 28–91, 58% male) underwent aortic valve replacement with the Trifecta valve in our centre between October 2011 and October 2020. At 10-years, 1.4% of patients required a redo operation for aortic valve replacement, giving an overall freedom reintervention of 98.6%, with a 99.3% and 99.4% freedom from reintervention due to structural valve deterioration and infection, respectively. The mean time to all-cause reintervention was 48.87 months, and the mean time to reintervention due to SVD was 68.87 months. Patients that did not require reintervention had a 97.74% freedom from mortality and those that underwent reintervention had a freedom from mortality of 84.62% with a median survival of 69-days.

Conclusions

In a large single-centre cohort, the Trifecta aortic bioprosthesis was safe with a 1.4% all-cause reintervention rate and a 0.7% reintervention rate for structural valve deterioration at 10-years.

Funding Acknowledgement

Type of funding sources: None.
Comparison of deep learning with traditional models to predict preventable acute care use and spending among heart failure patients
Authors: Lewis M , Figueroa J
Published: October 2021

Recent health reforms have created incentives for cardiologists and accountable care organizations to participate in value-based care models for heart failure (HF). Accurate risk stratification of HF patients is critical to efficiently deploy interventions aimed at reducing preventable utilization. The goal of this paper was to compare deep learning approaches with traditional logistic regression (LR) to predict preventable utilization among HF patients. We conducted a prognostic study using data on 93,260 HF patients continuously enrolled for 2-years in a large U.S. commercial insurer to develop and validate prediction models for three outcomes of interest: preventable hospitalizations, preventable emergency department (ED) visits, and preventable costs. Patients were split into training, validation, and testing samples. Outcomes were modeled using traditional and enhanced LR and compared to gradient boosting model and deep learning models using sequential and non-sequential inputs. Evaluation metrics included precision (positive predictive value) at k, cost capture, and Area Under the Receiver operating characteristic (AUROC). Deep learning models consistently outperformed LR for all three outcomes with respect to the chosen evaluation metrics. Precision at 1% for preventable hospitalizations was 43% for deep learning compared to 30% for enhanced LR. Precision at 1% for preventable ED visits was 39% for deep learning compared to 33% for enhanced LR. For preventable cost, cost capture at 1% was 30% for sequential deep learning, compared to 18% for enhanced LR. The highest AUROCs for deep learning were 0.778, 0.681 and 0.727, respectively. These results offer a promising approach to identify patients for targeted interventions.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): internally funded by Diagnostic Robotics Inc.
Prostaglandin E1 attenuates AngII-induced cardiac hypertrophy via EP3 receptor activation and Netrin-1upregulation
Authors: Shen L , Shen Y , Wang X , He B
Published: October 2021

Aims

Pathological cardiac hypertrophy induced by activation of the renin–angiotensin–aldosterone system (RAAS) is one of the leading causes of heart failure. However, in current clinical practice, the strategy for targeting the RAAS is not sufficient to reverse hypertrophy. Here, we investigated the effect of prostaglandin E1 (PGE1) on angiotensin II (AngII)-induced cardiac hypertrophy and potential molecular mechanisms underlying the effect.

Methods and results

Adult male C57 mice were continuously infused with AngII or saline and treated daily with PGE1 or vehicle for two weeks. Neonatal rat cardiomyocytes were cultured to detect AngII-induced hypertrophic responses. We found that PGE1 ameliorated AngII-induced cardiac hypertrophy both in vivo and in vitro. The RNA sequencing (RNA-seq) and expression pattern analysis results suggest that Netrin-1 (Ntn1) is the specific target gene of PGE1. The protective effect of PGE1 was eliminated after knockdown of Ntn1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the PGE1-mediated signaling pathway changes are associated with the mitogen-activated protein kinase (MAPK) pathway. PGE1 suppressed AngII-induced activation of the MAPK signaling pathway, and such an effect was attenuated by Ntn1 knockdown. Blockade of MAPK signaling rescued the phenotype of cardiomyocytes caused by Ntn1 knockdown, indicating that MAPK signaling may act as the downstream effector of Ntn1. Furthermore, inhibition of the E prostanoid (EP)3 receptor, as opposed to the EP1, EP2, or EP4 receptor, in cardiomyocytes reversed the effect of PGE1, and activation of EP3 by sulprostone, a specific agonist, mimicked the effect of PGE1.

