bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical roles of Parkin and PINK1 in antiviral immunity and protection from cell death in Enterovirus-induced viral myocarditis
Authors: Jin U , Park S J , Park S M
Published: October 2022

Background

Myocarditis is an inflammatory disease of the heart muscle often resulting in cardiac dysfunction and death. One of the most common causes is a cardiac infection with viruses, especially with enteroviruses of the Coxsackievirus B (CVB) family. CVB3-induced viral myocarditis is a well-established model to elucidate viral myocarditis in mice. It is assumed that mitochondrial damage control and mitochondria-associated innate immunity is essential for defence against viral infection of the heart muscle. And Parkinson's disease genes Parkin and PINK1 are well known for their critical function in mitochondrial homeostasis and damage control. We investigated the roles of Parkin and PINK1 in CVB3-induced viral myocarditis mouse model.

Material and methods

Male C57BL/6J WT, Parkin KO and PINK1 KO mice were used in an age of 8 to 12 weeks. The animals were injected intraperitoneally with 1x104 plaque forming units of CVB3 diluted in phosphate-buffered saline. Control and survived virus-infected mice were sacrificed for tissue sampling at day 7 to investigate imaging and molecular workup.

Result

After virus inoculation, the Parkin KO and PINK1 KO groups showed a significantly lower 28-day survival rate compared with the WT group (p<0.001 in Parkin KO; p<0.001 in PINK1 KO). Evans-Blue Dye (EBD) staining image of day 7 after virus-infection showed that the hearts of Parkin KO and PINK1 KO mice were more severely damaged than the hearts of WT mice (3.2-fold, p<0.01 in Parkin KO; 2.6-fold, p<0.05 in PINK1 KO). H&E staining showed that severe inflammatory reaction occurred in the hearts of WT mice, although the inflammatory reaction was much lower compared to WT in the hearts of Parkin KO and PINK1 KO mice (p<0.001 in Parkin KO; p<0.001 in PINK1 KO). In immunohistochemistry, EBD staining positive area colocalized well with CVB3 in Parkin KO and PINK1 KO mice hearts, although EBD staining positive area was rare and didn't colocalized well CVB3 in WT mice hearts. mRNA levels of cell markers (CD3, natural cytotoxicity receptors, F4/80), inflammatory cytokines (IL-1β, IL-6, TNF-α), type II interferon, macrophage-derived protective factors, and CXCL10 family cytokines were lower in virus-infected Parkin/PINK1 KO mice than WT mice. Western blots showed that phospho-p65 increased less than WT in the heart of Parkin KO (0.7-fold, p<0.05) and PINK1 KO mice (0.58-fold, p<0.05).

Conclusion

The Parkin KO and PINK1 KO mice showed a higher mortality rate and more severe cardiomyocyte damage than the WT mice in the viral myocarditis mouse model. Parkin and PINK1 is critical to the type II IFN pathway that inhibits virus replication. And Parkin and PINK1 play an important role in the recruitment of IFN-γ-producing lymphocytes through NF-κB pathway and CXCL10 family chemokines.

Funding Acknowledgement

Type of funding sources: None.
Intracardiac echocardiography-guided left atrial appendage occlusion: descriptive analysis
Authors: Grazina A , Cardoso I , Viegas J M , Albuquerque F , Ferreira A , Santos A R , Teixeira B , Ferreira V , Fiarresga A , Ramos R , Cacela D , Moura Branco L , Galrinho A , Cruz Ferreira R
Published: October 2022

Introduction

Oral anticoagulants are the standard treatment for prevention of stroke in patients with atrial fibrillation (AF). However, some patients still have stroke despite anticoagulation or have contraindications to anticoagulation. The left atrial appendage occlusion (LAAO) is an option for those patients. The use of intracardiac echocardiography (ICE) instead of Transesophageal echocardiography guiding LAAO procedures has increased, allowing to reduce the use of general anesthesia.

Objectives

The aim of this study is to describe data regarding safety and efficacy in patients submitted to ICE-guided LAAO.

Methods

In a tertiary center, patients submitted to ICE-guided LAAO were identified. Information regarding baseline characteristics, procedure technical success, complications, hospitalization and follow-up data was noted retrospectively. The registered stroke and bleeding rates were compared with predicted rates using CHA2DS2-VASc and HAS-BLED scores, respectively.

Results

45 patients underwent ICE-guided LAAO, mean age 75.5±9.6 years old, 71.1% male (detailed characteristics in table 1). Permanent AF was present in 68.9% (n=31), with average CHA2DS2-VASc and HAS-BLED scores of 4.0±1.4 and 3.6±1.1, respectively (predicting a stroke risk of 4.0% per year and a major bleeding risk of 8.7% per year). The LAAO indication was previous major bleeding in 64.4% (n=29), high bleeding risk in 24.4% (n=11) and embolic events despite therapeutic anticoagulation in 11.1% (n=5). The LAAO devices were implanted successfully in 96% of the patients (n=43). It was noted a complication rate of 8.8% (n=4), perforation in 4.4% (n=2), device embolization in 4.4% (n=2, one of them leading to cardiac arrest and death) and no major vascular complications occurred. No other procedure-related deaths occurred. The average duration of hospitalization after the procedure was 5.7 days. All patients were followed-up for a mean period of 19.0 months. During that period, another death (2.2%) occurred with a non-cardiac cause and the re-hospitalization rate was 26.7% (n=12), 11.1% (n=5) for cardiac causes. During the same period, 1 stroke (2.2%) and 6 major bleeding (13.3%) occurred – yearly rates of 1.4% and 8.4%, respectively. The stroke rate is markedly inferior to predicted by the score and the major bleeding is slightly inferior to predicted.

