bluuebunny/crossref_metadata_2025 huggingface dataset:
Low levels of dihomo-gamma-linolenic acid are associated with all-cause death in elderly patients with a recent myocardial infarction
Authors: Nilsen D W , Myhre P L , Kalstad A A , Schmidt E B , Arnesen H , Seljeflot I ,   OMEMI investigators
Published: October 2021

Background

In a previous study*, low levels of the omega-6 fatty acid (FA) dihomo-gamma (γ)-linolenic acid (DGLA; C20:3w6), were independently associated with poor 7-year outcome in elderly patients after acute coronary syndrome.

Aim

In order to further evaluate DGLA as a predictor of outcome, we measured n-6 FAs including DGLA in serum samples from elderly subjects with a recent acute myocardial infarction (AMI).

Methods

Baseline samples from the OMEMI (Omega-3 Fatty acids in Elderly with Myocardial Infarction) trial* in which a total of 1027 patients, aged 70 to 82 years, were included 2–8 weeks after an MI, were used. The pre-specified primary outcome during 2 years follow-up was major adverse cardiac events (MACE), which consisted of nonfatal MI, unscheduled coronary revascularization, stroke, all-cause death, or hospitalization for heart failure. Cox regression analysis was used to relate serum n-6 FA levels, measured by gas chromatography and reported as % weight of total FA (%wt) to the risk of incident cardiovascular events. Three models were employed in the multivariable analysis, adjusting for: 1) age, sex and body mass index; 2) + baseline omega-3 FA supplementation; 3) + prevalent hypertension.

Results

Median DGLA levels at baseline (n=1.002) were 2.89 (Q1–Q3 2.43–3.38) %wt. After 2 years follow-up, 152 patients experienced incident MACE, including n=55 all-cause death.

The univariate hazard ratio (HR) for MACE, employing continuous DGLA values was 0.89 (95% CI 0.72–1.08) per %wt increase in DGLA, p=0.24, and for all-cause death 0.72 (95% CI 0.48–1.07), p=0.11. In the multivariable Cox regression models for MACE, concentrations of DGLA did not reach statistical significance; p=0.12, 0.09 and p=0.07 in Models 1, 2 and 3, respectively.

In univariate analysis, HR for total death in the three higher quartiles of DGLA as compared to the lowest quartile was 0.51 (95% CI 0.30–0.80), p=0.016. Results remained statistically significant in all the multivariable models. Model 1: HR 0.54 (0.31–0.95), p=0.03; Model 2: HR 0.50 (0.28–0.91) p=0.02; Model 3: HR 0.49 (0.27–0.88), p=0.017.

Conclusion

Low serum levels of DGLA were associated with increased risk of all-cause death after AMI in elderly patients, thus, suggesting DGLA to be protective.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Stein Erik Hagen Foundation for Clinical Heart Research, Oslo, Norway.
Epicardial adipose tissue volume improves cardiovascular risk reclassification: the Framingham Risk Score example
Authors: Sousa J A , Mendonca M I , Santos M , Temtem M , Mendonca F , Sousa A C , Rodrigues M , Freitas S , Henriques E , Borges S , Guerra G , Drumond A , Palma Dos Reis R ,   GENEMACOR study
Published: October 2021

Introduction

Epicardial adipose tissue (EAT) volume can be noninvasively detected by CT and has been suggested to predict major adverse cardiovascular events (MACE). Framingham Risk Score is one of a number of scoring systems used to determine an individual's chances of developing cardiovascular disease, hence identifying who is most likely to benefit from prevention.

Objectives

The purpose of this study was to determine net reclassification improvement (NRI) and improved risk prediction based on EAT volume, in comparison to a traditionally known cardiovascular risk score, such as the Framingham.

Methods

895 asymptomatic volunteers were prospectively enrolled in a single Portuguese center (mean age 51.9±7.7, 78.5% male) and underwent a median follow-up time of 3.7 years (IQR 5.0). EAT volume was measured by Cardiac Computed Tomography (CCT) using a modified simplified method. For NRI assessment, EAT volume as a continuous variable was added to the Framingham Risk Score.

Results

After 3.7 median years of follow-up, 27 patients developed a MACE. Using NRI, the net proportion of events (netNRIe) that assigned a higher risk was 33.3% (better reclassified), and the net ratio of non-events (netNRIne) was 24.7%, resulting in a net reclassification index (netNRI) of 58.0%. When the new marker was included in the model, 58.0% of patients were better reclassified. In our work, a total of 33.3% of patients who suffered events (n=27) were correctly reclassified and assigned a higher risk.

Conclusion

EAT volume results in a high reclassification rate in an asymptomatic, low-risk population, demonstrating the benefit of this marker beyond traditional risk assessment models. Our study supports its application, especially in carefully selected individuals.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Role of statins in patients with MINOCA. A systematic review and meta-analysis
Authors: Lobo L M , Masson W , Molinero G , Levalle Cobo A , Benincasa F , Wehit G , Delgado J , Losada P , Suarez F , Barbagelata L
Published: October 2021

Background

Given the complex etiology and a limited amount of evidence, the medical treatment (including statin use) of myocardial infarction with non-obstructive coronary artery disease (MINOCA) remains uncertain. The objective of the present study was to evaluate the effect of statin therapy on major cardiovascular events (MACE) and mortality in MINOCA patients.

Methods

A systematic review and meta-analysis of time-to-event outcomes were performed from statin's studies therapy on MINOCA patients, reporting data from MACE or mortality, after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases.

The Meta-analysis Of Observational Studies (MOOSE) and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were used to check the reporting of observational studies. The quality of the included studies was assessed by two independent review authors using the Newcastle-Ottawa Scale (NOS). The summary effect of statin therapy on the endpoints were calculated. Measures of effect size were expressed as HRs, and the I2 statistic was calculated to quantify between-studies heterogeneity and inconsistency. A fixed-effects meta-analysis model and sensitivity analysis was then applied. The level of statistical significance was set at a 2-tailed alpha of 0.05.

