bluuebunny/crossref_metadata_2025 huggingface dataset:
Heart transplantation and antibody-mediated rejection: role of myocardial strain as an early marker of cardiac dysfunction in patients with anti-HLA antibody
Authors: Sciaccaluga C , Natali B.M , Mandoli G.E , Sisti N , Righini F.M , Menci D , D'Errico A , Benfari G , D'Ascenzi F , Cavigli L , Focardi M , Valente S , Bernazzali S , Maccherini M , Cameli M
Published: October 2021

Background

Antibody-mediated rejection of the transplanted heart is still currently diagnosed by endomyocardial biopsy whereas clinical elements, anti-Human Leukocite Antigens (HLA) antibody and graft dysfunction represents supplementary components.

Purpose

The aim of the study was to identify though a non-invasive imaging technique, such as advanced transthoracic echocardiography, early signs of altered cardiac function in patients with anti-HLA antibodies and no histological signs of antibody-mediated rejection.

Methods

The study population included 117 heart transplanted patients, in whom both acute and chronic rejection was excluded. They were divided into two groups “HLA+`' (45 patients) and “HLA−” (72 patients), based on the presence and the absence of circulating anti-HLA antibodies, respectively. The echocardiographic exam was performed within one week from the biopsy, including Speckle Tracking analysis.

Results

Deceleration Time of E wave was the strongest traditional echocardiographic parameter which correlated with circulating anti-HLA antibodies (165±39,5 vs 196,5±25; p<0.001). Regarding strain analysis, both left ventricular global longitudinal strain (−16,1±3,4 vs −19,8±2,0; p<0.001) and right ventricular strain (−17,2±0,7 vs −20,6±0,5; p=0.0002) differed significantly between the two subgroups (Figure 1). On the other hand, neither peak atrial longitudinal strain nor peak atrial contraction strain showed a significant correlation with anti-HLA antibodies.

Conclusion

The presence of circulating anti-HLA antibodies seems to be correlated with a mild cardiac dysfunction, even in the absence of antibody-mediated rejection. This subtle dysfunction is not completely detectable by standard echocardiographic parameters, whereas strain analysis has showed promising results since it revealed more clearly an impaired function of both ventricles in heart transplanted HLA+ patients, with potentially important clinical repercussion.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Outcomes of diabetic patients with end-stage heart failure listed for heart transplantation: a propensity-matched analysis
Authors: Akintoye E , Alvarez P , Briasoulis A
Published: October 2021

Background

There are on-going concerns about offering heart transplants to patients with diabetes due to the risk of poor outcomes. We investigated the current trends and outcomes of patients listed for heart transplants in the U.S. and provided a method for risk-stratification.

Methods

Using data from the United Network for Organ Sharing (UNOS), we identified heart failure patients listed for heart transplants between 2010 and 2019. Diabetic patients were propensity-matched with non-diabetes, and waitlist mortality as well as post-transplant graft survival were compared between the two matched groups. Further risk-stratification of the diabetic cohort was done based on the risk factors that independently predict the risk of graft failure.

Results

28,928 adult patients (30% diabetic) with end-stage heart failure were added to the waitlist over the study period. In the propensity-matched cohort, waitlist mortality was higher with diabetics compared to non-diabetics: 19.3 vs 17.1 deaths per 100 person-years, respectively, (HR=1.13 (95% CI=1.04–1.22, p=0.002). Over the study period, 5739 diabetics (mean age 57.6 years, 21.9% female) were transplanted. A total of 1308 (23.3%) and 1143 (20.4%) graft failures occurred in diabetic and non-diabetic recipients, respectively. Compared to non-diabetics, diabetics experienced worse graft survival (HR=1.17, 95% CI=1.08–1.26, p<0.001). We developed a risk score based on the 12 risk factors/markers that independently predict worse graft survival and a risk score of 4 reasonably differentiates between low and high-risk diabetics. Low risk diabetics (score≤4) had similar graft survival as non-diabetics with 1- and 5-year survival of 92.7% and 80.5%, respectively, (HR=0.91, 95% CI=0.82–1.01, p=0.06). On the other hand, high-risk diabetics had worse graft survival compared to non-diabetics (HR=1.52, 95% CI=1.38–1.67, P<0.001) with 1- and 5-year graft survival of 86.8% and 69.8%, respectively.

Conclusion

Diabetic patients with end-stage heart failure listed for heart transplantation experience higher waitlist mortality and worse post-transplant graft survival compared to non-diabetics. However, a simple risk score can be used for further risk-stratification in these patients to maximize survival benefit.

Funding Acknowledgement

Type of funding sources: None.
Hydration status, BMI and troponin as factors of an impaired exercise tolerance in women over 40 with arterial hypertension
Authors: Bielecka-Dabrowa A.M , Gryglewska K , Sakowicz A , Janikowski K , Maciejewski M , Banach M
Published: October 2021

Purpose

The aim was to identify factors influencing maximal oxygen uptake (VO2max) and early identification of hypertensive women at risk of heart failure (HF).

Methods

The 185 consecutive females with controlled hypertension were divided according VO2max quartiles. The patients underwent echocardiography, non-invasive body mass analysis, spiroergometry and hemodynamic parameters. Regression analyses determined predictors of the lowest VO2max (quartile 1: VO2max <17 ml/kg/min).