Conclusions

This study provides data about the safety and mainly about the efficacy of the LAAO guided by ICE in a cohort of patients with high hemorrhagic and embolic risk.

Funding Acknowledgement

Type of funding sources: None.
In-hospital glycemic variability and all-cause mortality in patients hospitalized with acute heart failure: analysis of the KorAHF registry
Authors: Chun K H , Oh J , Lee C J , Kang S M
Published: October 2022

Introduction

Glycemic variability (GV) is known to be a poor prognostic marker in various diseases including cardiovascular disease.

Purpose

We investigated the association of GV with all-cause mortality in patients with acute heart failure (HF).

Methods

The Korean Acute Heart Failure registry enrolled patients hospitalized for acute HF from 2011 to 2014. Among survivors of the index hospitalization, we analyzed those who had ≥3 blood glucose measurements before discharge. Patients were divided into two groups based on their coefficient of variation (%CV) as an indicator of GV. We investigated all-cause mortality at 6 month and 1 year after discharge.

Results

The study analyzed 2,617 patients (median age 72 years, 53% male). During the median follow-up period of 11 months, 583 (22%) patients died. Compared to alive patients, patients who died had a significantly higher diabetes prevalence (46% vs. 41%, P=0.035) and higher %CV (31.0% vs. 27.5%, P<0.001). Kaplan-Meier curve analysis revealed that a high GV (%CV >21%) was associated with lower cumulative survival to all-cause death compared with a low GV (%CV ≤21%) (log-rank P<0.001). Multivariate Cox proportional analysis showed that a high GV was associated with an increased risk of 6-month mortality (hazard ratio [HR] 2.02, 95% CI 1.58–2.59, P<0.001) and one-year mortality (HR 1.57, 95% CI 1.29–1.91, P<0.001). The risk of high GV for one-year mortality was significant in non-diabetic patients (HR 1.98, 95% CI 1.55–2.53, P<0.001), but not in diabetic patients (HR 1.24, 95% CI 0.91–1.69, P=0.176; P-for-interaction=0.030).

Conclusion

A high GV (%CV >21%) before discharge was associated with all-cause mortality within 1 year, especially in non-diabetic acute HF patients.

Funding Acknowledgement

Type of funding sources: None.
Derivation and validation of a machine learning-based risk prediction model for in-hospital mortality in patients with acute heart failure
Authors: Misumi K , Matsue Y , Nogi K , Kitai T , Oishi S , Suzuki S , Yamamoto M , Kida T , Okumura T , Nogi M , Ishihara S , Ueda T , Kawakami R , Saito Y , Minamino T
Published: October 2022

Background

Although risk stratification is important in patients with acute heart failure (AHF) to predict patient prognosis, pre-existing risk models have not often been used due to its complexity. Recently, machine learning methods have been presented as an alternative approach to analyzing the predictive probability of large clinical datasets.

Purpose

The aim of this study is to develop a user-friendly risk score developed by one of machine learning methods and compare the performance of the new risk score to the existing conventional risk models.

Methods

A machine-learning-based risk model was developed using least absolute shrinkage and selection operator (LASSO) regression by identifying predictors of in-hospital mortality in the derivation cohort (REALITY-AHF) and externally validating and comparing its performance with two pre-existing risk models: the Get With The Guidelines risk score incorporating brain natriuretic peptide and hypochloremia (GWTG-BNP-Cl-RS) and the acute decompensated heart failure national registry (ADHERE) risk model.

Results

In-hospital deaths in the derivation and validation (NARA-HF) cohorts were 76 (5.1%) and 61 (4.9%), respectively. The risk score comprised four variables (systolic blood pressure, blood urea nitrogen, serum chloride, and C-reactive protein) and was developed according to the results of the LASSO regression weighting the coefficient for selected variables using a logistic regression model (4V-RS). Even though 4V-RS comprised fewer variables, In the validation cohort, it showed a higher area under the receiver operating characteristic curve (AUC) than the ADHERE risk model (AUC, 0.783 vs. 0.740; P=0.059) and a significant improvement in net reclassification (0.359; 95% CI, 0.10–0.67; p=0.006). 4V-RS performed similarly to GWTG-BNP-Cl-RS in terms of discrimination (AUC, 0.783 vs. 0.759; p=0.426) and net reclassification (0.176; 95% CI, −0.08–0.43; p=0.178).

Conclusions

The 4V-RS model comprising only four readily available data points at the time of admission performed similarly to the more complex pre-existing risk model in patients with AHF.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Cardiovascular Research Fund
Tissue inhibitor of metalloproteinase (TIMP)-1 predicts negative remodeling and recovery of ejection fraction in acute heart failure with reduced ejection fraction
Authors: Tseng C H , Huang W M , Sung S H
Published: October 2022

Background

Heart failure with recovered ejection fraction (HFrecEF) is a recently identified phenotype of heart failure, which had lower rates of mortality, heart failure hospitalization, ventricular assist device placement, and heart transplantation compared to heart failure with reduced ejection fraction (HFrEF). Several predictors of HFrecEF had been proposed such as female gender, lower HF duration, nonischemic cause, no left bundle branch block (LBBB), lower EF, and lower N-terminal pro-brain natriuretic peptide (NT-proBNP) in the previous studies. Tissue inhibitors of metalloproteinase-1 (TIMP-1) was a biomarker that regulated the activity of metalloproteinases (MMPs). TIMP-1 was up-regulated during HF and was associated with ventricular remodeling and poor prognosis. However, the predictive value of TIMP-1 and MMP-9 in recovery of EF was yet to be investigated.