Results

Six observational studies of statin therapy on MINOCA, involving a total of 11171 patients, were identified and considered eligible for analysis (9129 subjects received statin therapy while 2042 patients were part of the respective control arms). Quantitative analysis (5 studies were included) showed that statin use was associated with lower mortality (HR: 0.65; 95% CI: 0.56–0.75, I2: 0%). Also, the meta-analysis showed that statin therapy was associated with a lower incidence of MACE (HR: 0.78; 95% CI: 0.69–0.88, I2: 27%).

Conclusion

Our data suggest that in a population with MINOCA, the use of statin therapy results in significant reduction on MACE and mortality. These results must be confirmed in future clinical trials.

Funding Acknowledgement

Type of funding sources: None. Mortality and MACESensitivity analysis
Traditional risk factor control in the Russian cohort of the hospital arm of EUROASPIRE V survey as compared to the whole study population
Authors: Pogosova N , Boytsov S A , Ausheva A K , Sokolova O Y , Salbieva A O , Karpova A V , Yusubova A I , Pozdnyakov Y M
Published: October 2021

Background

Regular monitoring of risk factors control in patients (pts) with atherosclerotic cardiovascular diseases is of paramount importance for interventions and policies targeting secondary prevention settings.

Purpose

To describe traditional risk factors control in men and women with history of acute coronary syndromes (ACS) or cardiac revascularization enrolled into the hospital care arm of EUROASPIRE V (European Action on Secondary and Primary Prevention by Intervention to Reduce Events) study in Russian centers vs the whole study population.

Methods

The hospital arm of EUROASPIRE V was a cross sectional survey covering multiple European countries including Russia. Within each country one or more hospitals were selected where consecutive pts (both genders, ≥18 and <80 years of age) hospitalized for myocardial revascularization procedures or for ACS were retrospectively identified. Identified patients were invited for interview, which had to take place ≥6 months and <2 years after the index hospitalization. The risk factors control was assessed during the interview.

Results

A total of 399 pts (women, 27.1%) have been interviewed in Russia vs 8261 pts (women, 25.8%) in the whole survey. The mean age of the Russian cohort at interview was 62.8±8.7 years in Russia vs 63.6±9.6 years in all EUROASPIRE V pts. The proportion of pts with uncontrolled risk factors in Russia vs the whole survey population was as follows: current smokers 19.0% vs 18.7%, obesity 47.0% vs 37.7%, abdominal obesity 60.4% vs 58.5%, uncontrolled diabetes 52.9% vs 45.6%, blood pressure (BP) not at goal 36.0% vs 46.3% and uncontrolled LDL cholesterol in 72.4% vs 71.0%, respectively. The table below represents uncontrolled risk factors by gender in Russian pts and in the whole study population.

Conclusion

Both in Russian centers and in the whole survey participants there was a considerable room for improvement o risk factors control. Smoking seemed to be a more common issue in men whereas obesity, uncontrolled diabetes and low physical activity were more prevalent in women.

Funding Acknowledgement

Type of funding sources: None. Table 1
Novel insights into the management of German patients with very high cardiovascular risk eligible for PCSK9 inhibitor treatment: baseline characteristics from the PERI-DYS study
Authors: Laufs U , Birkenfeld A L , Fraass U , Hohenstein B , Siegert C , Klotsche J , Parhofer K G , Pittrow D , Dexl S , Salmen S , Schettler V J J , Steinhagen-Thiessen E ,   PERI-DYS Study Group
Published: October 2021

Background

The reasons why patients are treated or not with PCSK9 inhibitors (PCSK9i) are incompletely understood. In Germany, access to PCSK9i is limited by local regulations and many high-risk cardiovascular patients do not receive these therapies. The PERI-DYS study aims to describe and compare two groups of dyslipidaemia patients at very high CV risk: those treated with PCSK9i compared with patients qualifying for but not treated with PCSK9i.

Methods

Observational study with up to 2000 consented patients, documented mainly by office-based cardiologists or physicians in lipid ambulances with data extracted from patient charts. Lipid lowering treatment (LLT) at enrolment includes ongoing PCSK9i use, newly initiated PCSK9i, statins, ezetimibe, and lipoprotein apheresis. Patients are followed for up to 3 years, with visits every 6±2 months to record LLT (drugs, dosing), other CV medications, lipid and glucose values, blood pressure, clinical events (major adverse cardiac and cerebrovascular events) and adverse drug reactions.

Results

As of 05 March 2021, 1488 patients have been enrolled across 70 sites. The majority of patients (91.5%) had heterozygous familial or non-familial hypercholesterolemia or mixed dyslipidaemia. At enrolment, 49.4% of patients were receiving PCSK9i (35.4% ongoing and 14.0% newly treated). Among PCSK9i users, the majority were receiving evolocumab 140 mg (n=567, 38.1% of all enrolled patients). There were no major differences in demographics and non-lipid lowering medication, with the exception of more females in the PCSK9i group.

The estimated untreated LDL-C based on “back-calculation” was higher in patients who were on ongoing PCSK9i therapy than in those not on PCSK9i or newly treated with PCSK9i (Table 1). Physician-reported statin intolerance was much more common in the two PCSK9i groups compared with the non-PCSK9i group (67% versus 14%). Patients in the PCSK9i groups received fewer concomitant statins. Mean on-treatment total cholesterol and LDL-C were considerably lower in patients who were on ongoing PCSK9i compared to non-PCSK9i. Overall, nicotinic acid, fibrates, cholestagel, and omega-3 fatty acids were rarely used (data not shown).

