bluuebunny/crossref_metadata_2025 huggingface dataset:
Unlocking equity: assessing for gaps in cardiovascular guidelines for pregnant women
Authors: Ekpo E , Elmore J , Uddin P
Published: October 2024

Introduction

Cardiovascular disease is the primary contributor to pregnancy-related fatalities in the United States, displaying a gradual rise over the years. Pregnancy introduces unique physiological changes that can impact pre-existing cardiovascular conditions and trigger new complications. Considerable inequalities in pregnancy-related mortality built on race and ethnicity are unmistakable, with the highest rates observed in black non-Hispanic women.

Purpose

This study aims to evaluate current gaps in racial/ethnic minority participation in randomized control trials (RCTs) cited in major cardiology guidelines.

Methods

Citations in the 2018 ESC Guidelines for the Management of Cardiovascular Diseases During Pregnancy were evaluated for RCTs. The American Heart Association and American College of Cardiology guidelines were also examined. Manuscripts and supplementary data were examined for participant-level racial or ethnic data, including age, race, and ethnicity.

Results

Thirteen RCTs, representing 20,665 participants, spanning the period from 2002 to 2017, were reviewed. European guidelines referenced thirteen of the RCTS, while American guidelines referenced two RCTs. The average age of participants was 31 years old. Most of the trials were conducted in Europe (46%). Forty-six percent of RCTs reported race/ethnicity breakdowns, with pooled participation showing a majority of non-Hispanic white participants (76.7%), with limited representation from other racial groups (table). Eight trials focused on hypertension, two on venous thromboembolism, and one on heart failure.

Conclusion

Pregnant women are frequently excluded from RCTs due to concerns about potential harm to the developing fetus. Consequently, current guidelines lack robust RCTs tailored to pregnant women with various cardiovascular diseases. The underrepresentation of ethnic minorities in cardiovascular disease trials contributes to a scarcity of evidence-based recommendations for managing these conditions during pregnancy and postpartum. Future clinical practice guidelines should advocate for a more personalized and evidence-based approach to managing cardiovascular diseases in pregnancy.
Thrombus aspiration in people living with HIV- a night mare for interventionist
Authors: Nataraj Setty H , Sridhar L , Rahul P , Jayashree K , Chethan K
Published: October 2024

Background

Cardiovascular disease, particularly atherosclerosis, and its complications are a growing cause of morbidity and mortality among individuals living with human immunodeficiency virus (HIV) in the post-antiretroviral therapy era. The role of thrombus aspiration combined with primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) within this population remains contentious. While PCI is the preferred strategy for immediate revascularization in acute STEMI, challenges persist, with about 30% of patients experiencing persistent chest pain and ST-segment elevation despite achieving TIMI III flow in the culprit vessel.

Methods

We conducted a prospective observational study spanning from January 2015 to September 2023, involving ten consecutive HIV-infected patients presenting with STEMI to our acute coronary care unit. The study encompassed an analysis of baseline clinical characteristics, response to fibrinolytic therapy, angiographic findings, thrombus aspiration using the Export Aspiration Catheter, and the outcomes of percutaneous coronary intervention (PCI). Patients were closely monitored for in-hospital outcomes and followed up for five years, during which they received adjuvant highly active antiretroviral therapy (HAART).

Results

The mean age of the patients was 46 years, lower than their uninfected counterparts. Most patients presented with a lower Killip class, indicating favorable outcomes. CD4 count distribution showed variability, with ten patients undergoing rescue angioplasty with thrombus aspiration using the Export Catheter. The cohort was followed for five years, receiving consistent HAART therapy.

Conclusion

HIV-associated atherosclerosis presents a considerable health burden, characterized by distinctive non-calcified and inflammatory plaques vulnerable to rupture. Thrombus aspiration during PCI emerged as a valuable strategy, reducing thrombotic burden and contributing to improved clinical outcomes in people living with HIV.
Cardiac biomarkers can detect and track subclinical HIV-associated myocardial disease in newly diagnosed people living with HIV
Authors: Robbertse P S , Doubell A F , Esterhuizen T M , Herbst P G
Published: October 2024

Background

Cardiovascular disease (CVD) in people living with HIV (PLWH) remains poorly understood, and the profile of disease differs between high-income and low- and middle-income settings[1]. Subclinical cardiovascular abnormalities may be present at the time of HIV diagnosis and serve as potential substrate for future CVD[2]. Biochemical markers are fundamental in cardiac evaluation, and various novel assays have recently been discovered.

Purpose

To assess the presence and evolution of subclinical myocardial disease, we prospectively assessed the hearts of newly diagnosed PLWH and matched, HIV-uninfected controls using cardiac biomarkers and correlated our findings with cardiovascular magnetic resonance imaging (CMR).

Methods

Newly diagnosed, antiretroviral treatment (ART) naïve PLWH were recruited along with HIV uninfected, age- and sex-matched controls in the Western Cape Province of South Africa. All participants underwent measurement of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2 (sST2), Galectin-3, and a CMR study with multiparametric mapping. The HIV group started ART and was re-evaluated 9 months later. The cardiac biomarkers and their correlation with CMR parameters were evaluated in, and between groups.