Purpose

The present study aimed at investigating the predictive value of TIMP-1 and MMP-9 of recovery of EF.

Methods

Subjects with acute decompensated heart failure and reduced left ventricular ejection fraction were eligible for this study. HFrEF was defined as EF <40% and HFrecEF was defined as follow-up EF ≥40% and ≥10% improvement from baseline EF. The biomarkers including NT-proBNP, plasma MMP-9 and serum TIMP-1 were measured in all enrolled subjects at admission. The receiver operating characteristic (ROC) curves and Youden index were used to select the model variables and cutoff values. Binary logistic regression analysis assessed the association between the biomarkers and recovery ejection fraction.

Results

Among a total of 91 AHF with reduced ejection fraction subjects (70.1±16.2 years, baseline EF 28.9±7.6%), 19 (20.8%) HFrecEF and 72 (79.2%) persistent HFrEF were found at 6 months. TIMP-1 and NT-proBNP were significantly higher in persistent HFrEF compared to HFrecEF. MMP-9 was similar between these two phenotypes of HF. The area under the ROC curve for recovery of ejection fraction of TIMP-1, MMP-9 and NT-proBNP were 0.69, 0.52, and 0.65, respectively. The optimal cutoff value of TIMP-1 according to Youden index was 200.68 ng/ml. In binary logistic regression analysis, TIMP-1 was negatively correlated with recovered ejection fraction as continuous variables [per 1-SD=8.96 ng/ml, odds ratio and 95% confidence interval: 0.99 (0.98–1.00)] and categorical variables [cutoff value 200.68 ng/ml, odds ratio and 95% confidence interval: 0.16 (0.05–0.54)] after adjusting age, gender, EF, acute myocardial infarction, LBBB and NT-proBNP.

Conclusions

In AHF subjects with HFrEF, TIMP-1 was negatively correlated to the recovery of EF and could be a potential biomarker for the prediction of the recovery of EF.

Funding Acknowledgement

Type of funding sources: None.
Dynamic right ventricular structural and functional changes in acute decompensated heart failure, new insights from serum sST2 and speckle-tracking echocardiography imaging
Authors: Kamal A , Darwish R , Abdel Hamid M , Hassan M
Published: October 2022

Background

Right ventricular (RV) mechanics are affected by volume/pressure overload in acute decompensated heart failure (ADHF) which can be detected using biomarkers and echocardiography. ST2 (suppression of tumorigenicity 2) is a biomarker of myocardial fibrosis and remodeling, that has been studied in patients with ADHF. Although baseline serum soluble ST2 (sST2) values at ADHF admission have been proved to predict outcomes, serial measurements are even of greater value.

Purpose

To evaluate the right ventricular dynamic structural and functional changes in ADHF patients during hospitalization, using serum sST2 and speckle-tracking echocardiography imaging.

Methods

We prospectively enrolled 61 ADHF patients with LV ejection fraction less than 50% and serum NT-proBNP more than 900 pg/ml. All patients received intravenous diuretics and did not require inotropic support during hospital stay. Blood samples were collected to measure serum sST2 levels on hospital admission and discharge. All patients underwent serial conventional and speckle tracking echocardiography on admission, at 48 hours and on hospital discharge. RV speckle tracking echocardiography analysis was done using 2D Cardiac Performance Analysis version 4.6.

Results

Serum sST2 had significant strong positive correlation with serum NT-proBNP on admission (r=0.84, P<0.0001) and showed significant reduction from 2.47 (1.27–4.05) ng/ml on admission to 1.86 (1.06–3.24) ng/dl at hospital discharge (P<0.0001) denoting successful decongestion. There was significant decrease in inferior vena cava diameter (P<0.0001) and estimated pulmonary artery systolic pressure (EPASP) (P=0.002) throughout hospital stay, however this was not associated with significant change in RV dimensions (P>0.05) or contractility assessed by trans-annular plane systolic excursion (TAPSE) (P=0.09) and S-wave velocity at lateral tricuspid annulus (P=0.9). There was significant improvement in RV free wall strain (RVFWS) (P=0.005) assessed by speckle tracking echocardiography which was mainly noticed after the first 48 hours till discharge, but RV 4-chamber strain (RV4CS) did not change significantly (P=0.06).

Conclusions

RVFWS assessed by speckle tracking echocardiography can detect improvement in RV systolic function not detected by other conventional echocardiographic parameters in ADHF patients. Improvement in RVFWS together with decline in serum sST2 levels can be used as marker of improved cardiac mechanics and successful decongestion.

Funding Acknowledgement

Type of funding sources: None.
Meta-analysis comparing the efficacy of dobutamine versus milrinone in acute decompensated heart failure and cardiogenic shock
Authors: Bandyopadhyay D , Malik A , Goel A , Biswas S , Hajra A , Gupta R , Lanier G , Naidu S
Published: October 2022

Objective

This study aims to evaluate the difference between dobutamine and milrinone in patients presenting with acute decompensated heart failure (AHF).

Background

Inotropes are indicated for treating AHF, especially in patients with concomitant hypoperfusion indicative of cardiogenic shock. However, previous studies have not identified the optimal inotrope. We sought to compare outcomes associated with milrinone versus dobutamine in patients with AHF.

Methods

A systematic literature search was performed to identify relevant trials from inception to August 2021. Our primary outcome of interest was mortality. Analysis was sub-categorized according to subpopulation, including AHF, AHF with cardiogenic shock (AHF-shock), AHF with a bridge to transplantation (AHF-BTT), and AHF with destination therapy (AHF-DT). Summary effects were calculated using a fixed-effects model as risk ratio or mean difference with 95% confidence intervals for all the clinical endpoints.