Conclusions

Patients treated with PCSK9i and those qualifying for but not treated with PCSK9i had similar baseline characteristics, but the former had higher estimated untreated LDL-C values and a higher rate of statin intolerance. Ongoing follow-up will determine the prognostic importance of these findings.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Amgen GmbH Germany
Increased lipoprotein(a) multiplies coronary heart disease risk in patients with familial hypercholesterolemia
Authors: Barkas F , Anastasiou G , Adamidis P , Koutsogianni A D , Rizos C , Liamis G , Elisaf M , Liberopoulos E
Published: October 2021

Background

Familial hypercholesterolemia (FH) and elevated lipoprotein(a) (Lp[a]) are individually associated with increased coronary heart disease (CHD) risk.

Purpose

To determine the independent and joint associations of FH and Lp(a) with CHD.

Methods

This was a cross-sectional study including adult patients with dyslipidemia followed at our University General Hospital, Greece. FH diagnosis was based on the Dutch Clinic Lipid Network Criteria (score ≥5), while elevated Lp(a) levels were defined as >30 mg/dL. Independent and joint associations of FH and Lp(a) with CHD prevalence were determined using binary logistic regression models adjusted for traditional cardiovascular risk factors.

Results

Among 941 participants (49 years, 47% males, 54% with FH, 36% with increased Lp[a]), the prevalence of CHD was 7.7% (n=72). Compared with subjects without FH and non-elevated Lp(a) (n=296), those with either FH (adjusted OR: 3.21, 95% CI: 1.35–7.62, n=271) or elevated Lp(a) (adjusted OR: 1.89, 95% CI: 0.76–4.69, n=180) were at higher CHD risk. The patients with both FH and elevated Lp(a) had the highest CHD risk (adjusted OR: 7.31; 95% CI: 3.09–17.32, n=195). Among FH patients, increased Lp(a) doubled CHD risk (adjusted OR: 2.22, 95% CI: 1.02–4.83), whereas among patients with elevated Lp(a), FH was associated with a 5-fold increase in CHD risk (adjusted OR: 4.96, 95% CI: 1.83–13.43).

Conclusions

FH and elevated Lp(a) have independent and additive associations with CHD prevalence. This may have therapeutic implications regarding treatment intensity.

Funding Acknowledgement

Type of funding sources: None.
Incomplete functional reverse remodelling of the left ventricle one year after bariatric surgery. Insights from the prospective FatWest study
Authors: Grymyr L M D , Nadirpour S , Gerdts E , Nedreboe B G , Hjertaas J J , Matre K , Cramariuc D
Published: October 2021

Background

Patients with severe obesity are predisposed to development of left ventricular (LV) hypertrophy with subsequent increased myocardial oxygen demand and impaired myocardial function. Bariatric surgery leads to rapid weight loss and improves cardiovascular risk profile.

Purpose

To assess whether LV systolic function, wall mechanics, and cardiac power improve 1 year after bariatric surgery.

Methods

91 severely obese patients (43±10 years, 70% women, body mass index [BMI] 41.7±4.9 kg/m2, 55% with hypertension, 17% with diabetes mellitus) underwent echocardiography before, 6 and 14 months after Roux-en-Y gastric bypass surgery in the prospective FatWest (Bariatric Surgery on the West Coast of Norway) study. We assessed LV systolic function by biplane ejection fraction (EF), LV wall mechanics by midwall shortening (MWS) and global longitudinal strain (GLS), and cardiac power normalized for LV mass by 0.222 x cardiac output x mean blood pressure (BP)/LV mass.

Results

Surgery induced a significant reduction in BMI, heart rate, systolic BP, and LV mass (Figure 1). Prevalence of LV hypertrophy fell from 34 to 20% 14 months after surgery (p<0.001), while that of concentric geometry remained stable: 8 vs 10% (p=0.36). GLS improved by 28%, however LV EF and MWS did not change (Figure 2). LV power at rest decreased postoperatively, reflecting the lower BP and heart rate, but was unaltered when normalized for LV mass (Figure 2). In backward stepwise multivariate regression analyses, 1 year improvement in GLS was predicted by the systolic BP reduction (p<0.05) (R2 0.73, p<0.001), while low 1-year MWS was independently associated with female gender, concentric geometry and higher myocardial oxygen demand (all p<0.01) (Nagelkerke R2 0.44, p<0.001), and lower 1-year LV power-mass with female gender and LV hypertrophy (p<0.01) (R2 0.24, p<0.001).

Conclusion

In severely obese patients, LV longitudinal function normalizes 1 year after bariatric surgery, mainly due to the BP reduction. LV midwall mechanics and power do not improve, especially in women and patients with persistent LV geometric abnormalities.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
HF and CKD present a dire prognosis in young Type 2 Diabetic patients
Authors: Seabra Carvalho D , Gavina C , Valente F , Bernardo F , Santos Araujo C , Taveira Gomes T
Published: October 2021

Introduction

Type-2 diabetes (T2D) is one of the most relevant risk factors for both heart failure (HF) and chronic kidney disease (CKD). Target organ damage causes significant morbi-mortality, especially when these two conditions are combined with diabetes.

Understanding the natural history of the combination of these conditions is paramount to implement tailored preventive measures.

Purpose

To estimate the risk of all-cause death, cardiovascular (CV) death and non-fatal major CV events (MACE) in T2D patients younger than 65 years, either: i) without HF or CKD, ii) with HF (T2D-HF), or iii) with CKD (T2D-CKD) in a real-world clinical setting.

Methods

Retrospective cohort study performed in a healthcare centre that provides primary and secondary care. It included adults with T2D aged between 40 and 65 years of age stratified into three groups: i) T2D with HF defined as either: Ejection Fraction (EF) ≤40% and NT-proBNP ≥200pg/mL (≥600pg/mL if atrial fibrillation (AF)) or BNP ≥100pg/mL (≥125pg/mL if AF); EF >40% in the presence of structural cardiac abnormalities), ii) T2D with CKD (eGFR ≤60mL/min using EPI-CKD formula) and T2D without HF or CKD. We modelled 1-year risk for CV death, all-cause mortality and non-fatal MACE using multivariate weighted cox regression models clustered by patient. Models were adjusted for age (using penalized splines), sex, age-sex interaction, prior history of hypertension, myocardial infarction, stroke, and peripheral arterial disease. We reported hazard ratios (versus T2D without HF or CKD) with 95% confidence intervals.