Results

Females with the worst oxygen consumption had significantly higher level of high sensitive cardiac Troponin T (hs-cTnT) [p=0.001], higher values of the left atrial (LA) volume, late diastolic mitral annulus velocity (A'), ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion (E/E') [p=0.0003, p=0.02, p=0.04; respectively] and lower E' [p=0.001] compared to controls. Women with the worst exercise capacity had higher body mass index (BMI) and fat content (kg and %) [p<0.0001], higher fat free mass (FFM) (kg) [p<0.0001], higher total body water content (TBW) [p=0.0002] as well as extracellular body water content (ECW) [p<0.0001] and intracellular body water content (ICW) [p=0.005], ECW/TBW x 100% [p<0.0001] and metabolic age [p<0.0001] compared to counterparts. In a multiple logistic regression model independently associated with VO2max were: ECW/TBW x 100% (OR 4.45, 95% CI: 1.77–11.21; p=0.002) Figure 1, BMI (OR 7.11, 95% CI: 2.01–25.11; p=0.002) Figure 2 and hs-cTnT level (OR 2.69, 95% CI: 1.23–5.91; p=0.013).

Conclusions

High-sensitivity cardiac troponin may serve as early biomarker of heart failure in hypertensive women. Hydration status should be considered in overall hypertensive women care. There is an importance of body mass compartments analysis in early identification of hypertensive females at risk of heart failure.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Project is financed by the Polish National Agency for Academic Exchange under the Foreign Promotion Programme. Figure 1Figure 2
Peritoneal dialysis as a therapeutic solution in elderly patients with cardiorenal syndrome and heart failure: a case-series report
Authors: Chrysohoou C , Magkas N , Kapota A , Bougatsos G , Kopelias J , Bliouras N , Petras D , Tsioufis K
Published: October 2021

Background

The aim of this work was to evaluate the impact of peritoneal dialysis (PD) on venous congestion, right ventricle function, systolic arterial pulmonary pressure and clinical functional status in elderly patients with cardiorenal syndrome (CRS) and chronic heart failure (HF).

Methods

A case series of 21 (17 males, 70±11 years) consecutive pts with diuretic-resistance heart failure and right ventricular dysfunction (median renal failure duration (RF) 60 months, range 13–287 months, mean ejection fraction 36±11%) having been engaged in PD (median of 12.5 months, range 2–28); 77% of the pts were under Automated Peritoneal Dialysis (APD), whereas the rest were under Continuous Ambulatory PD (CAPD). Patients' Pulmonary Artery Systolic Pressure (PASP), Central Venus Pressure (CVP) – through compression sonography – and body weight were evaluated in 6 intermediate clinical visits.

Results

During the follow-up period, the mortality rate was 8 deaths out of 21 pts (38%) (or 3 deaths/100 person-months).A significant reduction by 29.9% in PASP levels (p=0.013)and by 42% in CVP levels (p<0.001), and in right ventricular function was observed; whereas pts weight increased by 3.7% (p=0.001). NYHA class improved in 12 pts; whereas, in the rest pts remained constant (p=0.046). In 8 pts complications were reported (mainly presence of staphylococcus. aureus).

Conclusion

PD seems to confer a substantial benefit in clinical status, in line with improvement in venous congestion and right ventricle systolic pressure among elderly HF patients with CRS.

Funding Acknowledgement

Type of funding sources: None.
Long-term evolution of estimated glomerular filtration rate in heart failure
Authors: Codina Verdaguer P , Buchaca D , Spitaleri G , Domingo M , Santiago-Vacas E , Cediel G , Zamora E , Santesmases J , Troya M.I , Escabia C , Gonzalez B , Rivas C , Nunez J , Lupon J , Bayes-Genis A
Published: October 2021

Background

Limited data are available on the very long-term trajectory of glomerular filtration rate (GFR) in patients with chronic heart failure (HF).

Purpose

To assess the GFR dynamics estimated by CKD-EPI in a real-life cohort of HF patients over a 14-year follow-up.

Methods

In a prospective observational registry of real-life HF outpatients, estimated GFR (eGFR) was calculated by CKD-EPI at baseline and on a structured schedule every 3 months up to 14 years. We included in the analysis only eGFR values that were assessed at scheduled visits, discarding urgent renal function assessments. Loess (locally weighted error sum of squares) curves were plotted for the whole cohort and subgroups according to vital status up to 14 years of follow-up. Loess curves are useful to observe a trend or relationship on nonlinear data observed over time.

Results

2423 patients were consecutively included from August 2001 to December 2018. Mean age was 67.0±12.7 years, 28,8% were women and 71.1% had HF with reduced ejection fraction (EF<40%). Out of 37360 eGFR values, 25458 were included in the analysis with a median of 8 values per patient [IQR 4–15] and a range between 1 and 47.

Significant changes occurred along the whole trajectory. An initial decline in eGFR was observed during the first three years of follow-up. Subsequently, there was an upward trend during the following five years and after that period a progressive decline was seen until the end of follow-up (Figure 1). In the sub-group of patients who died during follow-up the eGFR slope showed a persistent decline over time of ∼1ml/min/1.73m2 per year. On the contrary, patients who survived to follow-up maintained a stable eGFR (Figure 2).