Results

Ten studies, including one randomized controlled trial with 21,106 patients, were included in the analysis (4918 patients were in the Milrinone group, while 15188 were in the Dobutamine group). Milrinone was associated with a lower risk of mortality in patients with AHF [relative risk (RR) 0.87; confidence interval (CI):0.79–0.97; p<0.05, heterogeneity I2=0%] with event rates of 9.4% vs. 9.8% [number needed to treat (NNT) of 250]. Milrinone was also associated with improved mortality with RR 0.76 (0.79–0.95; p<0.05) in patients with AHF-DT. There was a non-significant trend towards improved mortality in AHF-shock patients. However, AHF-BTT patients had a non-significant trend towards improved mortality with dobutamine. There was no difference between the two strategies for the outcomes of acute kidney injury, initiation of renal replacement therapy, mechanical ventilation, arrhythmias, symptomatic hypotension, and length of hospital stay (LOS) in the overall population. Intensive care unit (ICU) LOS was lower in AHF-shock patients in the milrinone group, whereas dobutamine was associated with a lower length of ICU stay in AHF patients.

Conclusion

The cumulative data comparing milrinone with dobutamine indicate an overall marginal benefit of milrinone compared to dobutamine in the totality of patients with AFH with or without cardiogenic shock, and whether or not they are bridged to transplantation or destination assist device. More appropriately powered prospective studies are needed to identify a conclusive benefit of one inotrope over another.

Funding Acknowledgement

Type of funding sources: None.
Pressure-strain loops unveil hemodynamics behind mechanical circulatory support systems
Authors: Landra F , Mandoli G E , Sciaccaluga C , Gallone G , Pica A , Cavigli L , D'Ascenzi F , Focardi M , Maccherini M , Bernazzali S , Valente S , Cameli M
Published: October 2022

Background

Mechanical circulatory support (MCS) systems are increasingly employed in critical hemodynamic states, such as in cardiogenic shock and end-stage heart failure. A thorough understanding of the complex interactions occurring between heart, vasculature and device is essential to optimize patient's management.

Purpose

This study aimed to explore the hemodynamic profile of patients under MCS using a non-invasive method based on pressure-strain analysis.

Methods

Consecutive patients admitted to the cardiological intensive care unit (CICU) from August 2021 to January 2022 undergoing different MCS systems positioning/implantation were retrospectively reviewed. Patients without a useful echocardiographic exam and/or arterial blood pressure invasive measurement at the time of echocardiography were excluded. Myocardial work analysis by Speckle Tracking Echocardiography (STE) was performed in these patients.

Results

3 patients with intra-aortic balloon pump (IABP), 2 patients with durable left ventricular assist device (dLVAD), 2 patients with temporaneous left ventricle (LV)-to-aortic pump, 1 patient with extracorporeal membrane oxygenation (ECMO) and 1 patient with ECMO and IABP were included. The use of IABP shifted the pressure-strain curve rightward and downward. Global work index (GWI) and global wasted work (GWW) decreased after IABP positioning, whereas global work efficiency (GWE) increased. The use of continuous-flow LV-to-aortic pumps, whether temporaneous or long-term (dLVAD), induced a significant change in the pressure-strain loop, with a shift towards a triangular shape. ECMO positioning alone resulted in a narrowing of the pressure-strain loop, with a decrease in GWI and GWE and an increase in GWW and mean arterial pressure. The combined used of IABP with ECMO widened the pressure-strain loop and improved GWI and GWE.

Conclusions

Pressure-strain loops unveil hemodynamic variations induced by mechanical circulatory support systems. Thus, myocardial work could be used to monitor ventricular-arterial-device coupling in such patients and therefore guide tailored management.

Funding Acknowledgement

Type of funding sources: None.
Differences in microRNA expression in pericoronary tissue adjacent to atherosclerotic plaque and from lesion-free coronary artery
Authors: Marketou M , Kontaraki J , Kalogerakos P , Plevritaki A , Pateromichelakis T , Kassotakis S , Maragkoudakis S , Kampanieris E , Zervakis S , Savva E , Mpantouvakis G , Lazopoulos G , Kochiadakis G
Published: October 2022

Background

Pericoronary adipose tissue (PCAT) plays a key role in the pathogenesis of atherosclerosis. PCAT is a source of microRNAs (miRs) that acts as messengers for intercellular communication. In this study, we investigated whether the PCAT surrounding coronary occlusive atherosclerotic lesions shows specific miR expression patterns compared to PCAT surrounding plaque-free segments.

Purpose

To evaluate the expression of miRs that are known to be implicated in the pathophysiology of atherosclerosis.

Methods

We included 49 patients (38 men, age 65±9 years) with 3-vessel coronary artery disease, who underwent elective coronary bypass surgery. The PCAT was harvested from two sites: adjacent to an occlusive atherosclerotic coronary lesion, and a plaque-free segment. miR-133a, miR-21, miR-26b, miR-9 and miR-143 levels in PCAT cells were quantified by real-time reverse transcription polymerase chain reaction.

Results

miR-26b, miR-21 and miR-143 showed significantly greater expression in PCAT samples taken from around atheromatous plaque (154±295 versus 37±96, p=0.014, for miR-26b; 122±265 versus 29±79, p=0.014, for miR-21; and 181±356 versus 31±50, p=0.03, for miR-143) (Figure 1). In addition, the expression of miR-143, miR-26b and miR-21 in PCAT from atherosclerotic plaque showed robust positive correlations with body.mass index (r=0.451, p=0.001, r=0.41, p=0.03 and r=0.416, p=0.003 respectively),

Conclusions

Analysis of PCAT located in proximity to atherosclerotic plaque showed a different pattern of miR expression compared to PCAT in a plaque-free segment. Our findings open new perspectives for the role of PCAT in the pathophysiological mechanisms of atherosclerotic disease and should be further investigated.