Conclusion

In conclusion, PGE1 ameliorates AngII-induced cardiac hypertrophy through activation of the EP3 receptor and upregulation of Ntn1, which inhibits the downstream MAPK signaling pathway. Thus, targeting EP3, as well as the Ntn1–MAPK axis, may represent a novel approach for treating pathological cardiac hypertrophy.

Funding Acknowledgement

Type of funding sources: None.
Sterile inflammation through Ca2+/ Calmodulin-dependent protein kinase II signaling is essential for adverse cardiac remodeling
Authors: Suetomi T , Okuda S , Okamoto Y , Tateda S , Uchinoumi H , Oda T , Kobayashi S , Yamamoto T , Yano M
Published: October 2021

Introduction and hypothesis

Sterile inflammation is associated with cardiac remodeling in response to non-ischemic stress, but how it is initiated in the absence of cell death and how it is propagated are not well elucidated. We tested the hypothesis that activation of CaMKII in cardiomyocytes and macrophages in response to pressure overload initiates inflammatory responses leading to adverse cardiac remodeling.

Methods and results

Cardiomyocyte specific CaMKIIδ knockout (CKO) mice were subjected to transverse aortic constriction (TAC). CaMKII and NFkB activation were significantly increased in control fl/fl (CTL) but not in CKO hearts. Cardiac mRNA levels for pro-inflammatory cytokines also increased vs sham. These responses were significantly attenuated in the CKO mice. Activated NLRP3 inflammasome was shown by elevated caspase-1 activity in isolated cardiomyocytes of CTL while attenuated in CKO. Macrophage accumulation was attenuated in the CKO and NLRP3 inhibitor MCC950 treated mice. Cardiac fibrosis and subsequent cardiac dysfunction were less impaired in the CKO vs CTL (ejection fraction 43±3% vs 33±5%). Upregulated NLRP3 gene expression, elevated CaMKII and caspase-1 activity were observed in neonatal mouse cardiomyocytes (NMCMs) in response to osmotic stretch. Increased caspase-1 activity was observed in macrophages cultured with media from osmotic-stretched NMCMs and it was attenuated by pretreatment of CaMKII inhibitor KN-93. Coincubation with stretched NMCMs induced inflammatory responses in isolated macrophages from wild-type mice but not in isolated macrophages from KN-93 pretreated mice.

Conclusions

Activated CaMKIIδ in response to pressure overload triggers inflammatory signals including NLRP3 inflammasome cascade in cardiomyocytes. CaMKII could also contribute amplification of inflammasome signal in macrophages leading fibrosis and consequent cardiac dysfunction. CaMKII in cardiomyocytes and macrophages could be a therapeutic target to prevent progression of non-ischemic heart failure.

Funding Acknowledgement

Type of funding sources: None.
A variant noncoding region regulates Prrx1 and predisposes to atrial arrhythmias
Authors: Bosada F M , Rivaud M R , Uhm J.-S , Verheule S , Van Duijvenboden K , Verkerk A O , Christoffels V M , Boukens B J
Published: October 2021

Rationale

Atrial Fibrillation (AF) is the most common cardiac arrhythmia diagnosed in clinical practice. Genome-wide association studies have identified AF-associated common variants across 100+ genomic loci, but the mechanism underlying the impact of these variant loci on AF susceptibility in vivo has remained largely undefined. One such variant region, highly associated with AF, is found at 1q24, close to PRRX1, encoding the Paired Related Homeobox 1 transcription factor.