Conclusions

The eGFR long-term trajectory in patients with chronic HF showed a snaky pattern with an early decrease, mid-term improvement and late progressive decline. Patients who died during follow-up presented a progressive decline from the beginning.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Long-term evolution of eGFRFigure 2. eGFR evolution according to vital status
Derivation of an electronic frailty index for short-term mortality in heart failure: a machine learning approach
Authors: Ju C , Zhou J , Lee S , Tan M S , Liu T , Wu W K K , Jeevaratnam K , Chan E W Y , Wong I C K , Wei L , Zhang Q , Tse G
Published: October 2021

Objective

Frailty may be found in heart failure patients especially in the elderly and is associated with a poor prognosis. However, assessment of frailty status is time-consuming and the electronic frailty indices developed using health records have served as useful surrogates. We hypothesized that an electronic frailty index developed using machine learning can improve short-term mortality prediction in patients with heart failure.

Methods

This was a retrospective observational study included patients admitted to nine public hospitals for heart failure from Hong Kong between 2013 and 2017. Age, sex, variables in the modified frailty index, Deyo's Charlson comorbidity index (≥2), neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) were analyzed. Gradient boosting, which is a supervised sequential ensemble learning algorithm with weak prediction submodels (typically decision trees), was applied to predict mortality. Variables were ranked in the order of importance with a total score of 100 and used to build the predictive models. Comparisons were made with decision tree and multivariate logistic regression.

Results

A total of 8893 patients (median: age 81, Q1-Q3: 71–87 years old) were included, in whom 9% had 30-day mortality and 17% had 90-day mortality. PNI, age and NLR were the most important variables predicting 30-day mortality (importance score: 37.4, 32.1, 20.5, respectively) and 90-day mortality (importance score: 35.3, 36.3, 14.6, respectively). Gradient boosting significantly outperformed decision tree and multivariate logistic regression (area under the curve: 0.90, 0.86 and 0.86 for 30-day mortality; 0.92, 0.89 and 0.86 for 90-day mortality).

Conclusions

The electronic frailty index based on comorbidities, inflammation and nutrition information can readily predict mortality outcomes. Their predictive performances were significantly improved by gradient boosting techniques.

Funding Acknowledgement

Type of funding sources: None.
Prognostic value of sarcopenia and malnutrition in patients admitted for acute decompensated heart failure with reduced or preserved left ventricular ejection fraction
Authors: Ito S , Yamada T , Watanabe T , Morita T , Furukawa Y , Tamaki S , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Kayama K , Kawahira M , Ueda K , Fukunami M
Published: October 2021

Background

Sarcopenia and malnutrition are associated with poor clinical outcome in patients with chronic heart failure. However, there is little information available on the prognostic significance of the combination of sarcopenia and malnutrition in patients with acute decompensated heart failure (ADHF), relating to reduced or preserved left ventricular ejection fraction (HFrEF or HFpEF).

Methods

We prospectively studied 543 consecutive ADHF patients who survived to discharge (HFrEF [LVEF <45%] n=245 and HFpEF [LVEF≥45%] n=298). At the discharge, sarcopenia and malnutrition was evaluated by free-fat mass index (FFMI) and geriatric nutrition risk index (GNRI), respectively. FFMI was calculated as follows: FFMI = (7.38 + 0.02908 × urinary creatinine [mg/day])/ (height in meter)2. Sarcopenia was defined as FFMI <17 kg/m2 in men and <15 kg/m2 in women. GNRI was calculated as follows: 14.89 × serum albumin (g/dl) + 41.7 × BMI/22, and malnutrition was defined as GNRI<92. The endpoint was all-cause death.

Results

During a follow-up period of 2.8±1.4 years, 161 patients had all-cause death. Multivariate Cox analysis showed that both FFMI and GNRI were independently associated with all-cause death in both HFrEF (p=0.0064 and p<0.0001, respectively) and HFpEF patients (p=0.0140 and p=0.0007, respectively) after adjustment for relevant baseline clinical and study characteristics. In HFrEF, patients with both sarcopenia and malnutrition had a significantly higher risk of the total mortality than those with either or none of them. On the other hand, in HFpEF, patients with both and either sarcopenia or malnutrition had a significantly higher risk of the total mortality than those with none of them, while there was no significant difference in the risk between both and either sarcopenia or malnutrition.

Conclusions

Sarcopenia or malnutrition at discharge was associated with all-cause death even in ADHF patients, irrespective of reduced or preserved LVEF. The combination of sarcopenia and malnutrition could provide prognostic information in ADHF patients with reduced LVEF.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Temporal changes in resting heart rate before and after heart failure decompensation in a large real-world population of patients with reduced ejection fraction
Authors: Sarkar S , Koehler J
Published: October 2021

Background

Diagnostic parameters measured in implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy defibrillators (CRTD) have been shown to change before and after heart failure (HF) events with fluid overload.

Purpose

We investigated the temporal characteristics of nighttime heart rate, as a surrogate of resting heart rate, before and after HF events in a large real-world cohort of patients with ICD/CRTD devices.

Methods

We linked a de-identified database of aggregated electronic health record (EHR) data (2007–2017) to a manufacturer's device database with continuous diagnostic monitoring data. Patients with ICD/CRTD implants with HF related diagnostics were included for this study. The device computes nighttime heart rate as the average heart rate between midnight and 4 am. HF event was defined as an inpatient, emergency department, or observation unit stay in a hospital with primary diagnosis of HF and intravenous diuretics administration. Temporal ensemble average of night heart rate in the 60 days pre and post HF events were compared between HF events with and without readmission within 60 days as well as with periods with no HF events.