Funding Acknowledgement

Type of funding sources: None.
Pressure- and 3D-derived coronary flow reserve with hydro-static pressure correction: a validation by intracoronary Doppler measurements
Authors: Tar B , Agoston A , Uveges A , Szabo G T , Szuk T , Komocsi A , Czuriga D , Csippa B , Paal G , Koszegi Z
Published: October 2022

Purpose

To develop a method of coronary flow reserve (CFR) calculation derived from three-dimensional (3D) coronary angiographic parameters and intracoronary pressure data during fractional flow reserve (FFR) measurement.

Methods

Altogether 19 coronary arteries of 16 native and 3 stented vessels were reconstructed in 3D. The measured distal intracoronary pressures were corrected to the hydrostatic pressure based on the height differences between the levels of the vessel orifice and the sensor position. Classical fluid dynamic equations were applied to calculate the flow during the resting state and vasodilatation on the basis of morphological data and intracoronary pressure values. 3D-derived coronary flow reserve (CFRp-3D) was defined as the ratio between the calculated hyperemic and the resting flow and was compared to the CFR values simultaneously measured by the Doppler sensor (CFRDoppler).

Results

Haemodynamic calculations using the distal coronary pressures corrected for hydrostatic pressures showed a strong correlation between the individual CFRp-3D values and the CFRDoppler measurements (r=0.89, p<0.0001). Hydrostatic pressure correction increased the specificity of the method from 46.1% to 92.3% for predicting an abnormal CFRDoppler <2.

Conclusions

CFRp-3D calculation with hydrostatic pressure correction during FFR measurement facilitates a comprehensive haemodynamic assessment, supporting the complex evaluation of macro- and microvascular coronary artery disease.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): University of Debrecen
Ventricular and vascular stiffening in ischemia with no obstructed coronary arteries: novel insight from pressure-volume analysis
Authors: Oneglia A P , Wei J , Samuels B , Jake Samuel T , Azarbal B , David Anderson R , Petersen J W , Cook-Weins G , Pepine C J , Noel Bairey Merz C , Nelson M D
Published: October 2022

Background

Ischemia with no obstructed coronary arteries (INOCA) is prevalent among women and associated with an increased risk of developing heart failure with preserved ejection fraction (HFpEF), however the mechanism linking these conditions remains poorly understood. Coronary vascular dysfunction is common in INOCA, representing a putative mechanism driving heart failure progression.

Purpose

To evaluate the role of coronary vascular dysfunction on left ventricular (LV) function in women with INOCA.

Methods

Women with suspected INOCA, defined as having signs and symptoms of ischemia but no obstructive coronary artery disease, underwent LV pressure-volume assessment at rest and during 3 minutes of isometric handgrip stress at 30% of maximal voluntary contraction. Coronary function testing was performed by infusing standard doses of adenosine, acetylcholine, and nitroglycerine through a guiding catheter placed in the left main coronary artery, per our published protocols. Using standardized definitions of normal versus abnormal responses, cases with zero abnormal coronary pathways (n=12) were compared to cases with three abnormal coronary pathways (n=7).

Results

At rest, end-systolic pressure and end-systolic elastance were elevated in cases with abnormal coronary vascular function (Figure), while normalized peak filling rate was lower (0.45±0.15 s mmHg–1 vs 0.37±0.08 s mmHg–1). With isometric handgrip, end-systolic pressure and end-systolic elastance increased similarly between groups, remaining highest in those with abnormal coronary vascular function (Figure). End-diastolic pressure-volume declined with handgrip in those without coronary vascular dysfunction, while increasing (up and to the left) in those with coronary vascular dysfunction (Figure). Likewise, normalized peak filling rate improved with handgrip in those without coronary vascular dysfunction, but did not change in those with coronary vascular dysfunction (0.66±0.37 s mmHg–1 vs 0.38±0.15 s mmHg–1).

Conclusions

We show heightened ventricular and vascular stiffness in women with INOCA who have abnormal coronary vascular function. These preliminary data support the hypothesis that coronary vascular dysfunction may be a putative mechanistic pathway driving heart failure progression in INOCA.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health
Relative monocytosis predicts the presence and severity of coronary artery disease on CT coronary angiography in patients with stable angina symptoms
Authors: Spray L , Beattie A , Spyridopoulos I
Published: October 2022

Background

Monocytes, among other leucocytes, are crucially involved in the pathogenesis of atherosclerosis, but the value of peripheral blood leucocyte counts in predicting the presence or absence of atherosclerotic coronary artery disease (CAD) is unknown.

Purpose

Investigating whether circulating counts of monocytes, lymphocytes and neutrophils predict CAD on computed tomography coronary angiography (CTCA) in patients presenting with stable chest pain.

Methods

All patients investigated with CTCA in our centre in the year 2021 were screened (n=1564). Patients presenting via the Rapid Access Chest Pain clinic were retrospectively identified, and those with a Full Blood Count from the 6 months prior to clinic were included (n=330). Traditional cardiovascular risk factors were ascertained from the clinic letter. CAD was defined as any epicardial stenosis >25% on CTCA. Patients with CAD were further classified as having either single or multivessel disease (left main stem disease was considered multivessel), and non-obstructive or obstructive disease (any stenosis >70% was considered obstructive).