Results

Compared with controls (n=22), hs-cTnT (4.0 ng/l vs 5.1 ng/l; p=0.004) , NT-proBNP (23.2 ng/l vs 40.8 ng/l; p=0.02), and Galectin-3 (6.8 ng/ml vs 9.0 ng/ml; p=0.002) were all significantly higher in the ART naïve group (n=73). After 9 months of ART, hs-cTnT (5.1 ng/l vs 4.3 ng/l; p=0.02) and NT-proBNP (40.8 ng/l vs 28.5 ng/l; p=0.03) both decreased significantly, and a trend of decrease was seen in sST2 (16.5 ng/ml vs 14.8 ng/l; p=0.08). Galectin-3 did not demonstrate decrease over time (9.0 ng/ml vs 8.8 ng/ml; p=0.6). The cardiac biomarkers that showed the best correlation with CMR measurements native T1, T2, and ECV, were NT-proBNP (rs≥0.4, p<0.001) and Galectin-3 (rs≥0.3, p<0.01).

Conclusion

Our cardiac biomarker data supports the presence of subclinical myocardial injury, remodelling, and fibrosis at HIV diagnosis and ART had a positive influence on these blood markers. It remains unclear if the underlying pathological processes were fully addressed by ART. The elevation of Galectin-3 despite ART may be indicative of ongoing cardiac remodelling that may incur future risk of CVD, and necessitates further study. The ability of cardiac biomarkers to detect and track tissue abnormalities diagnosed with CMR, showed promise. With additional research, this could lead to improvements in screening and monitoring myocardial abnormalities, even in CMR-limited settings.
Pericoronary adipose tissue computed tomography attenuation (PCAT) as a marker of premature CVD in asymptomatic people living with HIV (PLWH) without traditional risk factors: H-ART to heart study
Authors: Manmathan G P R , Wardill T , Abdi Z , Ngwu N , Johnson M A , Wong D , Rakhit R D
Published: October 2024

Background

Controversy exists regarding the contribution of HIV, ART or traditional risk factors to CVD risk in PLWH. The H-ART to Heart study investigates the prevalence of subclinical CVD in asymptomatic PLWH without cardiovascular risk factors compared to negative controls(-).

Vascular inflammation inhibits local adipogenesis in pericoronary adipose tissue (PCAT) and thus can be detected on coronary computed tomography angiography (CTCA) as an increase in CT attenuation of PCAT surrounding the proximal right coronary artery (RCA).

Methods

This cross-sectional study compared PLWH aged 35-55yrs (diagnosed >10 yrs, on ART) to matched controls. Included were Caucasian men who have sex with men(MSM) and Black African/Caribbean women (BW) with traditional risk factors excluded (hypertension, hyperlipidaemia, diabetes, kidney disease, smoking, depression, inflammatory conditions, etc.).

Detailed vitals, 10 year CVD risk calculation (Q-RISK 3) were recorded. CTCA were performed with novel analysis using PCAT to assess for coronary inflammation (Figure 1.)

Results

98 participants were recruited (49M; 51 PLWH). Mean Q Risk 3 (10yr CVD risk - %) was low across the groups (HIV+MSM 4.65±2.1, HIV-MSM 3.88±2.7;p=0.29; HIV+BW 2.03±1.3, HIV-BW 1.38±0.98 p=0.66).

79 participants (42 PLWH; 37 controls) completed a CTCA with only 2 PLWH having clinically significant disease (CAD-RAD 3+ ie. >50% luminal stenosis) and none in the control group. (p=0.49)

The CT scans of 69 patients were assessed for peri-coronary adipose tissue (PCAT) density, 2 were ruled out due to a small non-dominant RCA. The PCAT density of PLWH was higher than that of the controls (-71.2±27.6 vs -75.5±30.3 P=<0.05).

Multivariate linear regression demonstrated that HIV status was an independent predictor of coronary inflammation (p=0.037) after adjusting for age, gender and BMI.

Conclusion

PWLH without traditional CV risk factors did not have significant evidence of more clinically relevant stenosis than controls on CTCA. However PCAT demonstrated a higher signal of coronary inflammation, despite stable disease, compliance with ART and low CVD risk scores. PLWH remain at risk of CV disease, this study supports the rationale for early preventative strategies for CVD prevention in PLWH.PCAT showing HIV inflammation Vs Control
Association of a history of acute kidney injury with major adverse cardiovascular events in chronic kidney disease patients
Authors: Tyl B , Costa A , Vora P , Farjat A , Sandrak P , Nadarajah R , Wanner C , Wilson D , Wu J , Gale C , Rossignol P
Published: October 2024

Background/introduction

Acute kidney injury (AKI) is strongly associated with major adverse cardiovascular events (MACE), particularly heart failure, in both general and critically ill populations. A recent study questioned whether this association holds true only for patients without chronic kidney disease (CKD).

Purpose

To evaluate the association of a history of AKI with MACE in a large real-world CKD population defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.

Methods

A retrospective cohort study was conducted using Merative® Explorys electronic health records (>54 million patients) from Jan 2010 to Dec 2019. Six cohorts of CKD patients (diagnosed or not) were created, one for each stage (1-5). Patients were required to have two consecutive abnormal eGFR, uACR/uPCR results within 3-18 months to determine CKD stage, to have at least a 12-months lookback period, and no history of end-stage kidney disease. CKD classification was not mutually exclusive (individual patients could contribute to multiple stages). Index date was the date of the second abnormal test. History of AKI was defined using ICD diagnosis codes, not through biological changes. We followed each patient until the occurrence of a composite of MACE including death, coronary events [acute coronary syndrome + coronary revascularization], any stroke, hospitalization for heart failure, or loss to follow-up, or for up to 5 years. We used multivariable Cox proportional hazards regression to estimate associations between the history of AKI and the risk of MACE during follow-up, adjusted for the following confounders: age, sex, ethnicity, systolic blood pressure, eGFR, BMI, CV history, diabetes, and any CKD diagnosis at baseline.