Results

We identified 14986 patients with T2D without HF or CKD, 1101 with T2D with HF and 3114 with T2D with CKD. Patients were in general 55–58 years old, with a slight predominance of the male gender across the groups. Event rate was 14% in T2D with HF, 15% in T2D with CKD and 5% in TD2 without these conditions.

One-year all-cause death risk was 2.77 (2.26–3.40) for T2D-HF and 3.09 (2.77–3.45) for T2D-CKD. CV death risk was 2.59 (1.72–3.91) for T2D-HF and 2.75 (2.19–3.46) for T2D-CKD. Non-fatal MACE risk was 2.82 (2.34–3.41) for T2D-HF and 1.90 (1.66–2.17) for T2D-CKD. Regarding MACE, the event rate was 32% in T2D-HF, 13% in T2D-CKD but only 6% in T2D. T2D-HF was associated with the highest risks of myocardial infarction (3.25 [2.60–4.06]) and end-stage kidney disease (9.9 [7.3–13.43]) when compared to T2D-CKD.

Conclusions

Young patients with T2D combined with HF or CKD have an increased risk of early adverse CV and renal events. HF was linked with highest risk of myocardial infarction and end-stage kidney disease.

These findings highlight the importance of an early identification and management of HF and CKD in T2D patients.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): AstraZeneca Produtos Farmacêuticos Lda Figure 1. Outcomes for HF and CKD groups
Fibroblast growth factor 21 and adipose tissue distribution in young adult with abdominal obesity
Authors: Zheleznova E , Zhernakova Y U , Blinova N , Azimova M , Shariya M , Sharf T , Masenko V , Chazova I
Published: October 2021

Introduction

Fibroblast growth factor 21 (FGF-21) is a hormone-like protein that is involved in the regulation of glucose and lipid homeostasis. Several studies have reported the association of FGF21 with visceral fat, epicardial fat, and pericardial fat. However, there is limited information about distribution of FGF21 levels in young adults with different metabolic status and its relationship to different body fat.

Objective

The main aim of study was to investigate the association between subcutaneous (SF), visceral (VF), periaortic (PF), epicardial (EF), perirenal (PRF), renal sinus (RSF) fat and fibroblast growth factor 21 (FGF21) in young adult with abdominal obesity (AO), or with metabolic syndrome (MS).

Purpose

To assess the level of FGF21 in blood serum in young people with AO and compare it with the distribution of adipose tissue.

Methods

There were 132 adult 18–45 y.o. in the study. We formed 3 groups: health (n=16, M - 43,8%, av.age 32 [27; 35]); AO plus 1 or less sing of MS (AO) (n=46, men (M) – 37,0%, av.age 40 [34; 43]), and MS (n=70, M – 81,4%, av.age 40 [35; 44]). Height, weight, BMI, waist circumference, blood tests (fast glucose (FG) and glucose tolerance (GT), lipid profile, insulin, adiponectin (ELISA, Mediagnost), leptin (ELISA, DBC), FGF21 (ELISA KIT, BCM Diagnostics) were measured. MS was defined as AO (cut-off of >80cm in women (W) and >94cm in M) plus >1 sign: HDL<1,30(w)/1,04(m)mmol/l; triglycerides>1,7mmol/l; FG>5,6mmol/l; violation GT; BP>140/90mmHg. SF, VF, PF, EF, PRF, RSF (range: −150 to −30 HU) was measured by computed tomography. We calculated ratio subcutaneous to visceral fat (RSV). 24-hour blood pressure monitoring was performed.

Results

The clinical characteristics of the groups are presented in table 1. We didn't find any difference of level FGF 21 between groups AO (294,4 pg / ml [110,0; 583,5]) and MS (245,7 pg/ml [129,2; 474,8]). But in health group (110,2 pg/ml [62,2; 221,9] it was significant lower (p=0,05). We found significant week relationship FGF 21 with VF (r=0,02, p<0,05) and SF (r=0,02, p<0,05), and insignificant association with PF (r=0,11 p>0,05), EF (r=0,04 p>0,05), PRF (r=−0,17 p>0,05), RSF (r=−0,02 p>0,05). Also, we checked association with other parameters (insulin (r=0,15 p>0,05), adiponectin (r=0,00 p>0,05), glucose (r=0,12 p>0,05)) and found a statistically significant association FGF21 with leptin (r=0,24, p<0,01).

Conclusions

Young adults with abdominal obesity had elevated level of FGF21. And it was associated with visceral, subcutaneous fat depots and leptin.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of Russian Federation Table 1. Clinical characteristics of the groups
Prognostic value of the hemodynamic gain index in different groups of patients undergoing cardiopulmonary exercise stress testing
Authors: Chaikijurajai T , Wu Y , Grodin J L , Harb S , Jaber W , Tang W H W
Published: October 2021

Background

A novel hemodynamic parameter obtained from the cardiopulmonary exercise testing (CPET), the hemodynamic gain index (HGI), was developed and shown to be a strong independent predictor of all-cause mortality in a large male cohort. The HGI also strongly correlates with exercise parameters such as peak oxygen consumption and metabolic equivalents (METs). However, prognostic implications of the HGI have not been externally validated with subgroup analyses based on sex, heart failure (HF), coronary artery disease (CAD) and the use of beta-blockers.

Purpose

We aimed to validate the prognostic value of the HGI in men, women, and patients with and without HF, CAD, and beta-blocker use.