Results

A total of 17,886 patients with 1.8±1.2 years of follow-up met inclusion criteria. The average age of patients was 66.6±12.3 years, with 72% being males, and 51% with ICD devices. The average night heart rate pre and post HF events with and without readmission and in follow-ups with no events is shown in Figure. A total of 1174 patients had 1425 HF events with no readmission for HF within 60 days and 282 patients had 295 HF events which were followed by readmission for HF within 60 days. A total of 17,839 patients had no HF events over 86,858 follow-up months. A 3-day average night heart rate increased by >3 bpm in a large proportion of patients in the 30-day period before HF event compared to 30-day periods with no events (28% vs 16%; Odds Ratio: 2.08; p<0.001). Patients who were readmitted for HF have higher average NHR before and after admission compared to patients who are not readmitted. In patients who were not readmitted, the night heart rate recovers to baseline levels on an average within 10 days post discharge.

Conclusions

In a large real-world population of patients with ICD/CRTD devices, the average night heart rate increases before HF events. Patients who are readmitted are more likely to have higher night heart rate after discharge.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Medtronic Plc
Discharge FGF23 levels predicts one year outcome in patients admitted with acute heart failure
Authors: Aimo A , Vergaro G , Taurino E , Del Franco A , Fabiani I , Prontera C , Masotti S , Musetti V , Emdin M , Passino C
Published: October 2021

Background

Patients with acute heart failure (AHF) show high levels of fibroblast growth factor-23 (FGF23) on admission. We examined if plasma FGF23 changes during an episode of AHF, and if FGF23 holds prognostic significance in this setting.

Methods

Consecutive AHF patients were enrolled. Blood samples were collected on admission and at discharge. Patients were then followed for all-cause death or HF hospitalization.

Results

Patients (n=125; median age 76 years [interquartile interval 71–83], 63% men, left ventricular ejection fraction 35% [25–56%]) had median admission FGF23 70 ng/L (47–100), N-terminal pro-B-type natriuretic peptide (NT-proBNP) 5,844 ng/L (2,503–10,468), high-sensitivity troponin T (hs-TnT) 40 ng/L (25–72), and soluble suppression of tumorigenesis-2 (sST2) 26 ng/mL (17–37). While other biomarkers decreased, FGF23 increased by 15% from admission to discharge (p=0.033), with a significant correlation with percent changes in estimated glomerular filtration rate (rho=0.306, p=0.001). Over a 12-month follow-up, 64 patients (51%) experienced the endpoint. They were more often men, older, with higher systolic pulmonary artery pressure (sPAP), higher NT-proBNP, hs-TnT and discharge FGF23. The best FGF23 cut-off at discharge from receiver operating characteristics analysis was 78 ng/L. Both discharge FGF23 and the 78 ng/L cut-off independently predicted outcome in models including gender, sPAP, age, and 1) admission NT-proBNP, 2) discharge NT-proBNP, 3) admission NT-proBNP and hs-TnT, 4) discharge NT-proBNP and hs-TnT. The 78 ng/L cut-off also refined risk reclassification.

Conclusions

During an AHF episode, FGF23 increases from admission to discharge, and patients with higher discharge FGF23 have a higher risk of worse outcome.

Funding Acknowledgement

Type of funding sources: None.
Compression wraps as adjuvant therapy in the management of acute systolic heart failure: a pilot clinical trial
Authors: Fadel R , Makki T , Dagher C , Malette K M , Demertzis Z , Ahluwalia G , Sallam O , Miller J , Russell C
Published: October 2021

Background/Introduction

Current guidelines recommend targeting overall decongestion in management of patients with decompensated heart failure. With lower extremity edema among the most prevalent symptoms in patients admitted with decompensation, this often serves as a clinical target. Lower extremity compression wraps (LECW) are seldom used in the acute setting, with little data on efficacy in heart failure, despite serving as a cornerstone of chronic lymphedema management.

Purpose

Evaluate the efficacy of LECW as adjuvant therapy in management of HF with reduced ejection fraction (EF).

Methods

Open-label, randomized, parallel group controlled trial, with 2:1 randomization of adult patients with a history of HF and reduced EF less than 40% admitted to telemetry unit for intravenous (IV) diuretic therapy.

Results

A total of 32 patients were enrolled, with 29 patients completing the study; 19 (66%) in the control arm, and 10 (34%) in the intervention arm. There were no significant differences in baseline characteristics of the two groups. Patients in the intervention arm required less escalation of diuretic therapy (0 vs 5 patients, p=0.079), and less frequent use of continuous infusion therapy (0 vs 7 patients, p=0.027). Total days of IV diuresis was not significantly different between the two groups. Greater net reduction of edema was seen in the intervention group (1.5+ [1–2] vs 1+ [1–2], p=0.072), with fewer cases of acute kidney injury (1 vs 13, p=0.005). The intervention group scored significantly better on MLWHF (55.5 vs 65, p=0.021), including both the physical (17.5 vs 23, p<0.001) and emotional (5.5 vs 11, p<0.001) dimension scores. Overall LOS was shorter in the intervention group (3.5 [3–7] vs 6 [5–10] days, p=0.05). A Poisson regression model was used to examine the effect of intervention on LOS (IRR=0.62, 95% CI 0.44–0.86, p=0.005), suggesting an overall 38% shorter LOS.

Conclusion

In this open-label parallel group RCT, use of LECW resulted in less IV diuretic continuous infusion therapy, greater net reduction in lower extremity edema, reduced patient assessed HF burden, and shorter hospital LOS, with fewer rates of AKI. Trends toward fewer total days of IV diuresis, less escalation of diuresis, and greater reduction in edema were also observed. Larger scale clinical trials are needed to further establish LECW as efficacious adjuvant therapy in the management of acute heart failure.