Results

Most of the 969,394 patients included in at least one CKD stage cohort were in stage 3a (see table) and Caucasian. Mean ages were 57-75y and 42%-64% were females across the 5 CKD stages. The prevalence of pre-existing CV disease increased from 24% in stage 1 to 57% in stage 4. The proportion of patients with a history of AKI increased from 4% in stage 1 to 36% in stage 4, as well as, the proportion of patients with a ICD code for CKD diagnosis at baseline (3% to 44%).

The 5-year incidence of the composite of MACE increased from 25.1% in stage 1 to 65.8% in stage 5. Death was the most frequent event across all stages. In multivariable analysis, a history of AKI was associated with increased risk of MACE (hazard ratios, HR 1.19 to 1.32), all-cause death (HR 1.12 to 1.86), and hospitalization for Heart Failure (HR 1.59 to 1.98) for all CKD stages, and coronary events for stage 2 to 5 (HR 1.14 to 1.22), but not stroke.

Conclusion

Patients with CKD and a history of AKI are at higher risk of adverse CV outcomes, especially hospitalization for heart failure. This study suggest that these patients should receive cardio -protective intervention.
Anemia in patients with chronic kidney disease and its association with cardiac abnormalities
Authors: Gomez-Aviles P , Gomez-Cruz J R , Almeda-Valdes P , Guerra E C , Martinez-Dominguez P , Jimenez-Hernandez M
Published: October 2024

Introduction

Chronic kidney disease (CKD) is a pathology characterized by multisystemic comorbidities, predominantly associated with cardiovascular disease and anemia. However, the precise association between the degree of anemia and the development of cardiac abnormalities in patients with CKD undergoing hemodialysis remains unclear.

Purpose

To determine the association between the degree of anemia and cardiac abnormalities in patients with CKD receiving hemodialysis treatment.

Methods

A cross-sectional multicenter study that included individuals with CKD undergoing hemodialysis was conducted. Electronic medical records containing information regarding medical conditions and pertinent laboratory parameters was collected, and cardiac function was determined using echocardiography. A Spearman rank correlation analysis was conducted to evaluate the associated between the degree of anemia and echocardiographic parameters, with significant set at p <0.05.

Results

Ninety-nine individuals were included, with a median age of 48 years. The population was categorized based on hemoglobin (Hb) levels into non/mild anemia (Hb >10 mg/dL) and moderate/severe anemia (Hb <9.9 mg/dL) groups (table). Significant differences were observed in left ventricle (LV) posterior wall thickness (10mm in non/mild vs. 11mm in moderate/severe, p<0.015), left atrial (LA) volume (34 mL/m2 in non/mild vs. 39 mL/m2 in moderate/severe, p<0.007) and left ventricular ejection fraction (LVEF) (59% in non/mild vs. 55% in moderate/severe, p<0.025). Negative correlations (figure) were observed between Hb levels and LV mass index (r= -0.21, p= 0.03) and pulmonary artery systolic pressure (PASP)(r= -0.27, p= 0.006).

Conclusion

The degree of anemia demonstrated an association with cardiac abnormalities, as evidenced by alterations in echocardiographic parameters such as LVEF, LA volume and PSAP. This study underscores the importance of further prospective investigations to enhance early identification and stratification of anemia in patients with CKD aiming to mitigate further cardiac complications.Clinical demographics tableScatter plots with correlation graphs
Efficacy and safety of intravenous iron therapy in heart failure patients with iron deficiency: a systematic review and meta-analysis of randomized controlled trials
Authors: Abouzid M , Tanashat M , Khlidj Y , Abuelazm M , Ramadan A , Altobaishat O , Aboutaleb A , Ullah I , Abdelazeem B
Published: October 2024

Background

Heart failure is a diverse life-threatening condition with complex biology and demanding therapeutic goals. Even when anemic patients are excluded, up to 59% of heart failure patients have low ferritin levels, making them especially vulnerable to iron deficiency.

Purpose

To assess the complete data derived from Randomized controlled trials concerning the benefits and safety of IV ferric carboxymaltose therapy among patients with heart failure with iron deficiency.

Methods

A systematic review and meta-analysis of randomized controlled trials obtained from PubMed, WOS, SCOPUS, EMBASE, and Cochrane up to August 31, 2023. We used RevMan V. 5.4 to pool dichotomous data using a risk ratio (RR) with a 95% confidence interval (CI).

Results

We included 14 randomized controlled trials with a total of 6,626 patients. The IV iron group was favored over the control group in reducing hospital admissions for heart failure (first event) (RR= 0.83, 95% CI 0.71 to 0.97; p = 0.02) and (total events) (RR= 0.81, 95% CI 0.74 to 0.89; p < 0.0001). Also, the iron group had a 21% lower risk in terms of cardiovascular death and hospital admission for HF (number of events, rate per 100 patients in a year) (RR= 0.79, 95% CI 0.74 to 0.85; p < 0.00001). Concerning the adverse events, both ferric carboxymaltose and ferric derisomaltose showed a beneficial effect in reducing the cardiac disorder (RR= 0.81, 95% CI 0.76 to 0.87; p <0.0001), and (RR= 0.82, 95% CI 0.71 to 0.95; p = 0.009), respectively.