Objective

To identify the mechanistic link between the variant region at 1q24 and AF predisposition.

Methods and results

The mouse orthologue of the noncoding variant genomic region (R1A) at 1q24 was deleted using CRISPR genome editing. Among the genes sharing the topologically associated domain with the deleted R1A region (Kifap3, Prrx1, Fmo2, Prrc2c), only the broadly expressed gene Prrx1 was downregulated in mutants, and only in cardiomyocytes. Expression and epigenetic profiling revealed that a cardiomyocyte lineage-specific gene program (Mhrt, Myh6, Rbm20, Tnnt2, Ttn, Ckm) was upregulated in R1A−/− atrial cardiomyocytes, and that Mef2 binding motifs were significantly enriched at differentially accessible chromatin sites. Consistently, Prrx1 suppressed Mef2-activated enhancer activity in HL-1 cells. Mice heterozygous or homozygous for the R1A deletion were susceptible to atrial arrhythmia induction, had atrial conduction slowing and more irregular RR intervals. Isolated R1A−/− mouse left atrial cardiomyocytes showed lower action potential upstroke velocities and sodium current, as well as increased systolic and diastolic calcium concentrations compared to controls.

Conclusion

The noncoding AF variant region at 1q24 modulates Prrx1 expression in cardiomyocytes. Cardiomyocyte-specific reduction of Prrx1 expression upon deletion of the noncoding region leads to a profound induction of a cardiac lineage-specific gene program and to propensity for AF. These data indicate that AF-associated variants in humans may exert AF predisposition through reduced PRRX1 expression in cardiomyocytes.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Fondation Leducq
Clinical and morphological characteristics of COVID-19-associated myocarditis
Authors: Kogan E A , Kukleva A D , Blagova O V , Berezovskij Y U S
Published: October 2021

Background

COVID-19 is accompanied by the development of a wide range of cardiovascular lesions. The goal: to study the clinical and morphological features of SARS-CoV-2-associated myocarditis (SCM), determining the presence of viral RNA and proteins in myocardial tissue.

Methods

The study was based on 32 autopsies with a confirmed diagnosis of myocarditis. The average age of the patients was 72.7±15.5 years. Men predominated in the group (53%). The immunohistochemical determination of the surface markers of CD45, CD3, CD20, CD 68 inflammatory infiltrates and SARS-CoV-2 nucleocapsid and spike protein has been done. Detection of coronavirus RNA was performed.

Results

The clinical manifestations SCM included heart failure and variety of rhythm disturbances. Increased level of anticardiac antibodies was detected. Lymphomacrophage infiltrates (more than 7 CD3+ T-lymphocytes, more than 14 CD45+ lymphocytes and more than 7 CD68+ macrophages per 1 mm2) were found in 100% of cases. RNA of the virus was detected in myocardial tissue. Virus proteins were identified in macrophages of the inflammatory infiltrate and cardiomyocytes.

Conclusion

The results suggest persistence of the virus in the myocardium and the development of chronic myocarditis.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Russian Foundation for Fundamental Research
Improvement of retinal microvascular function after initiation of lipid-lowering therapy with PCSK9 inhibitors – an observational study
Authors: Naegele M , Raemy Y , Barthelmes J , Kreysing L , Haider T , Ruschitzka F , Flammer A J , Sudano I
Published: October 2021

Background

Hypercholesterolemia is associated with endothelial dysfunction. While good evidence exists for the beneficial endothelial effects of first-line lipid-lowering drugs (statins), less is known on the new class of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. This is particularly true for the differential effects on micro- and macrovascular endothelial function and arterial stiffness.

Purpose

The goal of this study was to study the change in retinal microvascular dysfunction, brachial artery endothelial function and arterial stiffness in high-risk cardiovascular risk patients before and after initiation of PCSK9 inhibitor therapy with alirocumab or evolocumab.