Methods

We identified 126,356 consecutive patients undergoing treadmill exercise testing for symptom evaluation between 1/1/1991–02/27/2015. HGI was calculated using the formula, [(SBPpeak x HRpeak) − (SBPrest x HRrest)] / (SBPrest x HRrest). Univariable and multivariable cox regression models were used to determine the associations between the HGI stratified by quartiles and all-cause mortality at 10 years with adjustment for cardiovascular risk factors (age, sex, diabetes, hypertension, dyslipidemia, chronic kidney disease, smoking status and body mass index) and exercise testing parameters (chronotropic reserve index, METs, abnormal heart rate recovery, and total exercise time).

Results

In our study cohort, mean age was 53.5±12.6 years. There were 74,724 (59.1%) male, 5,940 (4.7%) HF, 21,123 (16.7%) CAD, and 30,568 (24.2%) beta-blocker-using patients. During the mean follow up of 8.7 years, 9,929 (7.9%) died. Mean HGI was 2.0±1.2 bpm/mmHg. Lower HGI was associated with all-cause mortality in the entire cohort (Figure 1A, log rank p<0.001). After adjustment for the covariates, the lowest quartile of the HGI was independently associated with all-cause mortality in subgroups of men, women, and patients with and without HF, CAD, and beta-blocker use (Figure 1B, all p≤0.001) compared with the highest quartile of the HGI.

Conclusions

HGI is an independent predictor of long-term mortality after adjusted for traditional cardiovascular risk factors, and exercise performance across patient subgroups.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Kaplan-Meier curve and Cox regression
Characteristics of warfarin underprescription in older adults with atrial fibrillation
Authors: Rashid S , Tysarowski M , Naranjo J , Dhole A , Petrovic L , Aziz E F
Published: October 2021

Objectives

The prevalence of atrial fibrillation (AF) and atrial flutter (AFl) increases with age. Prior research suggests that underprescription of anticoagulants, such as warfarin, in older adults can lead to increased morbidity and mortality. We analyzed rates and patterns of warfarin prescription in older adults.

Methods

In this prospective observational study, we enrolled 2179 consecutive patients with admission diagnosis of AF or AFl. Those placed on a non-warfarin anticoagulation (189 patients) were excluded. Patients were then divided into “older cohort” (≥75 years of age) and “younger cohort” (<75 years of age). Within the older cohort, prescription patterns of warfarin were analyzed. Serial prospective follow-up was 3.1±2.06 years.

Results

Of the 1990 patients, 46.9% were ≥75 years older, of which 51.1% were prescribed warfarin. There was no difference between mean CHA2DS2-VASc score and warfarin prescription (OR=1.06 (95% CI 0.93–1.21), p=0.388) in the older cohort. After adjusting for hypertension, glomerular filtration rate, and Black race, appropriate warfarin prescription in older adults was independently associated with lower aspirin prescription rates (OR=0.57 (95% CI 0.43–0.75), p<0.001), lower body mass index (OR=1.03 (95% CI 1.01–10.6), p=0.018), and lower hemoglobin levels (OR=1.11 (95% CI 1.04–1.19), p=0.002).

Conclusions

In our study, adults 75 years and older with AF and AFl tended to have lower rates of warfarin prescription despite higher CHA2DS2-VASc score and higher risk of thromboembolic events. Anemia, lower weight, and aspirin use were characteristics associated with warfarin underprescription. These patterns can shed light on clinicians' perceived hesitancy to anticoagulate certain older adults.

Funding Acknowledgement

Type of funding sources: None.
Right ventricle strain changes in patients with breast cancer during anthracycline therapy
Authors: Laufer-Perl M , Gvili M , Sirota Dorfman S , Baruch G , Rothschild E , Beer G , Arbel Y , Rozenbaum Z , Topilsky Y , Kapusta L
Published: October 2021

Background

Cardiotoxicity has become a significant adverse effect of cancer therapy, with Anthracyclines (ANT) in particular. There is a crucial need for the early subclinical detection of cardiotoxic effect. We aimed to evaluate Right ventricle (RV) two-dimensional speckle tracking echocardiography (2D-STE) changes during ANT therapy and to assess the correlation between RV 2D-STE and the routine echocardiographic RV parameters.

Methods

Data were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). All female patients with breast cancer, planned for ANT therapy were included. All patients underwent serial echocardiography exams including baseline RV 2D-STE (before chemotherapy, T1) and shortly after the completion of ANT therapy (T3). RV 2D-STE was evaluated using the apical 4 chamber (4C) RV-focused view, assessing both the combined RV free wall and inter-ventricular septum (RV GLS) and solely the RV free wall strain (RV FWLS). Significant reduction in both RV GLS and RV FWLS was determined by either a relative reduction of >10% or an absolute value of >−25% for RV GLS and >−29% for RV FWLS.

Results

From September 2016 to June 2019, 40 patients were evaluated with a mean Doxorubicin (type of ANT) dose of 238.5±9.4 mg/m2. RV FWLS showed significant correlation to Tricuspid annular plane systolic excursion. At T3, significant reduction in both RV GLS and RV FWLS was observed among 77% and 62% of the patients with a mean RV GLS and RV FWLS reduction from −26.8 (±4.7) % to −21.5 (±4.4) % and −28.9 (±5.1) % to −25.6 (±5.9) % (p<0.001, p=0.002), respectively. Left ventricle (LV) ejection fraction and LV GLS were within the normal range.

Conclusions

RV GLS and RV FWLS reduction are frequent and occur early in the course of ANT therapy, preceding LV dysfunction, which may imply for the role of RV 2D-STE in the detection of early cardiotoxicity.

Funding Acknowledgement

Type of funding sources: None.
The effects of dapagliflozin on kidney and cardiovascular outcomes in patients with chronic kidney disease with and without heart failure
Authors: Heerspink J L , Wheeler D C , Vart P , Jongs N , Hou F F , Langkilde A M , Correa-Rotter R , Rossing P , Sjostrom C D , Toto R D , Chertow G M , Stefansson B V , McMurray J J V ,   DAPA-CKD
Published: October 2021

Background

Heart failure (HF) is highly prevalent in patients with chronic kidney disease (CKD) and the severity of kidney impairment increases risk of HF, highlighting the deleterious interplay between the conditions. The DAPA-CKD trial showed that dapagliflozin reduced the risk of kidney failure and HF hospitalization in patients with CKD.