Conclusion

IV iron infusion in patients with heart failure has a favorable safety profile. It reduces total hospitalizations for heart failure and cardiovascular mortality, with no effect on all-cause mortality, cardiovascular mortality alone, or first-time hospitalization for heart failure.
Zibotentan in microvascular angina: a randomized, placebo-controlled, crossover trial
Authors: Morrow A , Berry C
Published: October 2024

Background/Introduction

Microvascular angina is a chronic condition characterized by abnormal myocardial blood flow leading to ischemic symptoms. Endothelin-1, a peptide secreted by endothelial cells, is a highly potent constrictor of the human coronary arterioles. Microvascular angina is associated with elevated circulating concentrations of endothelin-1, and prolonged exposure to ‘excess’ endothelin causes vasoconstriction and vascular remodelling. The chronic elevation of circulating endothelin-1 in microvascular angina may be influenced by genetic factors.

Purpose

Zibotentan, the most selective antagonist of the endothelin A receptor with no off-target binding to the endothelin B receptor, was evaluated in oncology trials and did not improve survival. We identified zibotentan as a potential disease-modifying therapy for patients suffering from microvascular angina. We hypothesized that zibotentan 10 mg daily for 12 weeks in addition to background medical therapy could be an efficacious and safe treatment for patients with microvascular angina. We further hypothesized that the SNP regulator of EDN1 gene expression, rs9349379 (G allele), could be a novel theragnostic biomarker.

Methods

The trial involved a prospective, multicentre, randomized, double-blind, placebo-controlled, sequential crossover design to assess the effects of zibotentan 10 mg or matched placebo, once daily for 12 weeks. The primary outcome was treadmill exercise duration (seconds) using the Bruce protocol. The secondary outcomes included exercise test parameters, health status questionnaires, safety (frequency and severity of severe adverse events (SAEs) and adverse events), feasibility (withdrawal rate), and biomarkers of efficacy (pharmacokinetics, pharmacodynamics).

Results

The study found no significant difference in exercise duration with zibotentan (-4.26 seconds; 95% CI: -19.60 to 11.06; P=0.5871). There was no effect on the secondary outcomes. However, for exploratory (mechanistic) outcomes, zibotentan increased plasma big endothelin-1, endothelin-1, and global myocardial blood flow, while reducing hemoglobin, diastolic, and systolic blood pressure (all p<0.001). Adverse events were more common during the zibotentan period (60.2%) compared to placebo (14.4%, p<0.001).

Conclusion(s)

In conclusion, daily administration of 10 mg zibotentan for 12 weeks did not enhance exercise duration and was commonly associated with adverse effects related to fluid retention. Further trials exploring lower zibotentan doses in combination with agents to mitigate fluid retention, and longer treatment durations, are warranted.
Lipid-lowering therapy with Inclisiran in the real-world setting: initial data from a national health care service
Authors: Zafrir B , Naoum I , Aker A , Saliba W
Published: October 2024

Introduction

Inclisiran, a first-in-class siRNA enabling long-term inhibition of PCSK9 synthesis, demonstrates good safety and efficacy profile in randomized clinical trials. Challenges for real-life use of inclisiran include limited access to therapy, injections by medical staff, lack of cardiovascular outcome data, and concern from adverse effects considering the novel mechanism and long-term activity. Real-life data on the potential to attain lipid-goals and reduce treatment gaps is lacking. We investigated the implementation of inclisiran in real-world clinical setting in Israel.

Methods

Data from a nationwide healthcare organization on patients initiating inclisiran therapy during the period of 3/2022-11/2023. Patients’ characteristics, efficacy, use of combination lipid-lowering therapies, and attainment of low-density lipoprotein cholesterol (LDL-C) goals, were evaluated.

Results

Inclisiran was initiated by 503 patients (57% women; mean age 66±11 years). Atherosclerotic cardiovascular disease was present in 54%, and peak historical LDL-C levels >190 mg/dL documented in 64%. Prior exposure to PCSK9 monoclonal antibodies was evident in 28%. Follow-up lipid profile >2 months after filling first prescription, was available in 397 patients (347 with ≥2 injections). In patients treated by inclisiran only (n=254), median LDL-C reduction from peak historical levels was 57% (IQR, 48%-67%), and from pre-injection levels 40% (19%-54%). In those with concomitant oral lipid-lowering therapies (n=143), median LDL-C reduction from peak levels was 66% (IQR, 55%-73%), and from pre-injection levels 46% (23%-59%) (Figure). LDL-C <70 mg/dL was attained by 39% and LDL-C <55 mg/dL by 21.9%. Of those treated with concomitant statin therapy, 38% attained LDL-C <55 mg/dL. Overall, 6.5% did not persist with inclisiran therapy after initial injection.

Conclusions

In real-life practice, inclisiran showed good efficacy with positive short-term adherence. However, attainment rates of lipid-goals were suboptimal due to limited use of combination lipid-lowering therapy and high-rates of severe hypercholesterolemia in our patient population cohort.Waterfall Plot of LDL-C (%) Reduction
Efficacy of combination lipid lowering therapy in achieving low density lipoprotein cholesterol targets after one month of event in patients with acute coronary syndrome
Authors: Mahajan K , Mohite K , Himral S K , Dsouza S , Chandel P , Kapoor A , Patel P , Yadav R , Sharma J B , Puri R
Published: October 2024

Introduction

Rapid reduction in low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of recurrent events in patients with acute coronary syndrome (ACS) with benefits proportional to LDL-C reduction. Early use of combination lipid-lowering therapy (LLT) is therefore recommended. Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) combined with high-intensity statins (HIS) improve LDL-C goal attainment but are unaffordable for many patients in India and worldwide.