Methods

In this prospective observational study, cardiovascular high-risk patients with a clinical indication for PCSK9 inhibitors were included for the measurement of retinal microvascular function (flicker light-induced dilatation of retinal arterioles and venules, FIDart and FIDven respectively; retinal arteriovenous ratio, AVR), brachial artery flow-mediated dilatation (FMD) and arterial stiffness (pulse wave velocity, PWV; augmentation index, AI). Measurements were performed at baseline, after 3 months and after 12 months of PCSK9 inhibitor therapy. The primary endpoint was the change in FIDart after 12 months of therapy compared to baseline.

Results

We recruited 48 patients (mean age 57±11 years, 27% female, 81% coronary artery disease) which began treatment with alirocumab or evolocumab in our lipid outpatient clinic. 6 patients were excluded from the analysis (n=3 stopped due to side effects, n=1 stopped due to new metastatic cancer, n=1 moved abroad, n=1 no retinal vessel analysis possible). LDL cholesterol was reduced from 3.8±1.2 to 1.5±0.8 and 1.8±0.9 mmol/L at 3 and 12 months respectively (all p<0.001). There was no significant change in systolic blood pressure during therapy. The primary endpoint FIDart was significantly increased after 12 months of PCSK9 inhibitor therapy compared to baseline (3.4±2.3 vs. 2.6±1.6%, p=0.01). Among the secondary endpoints, augmentation index improved at 12 months vs. baseline (21±12 vs. 24±9%, p=0.03). No significant change was seen for FIDven, AVR, FMD and PWV after 3 and 12 months of therapy.

Conclusion

In cardiovascular high-risk patients, PCSK9 inhibition is associated with an improvement of retinal microvascular function and augmentation index after one year of therapy. No effects were seen for macrovascular parameters such as FMD or PWV in our cohort.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): University Hospital Zurich, AGLA Grant (sponsored by Amgen)
Acetyl-CoA carboxylase inhibition alters tubulin acetylation and aggregation in thrombin-stimulated platelets
Authors: Octave M , Pirotton L , Ginion A , Robaux V , Lepropre S , Kautbally S , Darley-Usmar V M , Ambroise J , Guigas B , Giera M , Foretz M , Bertrand L , Beauloye C , Horman S
Published: October 2021

Introduction

Acetyl-CoA carboxylase (ACC), the first enzyme regulating lipid synthesis, promotes thrombus formation by increasing platelet phospholipid content. Inhibition of its activity decreases lipogenesis and increases the content in acetyl-CoA which can serve as a substrate for protein acetylation. This posttranslational modification plays a key role in the regulation of platelet aggregation, via tubulin acetylation.

Purpose

To demonstrate that ACC inhibition may affect platelet functions via an alteration of lipid content and/or tubulin acetylation.

Methods

Platelets were treated 2 hours with CP640.186, a pharmacological ACC inhibitor, prior to thrombin stimulation. Platelet functions were assessed by aggregometry and flow cytometry. Lipogenesis was measured via 14C-acetate incorporation into lipids. Lipidomics analysis was carried out on the commercial Lipidyzer platform. Protein phosphorylation and acetylation were evaluated by western blot.

Results

Treatment with CP640.186 drastically decreased platelet lipogenesis. However, the quantitative lipidomics analyses showed that preincubation with the compound did not affect global platelet lipid content. Interestingly, this short-term ACC inhibition was sufficient to increase tubulin acetylation level, at basal state and after thrombin stimulation. It was associated with an impaired platelet aggregation, in response to low thrombin concentration, while granules secretion was not affected. Mechanistically, we highlighted a decrease in Rac1 activity, associated with a reduced phosphorylation of its downstream effector PAK2. Surprisingly, actin cytoskeleton was not impacted but we evidenced a significant decrease in ROS production which could result from a decreased NOX2 activity.