Funding Acknowledgement

Type of funding sources: None.
Relationship of the degree of coronary lesion and the expression of adipocytokines of local fat depots in patients with coronary artery disease
Authors: Gruzdeva O V , Belik E V , Dyleva Y U A , Sinitsky M Y U , Naumov D Y U , Ivanov S V , Barbarash O L
Published: October 2021

Aims

To reveal the peculiarities of the relationship between of the coronary lesion with the levels of expression of adiponectin, leptin and IL-6 by subcutaneous, epicardial and perivascular adipocytes in patients with coronary artery disease.

Materials and methods

The study included 90 patients with CAD who signed voluntary informed consent. During elective surgery (coronary artery bypass grafting, CABG), samples of subcutaneous adipose tissue (SAT), EAT and PVAT were obtained. Then the patients were divided, depending on the degree of CA, as determined into 3 groups by the SYNTAX Score: moderate (≤22, Group 1), severe (23–31, Group 2), and extremely severe (≥32, Group 3). The expression of adiponectin, leptin and IL-6 was determined by quantitative real-time polymerase chain reaction (qPCR) using TaqManTM Gene Expression Assays (Applied Biosystems, USA) in the ViiA 7 Real-Time PCR System (Applied Biosystems, USA). Statistical analysis was performed using Statistica 9.0.

Results

Evaluation of the studied parameters depending on the degree of coronary lesion according to SYNTAX Score showed that patients with moderate lesion were characterized by the highest level of adiponectin expression in all types of adipose tissue (AT). In severe coronary lesion, an increase in the level of leptin mRNA was observed in the SAT and EAT, and in extremely severe cases, in the PVAT. There was also an increase in the expression of IL-6 in the EAT and PVAT in severe and extremely severe coronary lesions. Using logistic regression analysis it was found that the most significant predictors of severe/extremely severe coronary lesion in CAD are: the expression of adiponectin in the PVAT (odds ratio (OR) 0.44, 95% confidence interval (CI 0.178–0.79, p=0.031) and age (OR=1.4, 95% CI 1.072–1.839, p=0.014) The pathogenetic significance of these markers was confirmed by discriminant analysis, which showed the significance of the expression of adiponectin and IL-6 in the PVAT, leptin in all studied local fat depots to determine the probability of developing severe/extremely severe coronary lesions.

Conclusions

The data obtained indicate a close relationship between the degree of coronary lesion, assessed by the SYNTAX Score, and the expression levels of adipocytokines in local fat depots in patients with CAD. Based on this, it can be concluded that the studied markers are capable of reflecting the degree of coronary artery disease in patients with CAD. The most significant predictors of severe/extremely severe coronary artery disease in CAD is the expression of adiponectin in the PVAT and age.

Funding Acknowledgement

Type of funding sources: None.
Differential microRNAs profile analysis in pericoronary adipose tissue adjacent to atherosclerotic plaque
Authors: Marketou M , Plevritaki A , Kontaraki J , Kalogerakos P , Kochiadakis G , Anastasiou I , Papadaki S , Papadopoulos D , Maragkoudakis S , Parthenakis F , Lazopoulos G
Published: October 2021

Background

Pericoronary adipose tissue (PCAT) regulates arterial homeostasis, is considered to act in paracrine manner, and plays a role in the pathogenesis of atherosclerosis. PCAT may be a source of microRNAs (miRs) that target other tissues and act as messengers for intercellular communication. In this study, we investigated whether the PCATsurrounding coronary occlusive atherosclerotic lesions shows specific miRs expression patterns compared to PCAT surrounding segments without significant atherosclerosis (plaque-free segments). We evaluated expression of miRs that are known to be implicated in the pathophysiology of atherosclerotic disease.

Methods

We included 40 patients (38 men, aged 62±12 years old) with 3-vessel coronary artery disease who underwent elective coronary bypass surgery. The PCAT was harvested from two sites: adjacent to coronary occlusive atheroscleroticlesion and plaque-free segment. miR-133a, miR-21, miR-26b, miR-9 and miR-143 expression levels in PCAT cells were quantified by real-time reverse transcription polymerase chain reaction.

Results

PCAT analysis revealed a significant downregulation of miR-133a levels in periplaque samples compared to those that were not adjacent to atheroscrerotic plaque (35.4±4.3 versus 87.2±130.5, p=0.03). We also found a significant decrease of miR-143 expression in segments adjacent to plaque compared to those surrounding plaque-free coronary artery (72.6±14.3 versus 213.2±222.5, p=0.01). No significant differences between the two sites were observed in PCAT expression of miR-21, miR-26b, miR-9 (170.7±205 versus 130.9±303.2, 129.8±64.3 versus 200.2±330.6, 40±0.2 versus 30.2±3.6, respectively, p=NS for all).

Conclusions

miR-133a and miR-143 expression in PCAT surrounding coronary occlusive atherosclerotic lesions were significantly downregulated compared to PCAT surrounding segments without significant atherosclerosis. Our study opens new perspectives in the role of PCAT in the pathophysiological mechanisms and the treatment of atherosclerotic disease and should be further investigated.