Results

Patients with CAD had significantly higher mean monocyte count than those without CAD (0.61 vs. 0.55x109/L, p=0.004), while no differences were observed between groups in lymphocyte or neutrophil count. Monocyte count increased further with more severe CAD, being higher in patients with multivessel compared to single-vessel disease (0.62 vs. 0.60x109/L; p for trend including no CAD =0.012), and in patients with obstructive compared to non-obstructive disease (0.62 vs. 0.60x109/L; p for trend including no CAD=0.012).

The association between monocytes and CAD was most marked among patients with a history of hypercholesterolaemia (monocyte count in CAD vs. no CAD: 0.63 vs. 0.54x109/L, p=0.001), and was absent in those without (0.57 vs 0.56x109/L, p=0.695). In the hypercholesterolaemia subgroup (n=186), a forward conditional logistic regression model including monocyte count alongside traditional risk factors (age, sex, smoking status, diabetes mellitus, hypertension, cholesterol level and family history), showed that only increasing age (p<0.001), male sex (p<0.001) and increasing monocyte count (p=0.01) were independently predictive of CAD.

Conclusion

Raised monocyte count is associated with both the presence and severity of coronary artery disease in patients presenting with anginal symptoms. In patients with a history of hypercholesterolaemia, monocyte count had a more robust predictive ability than many traditional cardiovascular risk factors. Further work is needed to establish whether patients with a relative monocytosis have a higher cardiovascular risk than would be predicted by traditional risk tools.

Funding Acknowledgement

Type of funding sources: None.
Patterns and outcomes of cardiovascular emergency department encounters for men and women in the USA
Authors: Kobo O , Raisi-Estabragh Z , Elbadawi A , Velagapudi P , Sharma G , Petersen S E , Roguin A , Mamas M A
Published: October 2022

Aims

We described sex-differential disease patterns and outcomes of over 20.6 million cardiovascular emergency department (ED) encounters in the USA.

Methods and results

We analysed primary cardiovascular encounters from the Nationwide Emergency Department Sample (between 2016–2018). We grouped the documented cardiovascular diagnoses into 15 disease categories. The sample included 48.7% women; average age was 67 [54,78] years. Men had greater overall baseline co-morbidity burden; however, women had higher rates of obesity, hypertension, and cerebrovascular disease. For women, the most common ED encounters were essential hypertension (16.0%), hypertensive heart or kidney disease (14.1%), and atrial fibrillation (AF)/flutter (10.2%). For men, the most common encounters were hypertensive heart or kidney disease (14.7%), essential hypertension (10.8%), and acute myocardial infarction (AMI, 10.7%). Women were more likely to present with essential hypertension, hypertensive crisis, AF/flutter, supraventricular tachycardia, pulmonary embolism, or ischaemic stroke. Men were more likely to present with AMI or cardiac arrest. In logistic regression models adjusted for baseline covariates, women with intracranial haemorrhage had higher risk of hospitalisation and death. Women with ischaemic stroke had higher risk of hospitalisation and death in ED. Women presenting with pulmonary embolism were less likely to be hospitalised but were more likely to die. Women with aortic aneurysm/dissection had higher risk of hospitalisation and death. Men were more likely to die following presentations with hypertensive heart or kidney disease, AF/flutter, AMI, or cardiac arrest.

Conclusion

In this large nationally representative sample of cardiovascular ED presentations, we demonstrate significant sex differences in disease distribution, hospitalisation, and death.

Funding Acknowledgement

Type of funding sources: None.
Heme oxygenase-1 polymorphisms associate with ischemic cardiac complications and mortality in type 1 diabetes
Authors: Segersvard H , Forsblom C , Sandholm N , Harjutsalo V , Kosonen R , Laine M , Tikkanen I , Groop P H , Lakkisto P
Published: October 2022

Background/Introduction

Heme oxygenase-1 (HO-1), encoded by the HMOX1 gene is a highly inducible enzyme with multiple cardiovascular protective properties. Polymorphisms of the HMOX1 gene, especially a guanine-thymine dinucleotide repeat polymorphism (GTn), affects its transcriptional activity and is associated with cardiovascular complications in the general population.

Purpose

We studied the association of HMOX1 polymorphisms and HO-1 plasma levels with cardiovascular complications in patients with type 1 diabetes (DM1).

Methods

The study population consists of patients with DM1 participating in the nationwide, multicenter Finnish Diabetic Nephropathy Study (FinnDiane). We genotyped the HMOX1 GTn repeat (n=3990), extracted from genome-wide genotyping data two single nucleotide polymorphisms (SNPs) (−413A/T upstream variant rs2071746, and +99G/C p.Asp7Asn missense variant rs2071747; n=4278), and measured the plasma HO-1 levels (n=861) from blood samples taken during a regular visit to the study center. The GTn repeats were divided into short (S) and long (L) alleles where the cutoff point was L>29 repeats.

Results

In men, LL genotype was associated with ischemic cardiac events (LL 22.9% vs. SS/SL 17.0%, p=0.001, see figure) and mortality (p=0.031, see figure). The association was detected also when analyzing all patients (LL 19.5% vs. SS/SL 16%, p=0.006, see figure) but not women alone (LL 15.7% vs. SS/SL 14.9%, p=0.657). For −413A/T SNP, men with AA genotype had higher odds for ischemic cardiac events (21.0% vs. 17.4%, p=0.044, see figure) but no differences in women or all together were found. There were no differences between different genotypes of +99G/C for cardiovascular complications. There was no difference in HO-1 plasma levels between different genotypes (GTn repeat, −413A/T or +99G/C). Men had significantly higher HO-1 plasma levels compared to women (3.12±1.23 ng/l vs. 2.64±1.04 ng/l, p<0.001). Interestingly, in women, higher HO-1 plasma levels were associated with cardiovascular complications and the need for antihypertensive and lipid lowering medications.