Purpose

We share our experience with the use of dual RE (rosuvastatin plus ezetimibe) and triple REB (rosuvastatin plus ezetimibe and bempedoic acid) combination LLT in patients admitted with ACS.

Methods

All ACS patients admitted to our institute over one year (January 2023 to December 2023) were considered in this retrospective analysis. Those with unavailable lipid profile reports, either at the time of ACS or at 1-month follow-up, were excluded. Clinical and laboratory details were obtained from hospital records. The primary objective was to assess the percentage change in LDL-C levels from index event to 4 weeks follow-up.

Results

A total of 299 patients were included, out of which 60 were on HIS alone, 71 were on RE, and 168 were on REB (Figure). The majority (99%) of patients in the REB group were statin naïve, compared to the other two groups. The baseline mean LDL-C levels at the time of the index event were 95.3+30.5, 103.2+39.6, and 115.6+32.9 mg/dl, respectively (p<0.001) (Table). The mean LDL-C levels at four weeks post-ACS reduced to 52.9+21.2, 45.9+20.5, and 43.7+15.4 mg/dl, respectively (p<0.01). The percentage reduction in LDL-C level was 44.4%, 55.5%, and 62.2%, respectively (p<0.001). REB enabled 70.8% and 95.2% of patients to achieve the Lipid Association of India, and American College of Cardiology recommended LDL-C targets of <50 mg/dl and <70 mg/dl within 4 weeks. These target levels were achieved in 67.6% and 88.7% of patients on the dual RE therapy and 50% and 81.6% of patients, respectively, on HIS alone.

Conclusion

Our study demonstrates the capacity to rapidly achieve LDL-C goals after ACS with triple REB therapy, an affordable regimen compared to costly PCSK9i therapy.Figure.Lipid lowering strategies usedComparison of study groups
Predicting 1-year atrial fibrillation risk from a patch-based ambulatory ECG monitoring without atrial fibrillation
Authors: Gadaleta M , Harrington P , Okeson A , Hytopoulos E , Turakhia M P , Steinhubl S R , Quer G
Published: October 2024

Introduction

Early identification of atrial fibrillation (AF) can enable interventions that reduce cardiovascular events. However, AF remains undiagnosed in about 10-20% of affected individuals, and paroxysmal AF often remains undetected despite the use of in-clinic ECGs, consumer smartwatch ECGs, or ambulatory ECG monitoring. We therefore investigated whether ambulatory ECG patch-based monitoring without AF can predict AF in the subsequent 1-year post monitoring.

Purpose

This study aims to validate a machine-learning model for AF prediction within 1-year post-wear, based on the observation of non-AF single-lead ECG recordings.

Methods

We considered a clinically monitored cohort of 67,296 individuals wearing multiple single-lead ECG multi-day ambulatory monitoring patches as part of real-world care. For all selected individuals, the first patch recorded no occurrences of AF and was worn for a minimum of 6.5 days. We assess the risk of future AF based on the raw ECG, heartrate variability, frequency of ectopic beats, age and gender (ECG model), which is then compared with the risk assessment by a model based on age and gender (Baseline model). We then observe AF incidence on subsequent patches worn within one year from the first patch. We evaluated the model's accuracy by observing the number of AF cases identified (or missed) among the individuals with highest risk according to the model.

Results

In the clinically monitored cohort, a total of 3463 individuals experienced AF within the next year (incidence 5.1%) after a first AF-free monitoring period of a minimum 6.5 days. The receiver operating characteristic (ROC) curve shows an area under the curve (AUC) for the ECG model of 0.75 (95% CI: [0.74, 0.76]), and for the Baseline model of 0.66 (CI: [0.65, 0.67]). When selecting the top 20% (13,459) participants with the highest risk and verifying who developed AF in the following 1-year, we obtain positive prediction value (PPV) or precision of 12% and sensitivity (recall) of 46% for the ECG model (which correctly identifies 1,594 individuals with incident AF), and of 8% and 29%, respectively, for the Baseline model (p-value<0.001). (Figure)

Conclusion

A machine learning model using as input an AF-free single-lead ECG can quantify the risk of observing AF in a population including individuals with low burdens of paroxysmal or new onset of AF within 1 year. Further research and validation are needed to enhance the interpretability and clinical applicability of the model, while prediction may be further improved with clinical AF diagnoses ascertained from other data sources. The findings of this study have important implications for the early detection and management of AF, potentially enabling earlier intervention and improved outcomes in individuals with undiagnosed AF.
Association of HbA1C with mortality and cardiovascular outcome in patients with type 2 diabetes using drugs with different hypoglycemic risk
Authors: Lin Y , Shao Y H , Huang L Y , Chen B L , Huang C Y
Published: October 2024

Background

Previous clinical trials showed that intensive glucose control did not reduce macrovascular events and mortality. It was speculated that severe hypoglycaemia contributed to these adverse outcomes. More contemporary clinical trials using newer anti-diabetic agents with less hypoglycaemic potential showed a linear relationship between major adverse cardiovascular events (MACE) and HbA1c reduction according to a meta-regression analysis.

Purpose

The aim of this study was to examine the association between clinical outcomes and HbA1c under different treatment backgrounds in the real-world setting. We hypothesised that when using drugs with minimal hypoglycaemic risk, lower HbA1c would be associated with better outcomes.