Purpose

This prespecified analysis of DAPA-CKD aimed to determine the effects of dapagliflozin on kidney, cardiovascular and mortality outcomes according to presence or absence of HF.

Methods

DAPA-CKD (NCT03036150) was a randomized, double blind, controlled trial, which enrolled 4,304 participants with CKD. Participants were randomized to dapagliflozin 10 mg/day or placebo, as adjunct to standard care, and were followed for a median 2.4 years. The primary endpoint was a composite of sustained decline in eGFR ≥50%, end-stage kidney disease, or renal or cardiovascular death. Key secondary endpoints included a composite of cardiovascular death or HF hospitalization and all-cause mortality.

Results

Overall, 468 (11%) participants had a HF diagnosis at baseline. Participants with HF were older (65.3 vs 61.4 years) and more frequently diagnosed with type 2 diabetes (77% vs 66%) compared with those without HF; mean eGFR was similar (43.2 vs 43.1 mL/min/1.73m2) in the two groups. The primary outcome occurred more frequently in those with versus without HF (8.8 vs 5.7 events per 100 patient-years, respectively). The effect of dapagliflozin on the primary outcome was consistent among those with (hazard ratio [HR] 0.58; 95% CI 0.37, 0.91) or without HF (HR 0.62; 95% CI 0.51, 0.75; p-interaction 0.59). The composite of cardiovascular death or HF hospitalization (HR 0.68; 95% CI 0.44, 1.05 vs 0.70; 95% CI 0.51, 0.97; p-interaction 0.90), and the relative risk reduction for mortality (HR 0.56; 95% CI 0.34, 0.93; vs 0.73; 95% CI 0.54, 0.97; p-interaction 0.39) were also consistent in those with or without HF.

Conclusion

Patients with co-existing CKD and HF are at high risk of kidney and cardiovascular events and premature mortality. Dapagliflozin consistently reduced the proportional risk of these events, regardless of the presence or absence of HF.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): AstraZeneca
Telmisartan for treatment of Covid-19 patients: an open randomized clinical trial
Authors: Duarte M , Pelorosso F , Nicolosi L N , Salgado V , Vetulli H M , Arquieri A , Azzato F , Coyle J , Davolos I , Fernandez Criado I , Gregori R , Rubio M C , Sarquis S M , Whalmann F , Rothlin R P
Published: October 2021

Background

The imbalance of the Renin Angiotensin System in favor of the angiotensin II has been described in Covid-19-patients. Angiotensin II regulates life processes, such as cell growth and division and can promote apoptosis initiating an inflammatory process with release of proinflammatory cytokines. Angiotensin receptor blockers (ARBs) block the AT1 receptor and could have a beneficial effect reducing Covid-19 inflammation.

Purpose

To assess whether Telmisartan is effective in reducing C-reactive protein (CRP) plasma levels in hospitalized patients with Covid-19, and improves clinical outcomes and length of stay and morbimortality.

Trial design

This is a parallel-group, randomized, two-arm, open-label, multicenter superiority trial with 1:1 allocation ratio.

Methods

Inclusion criteria: patients aged more than 18 years with less than 5 days of symptoms onset and after informed consent was obtained.

Exclusion criteria: Patients admitted to intensive care unit (ICU) or using mechanical ventilatory support or ongoing ARBs / angiotensin-converting enzyme inhibitors treatment at the time of randomization. Control arm received standard care alone and treatment arm Telmisartan 80 mg bid 14 days added to standard care. Primary outcome were CRP plasma levels at day 5 and 8 after randomization. Secondary outcomes included time to discharge at 15 days, admission to ICU and death at 15 and 30 days.

Results

158 patients were included in the analysis, 80 in the control and 78 in the telmisartan group. Day 5 control-group CRP levels were 6.06±6.95 mg/dL (n=66) while telmisartan group were 3.83±5.08 mg/dL (mean±SD; n=66, p<0.05). Day 8 CRP levels were 6.30±8.19 mg/dL (n=44) and 2.37±3.47 mg/dl (mean±SD; n=43, p<0.05) in the control and telmisartan groups, respectively. Kaplan-Meier analysis showed that Telmisartan-treated patients had lower median time to discharge (control=15 days; telmisartan=9 days). Death by day 30 was reduced by 81% in the telmisartan-treated group (control 22.54%, 16/71; telmisartan 4.29%, 3/70 participants; p=0.0023). Composite ICU, mechanical ventilation or death was reduced by telmisartan treatment at days 15 and 30. No telmisartan-related adverse events were reported.

Conclusions

Telmisartan, an inexpensive safe drug, in high doses, demonstrated anti-inflammatory effects and reduced morbimortality in Covid-19-hospitalized patients.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s):Hospital Escuela José de San Martín, ArgentinaHospital Español de Buenos Aires, Argentina Probability of discharge up to
Prognostic impact of treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the acute phase and medium-term on COVID-19 infected patients
Authors: Broco-Fernandez C , Varela-Lopez A , Diaz-Argueso L , Cacho-Antonio C E , Antunez-Muinos P J , Otero-Garcia O , Jimenez-Ramons V , Gonzalez-Ferreiro T , Perez-Poza M , Bastos-Fernandez M , Garcia-Campos A , Lopez-Pais J , Lopez-Otero D , Gonzalez-Juanatey J R ,   CARDIOVID
Published: October 2021

Introduction

The first case of COVID-19 infection was described in Wuhan, China, in December 20191. Shortly after, cases of limited human-to-human transmission were reported in other countries, which made the WHO declare the outbreak a Public Health Emergency of International Concern (ESPII) on January 30, 20202.