Funding Acknowledgement

Type of funding sources: None.
The quest for GRACE 3.0: improving our beloved risk score with machine learning
Authors: Sousa J , Lima A , Gil P , Henriques J , Goncalves L
Published: October 2021

Background

Although widely recommended for risk assessment of patients with acute coronary syndrome (ACS), the Global Registry of Acute Coronary Events (GRACE) score famously lacks discriminative power. On the other hand, in-hospital serum hemoglobin levels (HG) have been shown to simultaneously forecast both thrombotic and hemorrhagic hazards.

Purpose

To ascertain the extent to which the incorporation of HG in the GRACE score is able to increase its predictive ability.

Methods

Retrospective single-center study encompassing ACS patients consecutively admitted to a Cardiac Intensive Care Unit. Inclusion criteria comprised the acquaintance of GRACE score, HG and vital status on a 6-month follow-up, which served as the outcome. 3 discriminative models were first created: (standard) GRACE score (model 1); GRACE score plus HG, by means of logistic regression (model 2); GRACE score plus HG, by means of multilayer perceptron (a class of feedforward artificial neural network) (model 3). Hereafter, if models 2 and/or 3 were to be found significantly more discriminative than model 1, a correction factor would be calculated, also allowing for the conception of the most predictive model possible (model 4). The discriminative ability was estimated by both the area under the receiver-operating characteristic curve (AUC), and the dyad sensitivity/specificity.

Results

Between April 2009 and December 2016, 1468 patients met study inclusion criteria. Mean age was 68.0±13.2 years and 29.8% were female, while 36.9% presented with ST-segment elevation myocardial infarction. Mean GRACE score was 145.5±47.0 and mean HG was 13.5±2.0. All-cause mortality reached 10.5%, at 6 months. Predictive power for models 1, 2 and 3 may be quantified as follows: AUC 0.6998, sensitivity 77.7% and specificity 62.5%; AUC 0.7818, sensitivity 36.3% and specificity 92.2%; AUC 0.7851, sensitivity 47.7% and specificity 88.5%, respectively. Both models 2 and 3 exhibited more discriminative ability than model 1 (p<0.001), due to their higher specificity. As such, a correction factor was computed (y = −7.8556x + 86.4117) and model 4 was created, displaying a sensitivity of 65.9% and a specificity of 76.5%.

Conclusion

HG single-handedly provides incremental predictive value – namely more specificity – to the GRACE score. In particular, the latter seems to overestimate ACS patients' risk if HG is normal or close to normal.

Funding Acknowledgement

Type of funding sources: None.
Malnutrition affects cholesterol paradox in coronary artery disease: a 41,229 Chinese cohort study
Authors: Wang B , Liu J , Chen S Q , Zhou Z Q , Tan N , Liu Y
Published: October 2021

Background

Several studies found that baseline low LDL-C concentration was associated with poor prognosis in patients with acute coronary syndrome (ACS), which was called “cholesterol paradox”. Low LDL-C concentration may reflect underlying malnutrition, which was strongly associated with increased mortality. We objected to investigate the cholesterol paradox in patients with CAD and the effects of malnutrition.

Method

A total of 41,229 CAD patients admitted to Guangdong Provincial People's Hospital in China were included in this study from January 2007 to December 2018, and divided into two groups (LDL-C <1.8 mmol/L, n=4,863; LDL-C ≥1.8 mmol/L, n=36,366). We used Kaplan-Meier method and Cox regression analyses to assess the association between LDL-C levels and long-term all-cause mortality and the effect of malnutrition.

Result

In this real-world cohort (mean age 62.94 years; 74.94% male), there were 5257 incidents of all-cause death during a median follow-up of 5.20 years [Inter-quartile range (IQR): 3.05–7.78 years]. Kaplan–Meier analysis showed that low LDL-C levels were associated with worse prognosis. After adjusting for baseline confounders (e.g., age, sex and comorbidities, etc.), multivariate Cox regression analysis revealed that low LDL-C level (<1.8mmol/L) was not significantly associated with all-cause mortality (adjusted HR, 1.04; 95% CI, 0.96–1.24). After adjustment of nutritional status, risk of all-cause mortality of patients with low LDL-C level decreased (adjusted HR, 0.90; 95% CI, 0.83–0.98). In the final multivariate Cox model, low LDL-C level was related to better prognosis (adjusted HR, 0.91; 95% CI, 0.84–0.99).

Conclusion

Our results demonstrate that the cholesterol paradox persisted in CAD patients, but disappeared after accounting for the effects of malnutrition.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the National Natural Science Foundation of China (Grant No. 81670339 and Grant No. 81970311), Cardiovascular Research Foundation Project of the Chinese Medical Doctor Association (SCRFCMDA201216)
Temporal trends in the characteristics, treatment and clinical outcomes of conservatively managed patients with non-ST elevation acute coronary syndrome: ACSIS registry 2000–2016
Authors: Aviv Y , Shechter A , Richter I , Kornowski R , Ovdat T , Pereg D , Eisen A
Published: October 2021

Background

Despite advances in percutaneous coronary interventions (PCI), a sub group of acute coronary syndrome (ACS) patients are still managed medically by a conservative approach. We sought to characterize a contemporary, large-scale, real-world cohort of ACS patients treated conservatively via pharmacological management, without PCI.

Methods

Data from the ACS Israeli Survey (ACSIS) accrued between 2000–2016, encompassing all consecutive patients admitted to cardiology wards with an ACS diagnosis. Examined were 3543 conservatively managed patients with non-ST elevation ACS (NSTE-ACS). Patients with ST elevation MI or those referred to bypass surgery were excluded. Primary endpoints were 30-day major adverse cardiovascular events (MACE) and 1-year mortality. The study cohort was divided to 4 time-periods.