Conclusion

Pharmacological ACC inhibition decreases platelet aggregation upon thrombin stimulation. The mechanism depends on increased tubulin acetylation, with subsequent alteration of the Rac1/PAK2/NOX2 signaling pathway

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Fonds pour la formation à la Recherche dans l'Industrie et l'Agriculture (FRIA)
Global magnitude and temporal trend of infective endocarditis, 1990–2019: results from the Global Burden of Disease Study
Authors: Yang Xiaorong , Chen Hui , Zhang Dandan , Shen Lin , An Guipeng , Zhao Shaohua
Published: October 2021

Aims

To estimate the spatiotemporal patterns in infective endocarditis (IE) burden along with its attributable risk factors at the national, regional, and global levels, which is essential to optimize the targeted prevention, clinical practice, and research.

Methods and results

Based on all available data sources, the incidence, mortality, and disability-adjusted life years (DALYs) of IE in 204 countries and regions from 1990 to 2019 were reconstructed by Global Burden of Disease Study 2019 using the Cause of Death Ensemble model, spatiotemporal Gaussian process regression, and DisMod-MR 2.1. We depicted the epidemiological characteristics of IE in detail by gender, region, and age. Globally, 1 090 527 incident cases, 66 322 deaths, and 1 723 594 DALYs of IE were estimated in 2019. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) increased from 9.91 and 0.73 to 13.80 and 0.87 per 100 000 person-years over the past 30 years, respectively. ASIR were consistently more pronounced in higher socio-demographic index (SDI) regions. The leading ASMR in 2019 appeared in the High SDI region, with the largest increase in the past three decades. The age-specific burden rate of IE among people over 25 years old usually increased with age, and the annual increasing trend was more obvious for people over 60 years of age, especially in higher SDI regions.

Conclusion

The incidence and mortality of IE have continued to rise in the past 30 years, especially in higher SDI regions. The patient population was gradually shifting from the young to the elderly.
Atrial-paced, exercise-similar heart rate envelope induces myocardial protection from ischaemic injury
Authors: Zhu Zhiyong , Gao Zhan , Chen Biyi , Hall Duane D , Minerath Rachel , Koval Olha , Sierra Ana , Subbotina Ekaterina , Zhu Xiaoyi , Kim Young Rae , Yang Jun , Grumbach Isabella , Irani Kaikobad , Grueter Chad , Song Long Sheng , Hodgson-Zingman Denice M , Zingman Leonid V
Published: October 2021

Aims

The study investigates the role and mechanisms of clinically translatable exercise heart rate (HR) envelope effects, without dyssynchrony, on myocardial ischaemia tolerance compared to standard preconditioning methods. Since the magnitude and duration of exercise HR acceleration are tightly correlated with beneficial cardiac outcomes, it is hypothesized that a paced exercise-similar HR envelope, delivered in a maximally physiologic way that avoids the toxic effects of chamber dyssynchrony, may be more than simply a readout, but rather also a significant trigger of myocardial conditioning and stress resistance.

Methods and results

For 8 days over 2 weeks, sedated mice were atrial-paced once daily via an oesophageal electrode to deliver an exercise-similar HR pattern with preserved atrioventricular and interventricular synchrony. Effects on cardiac calcium handling, protein expression/modification, and tolerance to ischaemia–reperfusion (IR) injury were assessed and compared to those in sham-paced mice and to the effects of exercise and ischaemic preconditioning (IPC). The paced cohort displayed improved myocardial IR injury tolerance vs. sham controls with an effect size similar to that afforded by treadmill exercise or IPC. Hearts from paced mice displayed changes in Ca2+ handling, coupled with changes in phosphorylation of calcium/calmodulin protein kinase II, phospholamban and ryanodine receptor channel, and transcriptional remodelling associated with a cardioprotective paradigm.

Conclusions

The HR pattern of exercise, delivered by atrial pacing that preserves intracardiac synchrony, induces cardiac conditioning and enhances ischaemic stress resistance. This identifies the HR pattern as a signal for conditioning and suggests the potential to repurpose atrial pacing for cardioprotection.