Recent studies suggest that treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARAB) during acute COVID-19 infection has no effect on mortality3, but it is no evidence regarding the medium-term clinical implication of previous treatment with ACEI/ARAB on the prognosis of patients with COVID-19 infection.

Purpose

The aim of this study is to evaluate the clinical implication of the use of ACEI/ARB in the acute moment and in medium-term follow-up in patients after COVID-19.

Methods

It is a single-centre, retrospective, analytical observational study of cohorts based on all consecutive patients diagnosed with COVID-19 who were admitted during the first wave (March 10th until May 31st), of the pandemic in our health area. Survival analysis of main outcomes (mortality, heart failure, and major acute cardiovascular events [a composite of cardiovascular mortality, myocardial infarction and stroke]) were adjusted by multivariate logistic regression.

Results

Of the total population studied, 447,979 inhabitants, 1,030 (0.23%) were diagnosed with COVID-19 infection, of which 196 (19%) were under treatment with ACEI/ARB at the time of diagnosis. The main results showed that ACEI/ARB treatment (combined and individually) had no effect on mortality (Hazard Ratio [HR]: 1.64, 95% Confidence Interval [CI] 0.98 2.76, p=0.062), heart failure (HR: 0.98, 95% CI 0.53 1.79, p=0.942), thrombotic events (HR: 1.02, 95% CI 0.22 4.83, p=0.98) and major acute cardiovascular events (HR: 0.88, 95% CI 0.48 1.60, p=0.665).

Conclusions

In conclusion, previous treatment with ACEI/ARB in patients with COVID-19 had no effect on the 6-month prognosis, defined as mortality, heart failure, or major acute cardiovascular events.

Withdrawal of ACEI/ARB in patients testing positive for COVID-19 would not be justified, in line with current recommendations of scientific societies and government agencies.

Funding Acknowledgement

Type of funding sources: None.
Effectiveness and safety of oral anticoagulants in the treatment of acute venous thromboembolism: a comparative cohort study in France
Authors: Bertoletti L , Gusto G , Khachatryan A , Quignot N , Chaves J , Moniot A , Mokgokong R
Published: October 2021

Background

RCT evidence has shown that direct oral anti-coagulants (DOACs) are at least as effective and safer in terms of bleeding, compared to vitamin K antagonists (VKAs) in the treatment of acute venous thromboembolism (VTE).

Purpose

To compare the risks of recurrent VTE and of bleeding leading to hospitalisation, in patients treated with DOACs (each compared with VKAs) for acute VTE in a real-world setting.

Methods

A retrospective cohort study of treatment-naïve adult patients with VTE (patients with active cancer were excluded) treated with a DOAC (apixaban or rivaroxaban) or VKA, from 2013 to 2018. The French national health data system (SNDS) was used. After propensity score (PS) matching for each DOAC-VKA comparison, risks of bleeding (defined as principal diagnoses of hospital stays), recurrent VTE, and all-cause mortality were compared at 6 months. Cox proportional-hazards regression was used to estimate adjusted hazard ratios of the endpoints.

Results

58137 treatment-naïve patients were included: 10775 (18.53%) VKAs, 10440 (17.96%) apixaban, and 36922 (63.51%) rivaroxaban. Patients initiating VKAs were older than those initiating apixaban or rivaroxaban (mean age in years: VKAs, 71; apixaban, 65; rivaroxaban, 60) and had a higher comorbidity burden (mean CCI score: VKAs, 1.55; apixaban, 0.91; rivaroxaban, 0.69). PS matched cohort sizes were: apixaban (n=7503) and rivaroxaban (n=9179). Crude risks of recurrent VTE per 100 patient-year (95% CI) were 4.99 (4.36; 5.70), 3.36 (2.88; 3.92) and 4.33 (4.03; 4.66) for VKAs, apixaban, and rivaroxaban respectively. For bleeding, the respective crude risks were 5.21 (4.57; 5.94), 1.84 (1.49; 2.28), and 2.64 (2.41; 2.90). For all-cause mortality, the respective crude risks were 12.23 (11.26; 13.27), 4.69 (4.11; 5.34), and 2.73 (2.49; 2.99). Adjusted hazard ratios for the endpoints are presented in the table.

Conclusions

Apixaban was associated with a lower risk of recurrent VTE and bleedings requiring hospitalisation compared with VKAs. Similar trends in risk reduction for these outcomes were observed for rivaroxaban compared with VKAs but without reaching statistical significance. Both DOACs were associated with lower risk of all-cause mortality compared with VKAs.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): BMS/Pfizer alliance
Early experience utilizing bivalirudin as anticoagulation in extracorporeal membrane oxygen in coronavirus disease 2019
Authors: Jones C X J , Chen K C , Tejera C T , Reddy R R , Faber C F , Mirza S M , Ghumman W G , Rarendran V N , Chait R C
Published: October 2021

Background

Extracorporeal membrane oxygenation (ECMO) is utilized as rescue therapy in patients diagnosed with coronavirus disease 2019 (COVID-19) with refractory respiratory or cardiogenic failure. Systemic anticoagulation with heparin remains the initial choice for thromboembolism prophylaxis in ECMO-treated patients. However, heparin carries the risk of severe complications, such as heparin-induced thrombocytopenia (HIT), and acquired antithrombin deficiency. Bivalirudin has been suggested as an alternative anticoagulant since it neither requires anti-thrombin III monitoring nor triggers HIT.

Purpose

There is very limited data on the utilization of bivalirudin in patients with COVID-19 treated with ECMO. We report the clinical safety and efficacy of using bivalirudin at our institution.

Methods

We retrospectively reviewed 17 patients diagnosed with COVID-19, who were treated with ECMO from 7/31/2020 to 12/20/2020. All patients received bivalirudin for thromboprophylaxis while on ECMO support.