Results

Over 2 decades, medically managed NSTE-ACS patients remained of similar age (67±13y, p=0.78), but had more atherosclerotic risk-factors and comorbidities. During time, patients were more often referred to diagnostic angiography and treated with statins, ACE-I/ARBs, and P2Y12 inhibitors (p<0.001 for each). Over time, there were less in-hospital complications such as kidney injury and heart failure. The rate of 30-day MACE decreased (from 20.7% to 10.3%, earliest to latest period, p<0.001). Compared with the earliest period, the latest period was associated with a reduction in 1-year mortality (14.7% to 11.6%; adjusted HR 0.65, 95% CI 0.47–0.90).

Conclusions

Over two decades, in medically managed NSTE-ACS patients, short term prognosis has significantly improved while 1-year mortality demonstrated improvement only recently, likely due to incremental benefits of medical management. Further studies are needed to examine treatment modalities in these unique ACS patients.

Funding Acknowledgement

Type of funding sources: None. Kaplan Meier survival curvesTrends in management and Angiographies
D-dimer as a prognostic factor in patients admitted to a tertiary care intensive coronary care unit
Authors: Turyan Medvedovsky A , Taha L , Farkash R , Bayya F , Dadon Z , Steinmetz Y , Shaheen F , Karameh H , Glikson M , Asher E
Published: October 2021

Introduction

D-dimer is a small protein fragment and is a product of fibrinolysis. A high levels of D-dimer have been suggested as a prognostic factor in cancerous and other critically ill patients. We aimed to evaluate D-dimer levels and outcomes of critically ill patients admitted to a tertiary care intensive coronary care unit (ICCU).

Material and method

All patients admitted to the ICCU at our Medical Center between January 1, 2020 and December 31, 2020 were included in the study. Patients were divided into 2 groups according to their D-dimer level on admission. Low D-dimer level <500 ng/ml, and high D-dimer level ≥500 ng/ml. Survival, in-hospital interventions and complications were compared.

Results and discussion

Overall 1,082 consecutive patients were included, mean age was 67 (±16), 70% were males. Of them 296 (27.4%) had low D-dimer level and 663 (61.3%) had high D-dimer level. Patients with high D-dimer level were older as compared to patients with low D-dimer level (mean age 70.4±15 and 59±13 years respectively, p=0.004), had significantly higher rate of female gender (35.9% vs 15.9% respectively, p<0.0001) and significantly higher rate of any prior cardiac interventions prior to their admission (26.7% vs 4.4% respectively, p<0.0001). Interestingly, patients with high D-dimer level had significantly lower rate of any acute coronary syndrome (ACS) as compared with the low D-dimer group (25.7 vs 66.4% respectively, p<0.0001) and lower rate of smokers (22.5 vs 45.6% respectively, p<0.0001). All 11 post-COVID-19 patients had high D-dimer level on admission.

A multivariate Cox proportional hazards analysis for mortality, adjusted for age, gender, risk factors for cardiovascular disease, ejection fraction<40 found that high D-dimer level was independently associated with higher mortality rates (HR=5.8; 95% CI; 1.7–19.1; p=0.004) as shown in Figure 1.

Conclusion

Elevated D-dimer levels on admission in ICCU patients is a poor prognostic factor of in-hospital morbidity and mortality in the first year following hospitalization.

Funding Acknowledgement

Type of funding sources: None. Cumulative survival according to d-Dimer
A novel index reflecting both anatomical and physiologic parameters in coronary artery disease, the FFR adjusted SYNTAX score (FaSs)
Authors: Park S H , Kang J , Hwang D , Zhang J , Han J K , Yang H M , Park K W , Kang H J , Kim H S , Koo B K
Published: October 2021

Background

Various physiology-based indices have been proposed to predict adverse clinical events in patients with coronary artery disease (CAD), such as the sum of three vessel-fractional flow reserve (3v-FFR), and the functional SYNTAX score (fSS). However, these values could not fully reflect the anatomical factors, which remains as a barrier for clinical application of these indices.

Purpose

To propose a novel index which can reflect both anatomical and physiologic features in CAD patients, and evaluate the additional predictive value for cardiovascular adverse events compared to previous indices.

Methods

For an index which can reflect both anatomical and physiologic features, we proposed the FFR adjusted SYNTAX score (FaSs). The FaSs is calculated by adding the product of the SYNTAX score and `1-FFR', for all three major coronary arteries. Among the 1136 patients who enrolled at 3V FFR-FRIENDS study, we investigated 866 patients, after excluding those who had missing variables. The 3v-FFR, fSS and FaSs were calculated, derived from the baseline FFR and SYNTAX score. Patients were divided into two groups according to the median value of each index. The primary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction and ischemia-driven revascularization) at 2 years follow-up.