Methods

This was a retrospective population-based cohort study using a multi-centre electronic medical record database. Eligible patients were those diagnosed with type 2 diabetes between 2009 and 2020 who received non-insulin antidiabetic drugs. Patients were stratified into two groups based on the drugs received: drugs with high hypoglycaemic risk (sulphonylurea, meglitinide) and drugs with low hypoglycaemic risk (thiazolidinediones, acarbose, DPP4 inhibitors, GLP1 agonists, SGLT-2 inhibitors). Patients were excluded if they had received these drugs for less than 180 days or had received both high and low hypoglycaemic risk oral drugs simultaneously. HbA1c levels were assessed from the index date to the date of the interested outcome or the end of the study period (31 December 2021), whichever came first. The relationship between HbA1c and clinical outcomes was examined using a Cox proportional hazards model. The outcomes of interest included all-cause mortality and MACE.

Results

The study population consisted of 6,923 patients, including 3,639 high hypoglycaemic risk drug users and 3,284 low hypoglycaemic risk drug users. Patients with lower HbA1c levels during the follow-up period were older and frailer. After adjusting for baseline covariates, the association between the risk of death and HbA1c presented a U-shaped pattern, and this U-shaped association was similar in the two treatment cohorts (Table 1). On the other hand, the association between the risk of MACE and HbA1c presented a J-shaped pattern. In the high hypoglycaemic risk drug cohort, patients with the highest HbA1c levels (mean HbA1c 9.6%) were associated with a higher risk of MACE compared to the group with a mean HbA1c of 7.2% (hazard ratio [HR] 4.16, 95% confidence interval [CI] 2.07-8.37); lower HbA1c levels were not associated with a lower risk of MACE (Table 2). In contrast, in the low hypoglycaemic risk drug cohort, lower HbA1c levels were associated with a higher risk of MACE (HR 3.82, 95% CI 1.29-11.28).

Conclusion

Lower HbA1c levels were not associated with a lower risk of all-cause mortality and MACE. Furthermore, this phenomenon was independent of the hypoglycaemic risk of anti-diabetic drugs.
The effect of metformin use on the risk of atrial fibrillation in patients with type 2 diabetes: data from the UK biobank
Authors: Guo T S , Zhao C Y , Chen T , Tang M Y , Ning Y Y , Wang D L , Yuan Z Y , Li G
Published: October 2024

Objective

The present study aims to investigate the protective role of metformin against atrial fibrillation (AF) and stroke in type 2 diabetes (T2DM) patients treated with other antidiabetic medications.

Methods

We included 10,011 participants with T2DM from the UK biobank database, with a follow-up for new diagnoses of AF and stroke recorded until 2023. We employed logistic regression analysis and competing risk models to assess the association between metformin use and the incidence of AF or stroke.

Results

The cross-sectional analysis revealed that, compared with the use of other antidiabetics, metformin was associated with a lower prevalence of AF (odds ratio [OR] 0.71, 95% CI: 0.57–0.89) and stroke (OR 0.70, 95% CI: 0.56–0.86). In the competing risk model, compared to other antidiabetics, metformin may reduce the risk of AF (sub-hazard ratio [SHR] 0.86, 95% CI: 0.75–0.98) and stroke (SHR 0.62, 95% CI: 0.44–0.86) (Figure 1). Subgroup analysis indicated a significantly lower incidence of AF or stroke in patients under 65 years of age (SHRs were 0.80, 95% CI:0.67-0.96 for AF and 0.52, 95% CI: 0.34-0.81 for stroke) and in female patients (SHRs were 0.65, 95% CI:0.52-0.81 for AF and 0.53, 95% CI: 0.30-0.91 for stroke). Notably, metformin significantly reduced the incidence of AF in non-insulin users (SHR 0.80, 95% CI: 0.66-0.97) and the incidence of stroke in insulin users (SHR 0.55, 95% CI: 0.35-0.87) (Figure 2).

Conclusion

Our findings suggest that metformin use, in comparison to other antidiabetic medications, is associated with a reduced risk of AF and stroke, especially in non-insulin users for AF and insulin users for stroke.
Drug-drug interactions of empagliflozin and dapagliflozin
Authors: Stoellberger C , Finsterer J , Schneider B
Published: October 2024

Introduction

The sodium glucose co-transporter2-inhibitors dapagliflozin (Dapa) and empagliflozin (Empa), initially developed as antihyperglycemic agents, are increasingly also prescribed for non-diabetic patients with heart failure (HF). Glucuronidation by uridine-diphosphate glucuronosyltransferase (UGT)1A9 is the main mechanism of metabolism of Dapa, whereas Empa is eliminated mainly by excretion. Both Dapa and Empa are substrates of P-glycoprotein. The risk for drug-drug interactions (DDI) of Empa and Dapa is assumed to be low. Aim of this study was to summarize reports of DDI of Empa and Dapa from the literature.

Methods

Search-terms in PubMed were "drug-drug interaction" and AND "sodium glucose co-transporter2-inhibitors" OR "SGLT2" OR "dapagliflozin" OR "empagliflozin". The drugs were classified according the Anatomical Therapeutic Chemical (ATC) system. Included were randomized trials, pharmacovigilance studies, case series, case reports, studies in healthy subjects and in vivo data. The funding of the study and the disclosures of the authors were registered.

Results

In 45 reports DDI of Empa and Dapa with 29 drugs were described (Table). According to the ATC system, these were drugs for the alimentary tract and metabolism (n=5), blood and blood forming organs (n=2), cardiovascular system (n=11), genitourinary system and sex hormones (n=2), antiinfectives (n=2), antineoplastic and immunomodulating agents (n=3), musculo-skeletal system (n=2) and nervous system (n=2). The reports comprised studies in healthy subjects (n=28), case reports (n=7), case series (n=6), pharmacovigilance studies (n=2), a subgroup analysis of a randomized trial (n=1) and in vivo data (n=1). Most of the reports found no clinically relevant DDI (n=32).