Results

The mean age of our study cohort was forty-five years. Thirteen patients (76.4%) were of either Hispanic or African American descent. Of the seventeen patients, six (35.3%) patients developed deep venous thrombosis and one (5.9%) patient developed pulmonary embolism. Two (11.8%) patients developed a clotted circuit that required exchange. Fifteen (88.2%) patients had hemorrhage requiring transfusion with the gastrointestinal tract as the most common bleeding site. Nine (52.9%) patients developed thrombocytopenia. Six (35.3%) patients were discharged home or to a long-term acute care center; eleven (64.7%) patients died. The average length of stay was thirty-seven days.

Conclusion

In our small case series, the rates of complications and mortality remained high while using bivalirudin as anticoagulation of choice in patients diagnosed with COVID-19 and treated with ECMO. Further studies are needed to investigate the optimal anticoagulant in this population.

Funding Acknowledgement

Type of funding sources: None.
Increased Let-7e expression is associated with long-term all-cause mortality and antiplatelet treatment in patients with type 2 diabetes mellitus
Authors: Eyileten C , Pordzik J , Jakubik D , Czajka P , Wolska M , Jarosz-Popek J , Fitas A , Nowak A , De Rosa S , Gasecka A , Cieslicka-Kaplon A , Siller-Matula J , Postula M ,   I-COMET
Published: October 2021

Background

In the light of growing prevalence of type 2 diabetes mellitus (T2DM), efforts are made to discover novel biomarkers. MicroRNAs (miRNAs-miR) are non-coding RNAs used in various processes involved in regulating gene expression which play a role in platelet function.

Purpose

To analyze the ability of platelet-derived miRNAs in prediction of mortality and response to antiplatelet treatment among T2DM-patients.

Methods

252 diabetic subjects were enrolled and were receiving either acetylsalicylic acid (ASA) 75mg (65%) or 150 mg (15%) or clopidogrel (19%). Plasma miR-126, miR-223, miR-125a-3p and Let-7e expressions were assessed by qRT-PCR and compared between the patients who survived and those who died. Median observation time was 5.9 years. Adjusted Cox-regression analysis was used for prediction of mortality. Differential miRNAs expression due to different antiplatelet treatment was analyzed.

Results

ROC curve analysis revealed increasing concentrations of miR-126, Let-7e and miR-125a-3p levels had a diagnostic ability for prediction of long-term all-cause mortality (c-index=0.75, p<0.001; 0.72, p<0.001; 0.72, p=0.001, respectively). Multivariate Cox regression model revealed high miR-126 and Let-7e expressions which were strong and independent predictors of all-cause long-term mortality (HR=5.08, 95% CI: 1.92–13.43; p=0.001; HR=5.94, 95% CI: 1.98–17.79; p=0.001,respectively). After including all miRNAs into one multivariate Cox regression model, only Let-7e was predictive of future occurrence of long-term all-cause death (HR=7.83, 95% CI: 1.2–51.1; p=0.032). MiR-126, Let-7e and miR-223 expressions in the clopidogrel group were significantly higher than in the ASA group (p=0.014; p=0.013; p=0.028, respectively).

Conclusions

Let-7e expression is a strong and independent predictor of long-term all-cause mortality among patients with T2DM. MiR-223, miR-126 and Let-7e present significant interactions with antiplatelet treatment and clinical outcomes.

Funding Acknowledgement

Type of funding sources: None. Figure 1Table 1
Machine-learning fusion approach for the prediction of atrial fibrillation onset using photoplethysmographic-based smart device
Authors: Guo Y T , Cui Y , Zhao C , Liu L , Li L , Chen M ,   mAFA investigators
Published: October 2021

Background

The mobile and wearable technology and artificial technology are rapidly developing for atrial fibrillation (AF) detection. Nonetheless, how these smart technologies combine to improve AF prediction, rather than detection, remains unclear.

Objective

To investigate a machine-learning fusion approach beyond photoplethysmographic (PPG)-based AF detection for predicting AF onset.

Methods

There are 2,120,210 individuals who used PPG-based smart devices (Huawei Technologies Co., Ltd., Shenzhen, China) to monitor their pulse rhythm from pre-mAFA study (Huawei heart study) for AF screening across China between October 26, 2018 and March 26, 2021. Two machine-learning (ML) models, short-term model and long-term mode, have been developed based on PPG continuing monitoring signals to predict AF episode at 4h or 8h before AF onset respectively, with supervised ML (XGBoost and LightGBM) techniques, and further optimized with feature extension and hyperparameter optimization, respectively. The probabilities of AF onset calculated by both short-term and long-term models with timely PPG monitoring signals would be further input into Warning Decision Module, combined with prior predicting risk of AF onset, then the real risk ratio of predicting AF onset in advance would be output by the fusion module (Figure). The predictive ability of ML models, classified by time to last AF onset, has been validated among individuals involving in AF screening from pre-mAFA study between March 19 to March 26, compared to identified AF by PPG monitoring.

Results

There were 6294 (mean age ± standard deviation, 51.6±16.0 years old, 5439 male) individuals with identified AF, with total 142,518 identified AF episodes by PPG. The 107,864 identified AF were utilized to validate ML fusion approach for the prediction of AF, given effective PPG monitoring signals before identified AF episodes for ML models. There were 443,630 PPG monitoring signals before identified AF episodes and 563,309 non-AF PPG monitoring signals of ML models.

The sensitivity of ML fusion approach for the prediction of AF onset was 94.04%, the specificity of 96.35%, and the recall of 94.04%, respectively (Table). When time to last AF onset over 24 hours, the sensitivity of ML fusion approach for AF onset at 8h in advance was 85.73%, specificity of 96.62%, and recall of 85.73%, respectively (Table).

Conclusion

The ML fusion approach based on PPG-smart devices provided the effective early 'alters' of AF onset in advance in this large cohort, which may help the early 'upstream' management of AF.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National HealthCare of China (20BJZ26)