Conclusions

In men, but not in women LL genotype of the HMOX1 GTn repeat and AA genotype of −413A/T SNP were associated with ischemic cardiac complications and mortality. Thus, HMOX1 genotype may influence the development of cardiovascular complications in DM1 patients in a gender-dependent manner.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): The Finnish Foundation for Cardiovascular ResearchFinnish State Funding for university-level research
Impact of BNP level in patients with heart failure on major bleeding events after percutaneous coronary intervention
Authors: Otsuka Y , Ishii M , Nakamura T , Tsujita K , Fujita H , Matoba T , Kohro T , Kabutoya T , Kario K , Kiyosue A , Mizuno Y , Nakayama M , Miyamoto Y , Sato H , Nagai R
Published: October 2022

Aims

The Academic Research Consortium for High Bleeding Risk (ARC-HBR) presents a bleeding risk assessment in antithrombotic therapy for patients post percutaneous coronary intervention (PCI). In Japanese patients, heart failure (HF), peripheral vascular disease, and frailty are established as bleeding risk factors in addition to ARC-HBR. However, it is unknown whether left ventricular function or severity of HF is associated with HBR. The aim of this study was to investigate the association between the severity of HF measured by BNP and future bleeding events after PCI.

Methods

Clinical Deep Data Accumulation System (CLIDAS), a multicenter database with 7 tertiary medical hospitals in JAPAN, was developed to collect data directly for patient characteristics, medications, laboratory test, physiological test, cardiac catheterization and PCI treatment in electronic medical records using Standardized Structured Medical Information eXchange Extended Storage (SS-MIX). This retrospective analysis using CLIDAS database included 7160 patients who underwent PCI during April 2014 and March 2020 in the participating hospitals and also who have completed 3-year follow-up were divided into two groups: No HF (n=6645) and HF (n=515). HF patients were furthermore divided based on high BNP (≥100 pg/ml) group (n=384) and low BNP (<100 pg/ml) group (n=131). Primary outcome was defined as bleeding events according to the moderate and severe bleeding in the GUSTO classification. In addition, secondary endpoint was major adverse cardiovascular events (MACE) defined as a composite of cardiac death, myocardial infraction and stroke.

Results

Multivariable Cox regression adjusted for age, sex, BMI, acute coronary syndrome, hypertension, diabetes, dyslipidemia, chronic kidney disease, hemodialysis, previous PCI, previous coronary artery bypass grafting, prior myocardial infraction, prior stroke, prior atrial fibrillation, prior PVD, left main trunk disease, multivessel disease, and anticoagulants use showed that HF with high BNP was significantly associated with bleeding events (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.10–2.50), MACE (HR, 2.16; 95% CI, 1.60–2.90), and all-cause death (HR, 1.74; 95% CI, 1.30–2.33), but not HF with low BNP.

Conclusions

The CLIDAS real-world database revealed that HF with high BNP was associated with future bleeding events, suggesting that bleeding risk might be altered depending on severity of HF.

Funding Acknowledgement

Type of funding sources: None.
Association of lipoprotein(a) levels with all-cause mortality following percutaneous coronary intervention
Authors: Dykun I , Hendricks S , Babinets O , Al-Rashid F , Totzeck M , Rassaf T , Mahabadi A A
Published: October 2022

Background

Although lipoprotein(a) (Lp(a)) is a causal genetic risk factor for atherosclerotic cardiovascular disease, the prognostic value of elevated Lp(a) in coronary artery disease (CAD) patients is inconsistent in previous studies. The precise impact of Lp(a) itself on all-cause mortality in addition to the changes in low-density lipoprotein cholesterol (LDL-C) levels remains uncertain.

Purpose

We tested the hypothesis that Lp(a) levels in CAD patients is associated with long-term mortality, and such an association can by modified by LDL-C levels.

Methods

The present analysis is based on the longitudinal ECAD registry of consecutive patients undergoing coronary angiography with percutaneous revascularization therapy at the West German Heart and Vascular Center between 2004 and 2019. Lp(a) was quantified at hospital admission using a particle-enhanced immunonephelometric method. The incidence of death due to any cause was evaluated during follow-up. Cox regression analysis was used to determine the association between Lp(a) and all-cause mortality, adjusting for age, sex, LDL-C, smoking status, and family history of premature cardiovascular disease.

Results

Among 4941 patients (mean age 66.4±11.5 years, 77.8% male), median Lp(a) was 16 (7; 56) mg/dL and 1817 (36.8%) patients had elevated Lp(a) levels (≥30 mg/dl). During a median follow-up 3.1 years, 604 patients (12.2%) died. In multivariable Cox regression analysis, elevated Lp(a) was associated with an increased risk of all-cause mortality (Hazard ratio (HR): 1.23, [95% confidence interval (CI): 1.04; 1.45] p=0.01). When stratified by LDL-C category, only patients with LDL-C ≥100 mg/dL showed a significant association between Lp(a) and higher all-cause mortality (HR: 1.47; [1.16, 1.19], p<0.001), whereas Lp(a) levels were not linked with adverse prognosis, if LDL was better controlled (LDL<100mg/dl: 1.00; [0.79, 1.26], p=0.98).