Dapa and Empa both had a synergistic diuretic effect with bumetanide, and led to severe infections when combined with the interleukin-17-inhibitors secukinumab or ixekizumab. Empa administered with intravenous iron was reported to increase cell-iron availability, with lithium to reduce lithium exposure and with valproate to increase valproate exposure. Dapa administered with sacubitril-valsartan was reported to lead to severe hypotension, with linezolid to pancytopenia, with donafenib to an increased exposure to donafenib, with rifampicin to a reduction and mefenamic acid to an increase in Dapa exposure.

Of the 45 reports, 33 were funded by a pharmaceutical company marketing Dapa or Empa and 33 had authors with conflicts of interest with pharmaceutical companies marketing Dapa or Empa.

Conclusions

Most data about DDI of Empa and Dapa derive from studies in healthy subjects and from the marketing companies. The clinical relevance DDI of Empa and Dapa in polymorbid patients with polymedication is largely unknown. There is an urgent need for independent studies on DDI of these drugs in diabetic and non-diabetic patients with HF.Table
Use of new antidiabetic drugs in patients with cardiovascular diseases - real life data
Authors: Vucak J V , Corak N C
Published: October 2024

Introduction and aim

Cardiovascular diseases (CVD) are among the most common and significant complications of type 2 diabetes mellitus (T2DM). Despite significant therapeutic progress in the prevention of CVD, T2DM remains a leading cause of major adverse cardiac events (MACE). Patients with T2DM and clinical manifestations of atherosclerotic CVD, or those at high risk of developing it, should receive cardioprotective and nephroprotective medications such as GLP-1 receptor agonists (GLP-1) and SGLT-2 inhibitors (SGLT2). This study aims to determine to what extent patients undergoing treatment at the general practitioner (GP) level comply with the recommendations.

Methodology

Retrospectively, in the period January 2022 to September 2023, records in the EHR were reviewed in the five GP offices. For all patients ( ≥18 years) with DMT2, all demografic as well as data on chronic therapy, stage of chronic kidney disease (CKD), presence of any cardiovascular (CV) risk factors and/or history of cardiovascular diseases (CVD), and the therapy applied were observed.

Results

A total of 6,941 patients' data were reviewed, out of which 483 (6.96%) had a diagnosis of DMT2. Table 1. shows the characteristics of the study population. Table 2. presents the values of HbA1c according to the criteria of good, acceptable, and poor DMT2 control, as well as the CKD stage by eGFR. Among the associated comorbidities, the most common was arterial hypertension, observed in 79.5% of the participants, followed by obesity in 28.2%. In terms of the applied therapy, the majority of participants were on metformin (76.8%). There were no significant differences in body mass index (BMI) and glycemic control between the group with and without CVD. However, compared to the group without CVD, patients with both DMT2 and CVD had a higher frequency of SGLT2 inhibitors (27% vs. 18.5%) [chi²=4.336, df=1, p=0.032] and GLP-1 receptor agonists (10.7% vs. 4.6%) [chi²=6.336, df=1, p=0.012] use, but a lower frequency of metformin (67.9% vs. 81.2%) [chi²=10.510, df=1, p=0.001].

Discussion

According to current guidelines, all patients with CVD and CKD should have SGLT2 inhibitors and/or GLP-1 receptor agonists in their therapy. Comparing our study with the CAPTURE study, our patients were older and had slightly fewer associated CVD (38.7% vs. 32.9%). According to the CAPTURE study, less than 25% of patients with DMT2 in therapy have an antidiabetic medication with proven cardiovascular benefit, while in our sample, this was the case for 31.4% of the participants. This suggests that progress is being made, but it is still insufficient.

Conclusion

Over the past decade, there has been a rapid increase in knowledge regarding the appropriate treatment and management of risk factors in the population of individuals with DMT2. Although new insights are continuously incorporated into guidelines, our study shows that implementation in practice lags.
Temporal trends and regional differences of initial oral antiarrhythmic drug options in patients with new-onset atrial fibrillation: a report from the GLORIA-AF registry
Authors: Huang B , Lam H M , Ishiguchi H , Liu Y , Chao T F , Olshansky B , Huisman M , Lip G
Published: October 2024

Background

New-onset atrial fibrillation (AF) is common and antiarrhythmic drugs (AADs) are commonly used for treating such patients. However, whether there are temporal changes and regional differences in the choice of AADs in direct acting non-vitamin K oral anticoagulants (DOACs) era is less studied.

Purpose

The present study aimed to analyze the temporal trends and regional differences of initial oral AAD options in patients with new-onset AF in the GLORIA-AF registry, based on a proposed modernized classification of AADs in 2018 (Circulation, 2018, PMID: 30354657). AADs involved in the present study included traditional Vaughn-Williams Class I to Class IV AAD, Class IId AAD (digoxin), and Class VII AAD, which acts on the upstream of arrhythmia including angiotensin converting enzyme inhibition, angiotensin receptor blocker, and stains.

Methods

Temporal changes regarding the AAD use between the two phases of GLORIA-AF and regional differences of AADs choice were investigated. Factors associated with the choice of different AADs were established by multivariate logistic regression.