Results

Among the total population, MACE occurred in 35 (4.04%) patients. Using the median value in a multivariable COX regression model, only FaSs was associated with an increased risk of MACE, (Hazard Ratio [HR] 5.256, 95% confidence interval [CI] 2.014–13.720), while 3v-FFR (HR 1.383, 95% CI 0.685–2.790) and fSS (HR 1.640, 95% CI 0.830–3.243) were not significantly associated with a higher risk of MACE. This was also observed in the Kaplan Meier survival curve analysis (log-rank p value: p<0.001 for FaSs, 0.153 for 3v-FFR, and 0.061 for fSS; Figure 1) The sensitivity and specificity of the FaSs was 85.7% and 51.6%, which was higher compared to the 3v-FFR (62.9% and 49.3%, respectively) and fSS (57.1% and 58.5%, respectively). When these indices were combined with clinical risk factors (age, sex, hypertension, diabetes, hyperlipidemia, chronic renal failure, LVEF<40%), FaSs was superior compared with 3v-FFR and fSS assessed in regards of the predictive accuracy for MACE (Figure 2).

Conclusion

The FaSs, which is a novel index calculated by a formula using the SYNTAX score and FFR, showed a superior predictive value for MACE compared to previous indices. Our results confirm the importance of considering both anatomical and physiologic parameters in evaluating the patient's risk for cardiovascular adverse outcomes.

Funding Acknowledgement

Type of funding sources: None.
Effect of aspirin treatment duration on clinical outcomes in acute coronary syndrome patients with early aspirin discontinuation and received P2Y12 inhibitor monotherapy
Authors: Chen P.-W , Ho M.-Y , Feng W.-H , Su C.-H , Huang S.-W , Cheng C.-W , Yeh H.-I , Chen C.-P , Huang W.-C , Fang C.-C , Lin H.-W , Lin S.-H , Hsieh I.-C , Li Y.-H
Published: October 2021

Background/Introduction

Recent clinical trials showed that short aspirin duration (1 or 3 months) in dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy reduced the risk of bleeding and did not increase the ischemic risk compared to 12-month DAPT in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). However, it is unclear about the optimal duration of aspirin in P2Y12 inhibitor monotherapy.

Purpose

The purpose of this study was to evaluate the influence of aspirin treatment duration on clinical outcomes in a cohort of ACS patients intolerant to aspirin with early aspirin interruption and received P2Y12 inhibitor monotherapy.

Methods

From January 1, 2014 to December 31, 2018, we included 498 ACS patients with aspirin stopped for various reasons before 6 months after PCI and received P2Y12 inhibitor monotherapy. The efficacy and safety between the groups of early (≤1 month) and late discontinuation (>1 month) of aspirin were compared in 12-month follow up after PCI. To adjust for potential confounding due to baseline imbalances in study covariates while preserving sample size, we used the inverse probability of treatment weights (IPTW) method based on the propensity score.

Results

The mean duration of aspirin treatment was 7.52±8.10 days in the early and 98.05±56.70 days in the late discontinuation group (p<0.001). The primary endpoint was the composite of all-cause mortality, recurrent ACS or unplanned revascularization, and stroke within 12 months. The safety endpoint was major bleeding, defined as BARC 3 or 5 bleeding. In the multivariate Cox proportional-hazards models, there was no difference in the primary endpoint (adjusted hazard ratio 1.19, 95% confidence interval 0.85–1.68) between the groups. The safety outcome of BARC 3 or 5 bleeding was also similar (Figure 1). In conclusion, patients with early discontinuation of aspirin had similar clinical outcomes to those with late discontinuation.

Conclusion

The risk of major adverse cardiac events was similar between those with aspirin treatment >1 month versus ≤1 month in ACS patients undergoing PCI who cannot tolerate aspirin and received P2Y12 inhibitor monotherapy. Under P2Y12 inhibitor therapy, early discontinuation of aspirin ≤1 month after PCI maybe feasible and safe.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): National Cheng-Kung university hospital Figure 1
Prevalence and impact of metabolic syndrome in patients with multivessel coronary artery disease and acute coronary syndrome
Authors: Zhou J , Yan H , Liu C , Zhou P , Li J , Chen R , Zhao X , Wang Y
Published: October 2021

Background

Metabolic syndrome is associated with increased incidence of diabetes and cardiovascular diseases in patients initially free from these diseases. However, its prognostic value in patients with established coronary artery diseases remains controversial.

Purpose

Therefore, we aimed to illustrate the prevalence and investigate the impact of metabolic syndrome in patients with multivessel coronary artery disease and acute coronary syndrome.

Methods

We conducted a large registry of consecutive patients with acute coronary syndrome referred to primary percutaneous coronary intervention and those with multivessel diseases were eligible for this analysis. Metabolic syndrome was defined using modified criteria based on the Adult Treatment Panel III definition from the National Cholesterol Education Program. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction, and stroke.

Results

A total of 2532 patients were included in current analysis and 993 (39.2%) of them had metabolic syndrome while 1539 (60.8%) did not. The prevalence of metabolic syndrome increased over the study period (p for trend = 0.005). There was a significant decline of metabolic syndrome prevalence in patients over 60 years old (p for trend = 0.002) and females had a higher prevalence than their male counterparts (61.5% verse 32.9%, p<0.001). Over a median follow-up of 2.3 years, metabolic syndrome was not significantly associated with MACE (adjusted 95% CI 0.92 to 1.54). In addition, there was no significant difference observed between two groups in other individual outcomes, namely all-cause death, cardiac death, stroke, myocardial infarction, and any revascularization.

Conclusions

Metabolic syndrome was frequently observed in patients with multivessel coronary artery disease and acute coronary syndrome. Patients with metabolic syndrome were more likely to be young and female. However, it was not an independent predictor for MACE after primary percutaneous coronary intervention in those patients.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences Metabolic syndrome distribution in MVDOutcome according to metabolic syndrome