Conclusions

In a large longitudinal registry cohort of patients with CAD undergoing invasive coronary angiography, elevated Lp(a) was associated with increased long-term mortality. LDL-C control seem to interact with the impact of Lp(a) levels on the patient's prognosis following percutaneous revascularization therapy.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only.
The role of conventional echocardiographic parameters on detecting subclinical anthracycline therapy related cardiac dysfunction
Authors: Zhang W , Azibani F , Libhaber E , Nankabirwa J , Okello E , Kayima J , Ssinabulya I , Sliwa K
Published: October 2022

Background

Subclinical anthracycline therapy related cardiac dysfunction (ATRCD) can be detected with speckle tracking echocardiographic image (STE), which is not widely available in Uganda. We aimed to investigate the accuracy, sensitivity and specificity of the two conventional echocardiographic parameters (reduction of mitral annular plane systolic exertion (MAPSE) and reduction of mitral annular peak systolic tissue Doppler velocity (s')) on diagnosing subclinical ATRCD.

Method and results

207 cancer patients who underwent anthracycline based chemo therapy were recruited at baseline and followed up until 6 months after ending anthracycline therapy. Comprehensive echocardiographic data were collected at each visits. Global longitudinal strain (GLS) by STE was used as the gold standard diagnostic test to define the case of subclinical ATRCD. Data of the 200 patients who had no evidence of clinical ATRCD were analyzed. 172 (86.0%) were female, with a median age of 42 years and cumulative incidence of ATRCD at the end of anthracycline therapy was 23.5% by GLS criteria. The AUC, cutpoint, sensitivity, specificity, PPV and NPV of reduction of MAPSE were 0.6736 (95% CI: 0.5885, 0.7587), ≥2 mm, 74.47% (95% CI: 59.65%, 86.06%), 54.90% (95% CI: 46.66%, 62.95%), 33.70% (95% CI: 24.68%, 43.58%) and 87.50%% (95% CI: 79.18%, 93.37%). The AUC, cutpoint, sensitivity, specificity, PPV and NPV of reduction of S' were 0.6018 (95% CI: 0.5084, 0.6953), ≥0.5 mm/s, 61.70% (95% CI: 46.38%, 75.49%), 52.67% (95% CI: 44.36%, 60.87%), 29.00% (95% CI: 20.36%, 38.93%) and 76.14%% (95% CI: 72.27%, 88.62%).

Conclusion

The reduction of MAPSE and S' demonstrated fairly good accuracy, sensitivity and negative predictive value to detect subclinical ATRCD in Ugandan cancer patients. These conventional echocardiographic parameters may serve as screening tools for detecting subclinical ATRCD in resource limited settings.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): NURTURE Research Training and Mentoring Program for Career Development of Faculty at MakerereUniversity College of Health Sciences, Uganda supported by the Office Of The Director, National Institutes of Health, National Institute of Dental and Craniofacial Research, National Institute Of Neurological.
Home care provision and nursing home admission after myocardial infarction in relation to cardiogenic shock and out-of-hospital cardiac arrest status
Authors: Dam Lauridsen M , Rorth R , Butt J H , Schmidt M , Kristensen S L , Kragholm K , Johnsen S P , Moller J E , Hassager C , Kober L V , Fosbol E L
Published: October 2022

Background

Autonomy is of great importance for quality of life. There is a paucity of data on autonomy for those who survive myocardial infarction (MI) with and without cardiogenic shock (CS) and out-of-hospital arrest (OHCA).

Purpose

To examine the association between CS, OHCA, and need for home care provision or nursing home admission as a proxy for impaired autonomy in a first-time MI population.

Methods

Danish nationwide registries were used to identify patients with first-time MI (2009–2019), who prior to the event were living at home without home care and discharged alive. The patients were stratified according to CS and OHCA status. We report 1-year cumulative incidence of a composite outcome of home care provision or nursing home admission with competing risk of death and as a secondary outcome all-cause mortality. Cause specific Cox regression models were used to estimate adjusted hazard ratios (HR) with patients without CS or OHCA as reference.

Results

We identified 61,451 patients in the period with MI (by groups: −OHCA/−CS: 59,316, −OHCA/+CS: 1,597, +OHCA/−CS: 913, and +OHCA/+CS: 669). The 1-year cumulative incidences of home care/nursing home were 6.9% for patients with −OHCA/−CS, 21.1% for −OHCA/+CS, 5.2% for +OHCA/−CS, and 8.1% for those with +OHCA/+CS. With the −OHCA/−CS as reference, the adjusted HRs for home care/nursing home were 3.12 (95% CI: 2.78–3.49) for patients with −OHCA/+CS, 1.27 (95% CI: 0.95–1.70) for +OHCA/−CS, and 2.31 (95% CI: 1.76–3.03) for +OHCA/+CS (Figure). The 1-year cumulative incidences of mortality were 4.8% for patients with −OHCA/−CS, 10.0% for −OHCA/+CS, 2.8% for +OHCA/−CS, and 3.7% for those with +OHCA/+CS (adjusted HRs: 2.81 (95% CI: 2.55–3.10), 1.09 (95% CI: 0.85–1.39) and 1.81 (95% CI: 1.42–2.30) (Figure 1).

Conclusion

In a selected cohort of patients with MI, without previous need for home care/nursing home and surviving until discharge date, patients with CS were independent of OHCA status associated with less autonomy after discharge with a more than two-fold higher 1-year incidence of home care provision or nursing home admission. Further, patients with CS were associated with a two-fold higher 1-year mortality compared with MI patients without CS independent of OHCA status.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): The work was supported by Rigshospitalets Research Foundation, Master cabinetmaker Sophus Jacobsen and Wife Astrid Jacobsen Foundation, and Director Jacob Madsen and Wife Olga Madsens Foundation. The funding source had no role in the design, conduct, analysis, or reporting of the study.