Results

Among the 36,617 participants in the GLORIA-AF registry, 33,208 (90.7%) were prescribed with AADs: 74.0% were rate control and 10.2% were rhythm control, and among the prescribed AADs, single and dual AADs were used in 73.3% and 24.9%, respectively. Moreover, 70.5% patients received upstream target modulators (Class VII AAD). Class IIa AADs (beta-blockers) were the most commonly prescribed AAD and slightly increased from Phase II (60.58%) to Phase III (62.91%) while the use of Class IId AAD (e.g. digoxin) decreased regardless of single or combined use. AADs use varied significantly among regions but the temporal trends and regional differences were similar with that of the overall cohort. Age, gender, comorbidities, admission signs, region, and concomitant medications (e.g. anticoagulants) were associated with the choices of different AADs.

Conclusions

In the DOAC era, new-onset AF patients receiving AAD commonly included upstream therapy. Rate control was still the dominant strategy for patients with new-onset AF but the use of Class IId AAD significantly decreased with the increased use of Class IIa AAD. The choice of AADs demonstrated significant regional differences and concomitant anticoagulants played important roles.Temporal trends in GLORIA-AFComparisons of AADs use in GLORIA-AF
Haemorrhagic risk in elderly patients with atrial fibrillation that develop low platelet count during direct oral anticoagulant treatment: insights from the ATHERO-AF study
Authors: Menichelli D , Crisanti L , Brogi T , Lip G , Pignatelli P , Pastori D
Published: October 2024

Background

Bleeding risk in atrial fibrillation (AF) patients is complex and dynamic. Among others, thrombocytopenia has been suggested as a bleeding risk factors. No data on thrombocytopenia occurring during direct oral anticoagulants (DOACs) therapy are available.

Purpose

We investigated the incidence rate of thrombocytopenia and major bleeding (MB) in AF patients on DOACs. We also investigated whether the addition of incident thrombocytopenia to the HAS-BLED score might increase its predictive value compared to baseline HAS-BLED calculation.

Methods

955 AF patients from the prospective ongoing ATHERO-AF study followed for a mean of 38.4±26.6 months. All patients were on DOACs. Thrombocytopenia was defined by a platelet count <150 x109/L registered during follow-up visits. MB events were defined according to ISTH definition and were recorded at each follow-up visit. Patients with thrombocytopenia at baseline were excluded. Multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratio (HR) with 95% Confidence interval (95%CI) for each factor in relation to bleeding risk.

Results

Mean age was 77.3±9.0 years and 40.1% were women. During a follow-up, 139 patients developed thrombocytopenia with an incidence rate of 0.8% per year. We recorded no difference between thrombin and factor Xa inhibitors. During follow-up, 179 bleedings occurred, of which 80 were major. Patients experiencing bleedings were more likely to suffer from arterial hypertension, heart failure, anaemia and had higher CHA2DS2-VASc and HAS-BLED scores. At multivariable Cox proportional hazards regression analysis, factors associated with MB were incident thrombocytopenia (HR 1.995, 95%CI 1.211-3.288), antiplatelet use (HR 2.716 95%CI 1.269-5.816) and age (HR 1.033, 95%CI 1.003-1.064). The addition of incident thrombocytopenia to the HAS-BLED score increased the predictive value of baseline HAS-BLED in patients without thrombocytopenia for MB events (AUC from 0.54 to 0.61, p=0.016).

Conclusion

Incident thrombocytopenia is associated with an increased risk of MB. The addition of incident thrombocytopenia to the baseline HAS-BLED score increased its predictive value, suggesting that continuous bleeding risk evaluation of AF patients may provide additional prognostic information compared to the baseline only.
Unfractionated heparin or low molecular weight heparin in patients with acute pulmonary embolism: a meta-analysis of randomized controlled trials
Authors: Maqsood M , Zhang R , Bangalore S
Published: October 2024

Introduction

There is limited data on the use of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) in patients admitted for acute pulmonary embolism (PE). Current ESC guidelines preferred LMWH over UFH based on extrapolated data. We aimed to compare UFH and LMWH in patients with acute PE using randomized controlled trials (RCTs).

Methods

A comprehensive literature search was performed from inception to 02/01/2024 of the PubMed database. Studies of adult patients comparing UFH to LMWH were evaluated for short-term (7-to-12 days) mortality, long-term mortality (90-days to 180-days), short-term (7-to-12 days) and long-term major bleeding (90-days to 180-days). Odds ratio (OR) with 95% confidence intervals (CI) were calculated using DerSimonian-Laird method.

Results

Of a total 2400 studies, nine RCTs with 1,996 subjects (1025 UFH and 971 LMWH) were included with mean age of 62.9 years and 48.5% males. There was no difference in short-term (OR= 0.89 [95% CI 0.44-1.82]; p=0.75; I2=0%; 6 trials) and long-term mortality (OR= 0.77 [95% CI 0.50-1.21]; p=0.26; I2=0%; 6 trials) with use of LMWH or UFH (Figure Panel A and B). Similarly, there was no difference in short-term (OR= 0.70 [95% CI 0.38-1.32]; p=0.27; I2=0%; 9 trials) and long-term major bleeding (OR= 0.92 [95% CI 0.53-1.60]; p=0.77; I2=0%; 6 trials) with use of LMWH or UFH (Figure Panel C and D). Overall, there was no evidence of publication bias using either funnel plot or eggers test (p > 0.05).

Conclusions

In this meta-analysis of 9 RCTs, there was similar efficacy and safety of UFH and LMWH in patients admitted for acute PE. However, future large-scale trials are needs to confirm these findings.