bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular effects and benefits through Helical stent implantation vs. conventional stenting: Methodology and initial Results of The MIMICS FLOW investigator-initiated randomized controlled trial
Authors: Rammos C , Messiha D , Petrikhovich O , Akan B , Fakea S , Sacirovic M , Lortz J , Rassaf T
Published: November 2023

Aims

Endovascular treatment is the primary revascularization strategy for symptomatic peripheral artery disease (PAD), which not only restores tissue perfusion but also affects local lower limb arterial endothelial function. Endothelial dysfunction is the pathophysiologic principle involved in the progression of atherosclerosis and is a prognostically relevant cardiovascular biomarker. A helical stent with a unique 3D helical geometry promotes laminar swirling blood flow elevating wall sheer stress, providing superior hemodynamic advantages and excellent clinical performance as compared to conventional stenting. The potential impact on endothelial homeostasis and the detailed mechanisms following a biomimetic or conventional stent are unknown. To this aim we now determined the effect of the Biomimics or a conventional stent on endothelial and vascular function in symptomatic PAD.

Methods

The MIMICS-FLOW is an investigator-initiated single-blind, randomized controlled trial (NCT05447052). The influence of novel stent-platforms with improved hemodynamic capabilities with respect to vasomotion of the vessel wall, vascular function and vascular compliance was measured by flow-mediated dilation (FMD) and arterial stiffness indices. Vascular function was determined in 70 PAD patients, Rutherford 2, 3 and 4 randomized to a helical stent and the conventional straight nitinol stent before and after lower limb intervention with a one-month follow-up in the nonstenotic segment of the proximal SFA. Perfusion indices, TLR rate and primary patency were assessed.

Results

The methodology and initial results regarding endothelial function after 1 month will be presented at ESC. In brief, 70 Patients aged 67 years were 1:1 randomized to each group prior to stent implantation in the SFA. Rutherford and PACSS class and target lesion locations were balanced between groups. One patient in the helical and 2 patients in the Straight group required a reintervention. A higher improvement in SFA FMD was observed in the helical group as compared to conventional stenting (p<0.05). Importantly, this effect was mirrored also by a greater increase in brachial FMD in the helical vs. conventional group (p<0.05). No impact was observed between groups regarding arterial or aortic stiffness.

Conclusions

Our RCT data provide evidence for an improved vascular function through swirling flow with superior hemodynamics following a helical stent implantation. These findings support the concept for a better mechanistic understanding to enhance endovascular treatment strategies in PAD.
Gut-microbiota-derived phenylacetylglutamine induces oxidative stress in endothelial cells via a NOX2-dependent pathway
Authors: Allemann M , Saeedi Saravi S S , Lee P , Beer J H
Published: November 2023

Introduction

The gut microbiota-derived metabolite phenylacetylglutamine (PAG) is clinically and mechanistically linked to cardiovascular disease (CVD)(1). Here, we aim to identify the effect of PAG on endothelial cells and elucidate the underlying molecular pathways.

Methods

We treated human aortic endothelial cells (HAEC) at a dose of 100 µM PAG (a concentration which can be observed in vivo) for 72h. As a positive control, cells were treated with H2O2 for 1h. For the determination of reactive oxygen species (ROS) formation, we used the CellROX Green assay with subsequent fluorescence microscopy. For signaling studies, protein expression levels of the NADPH oxidases NOX2 and NOX4 as well as the transcription factor NF-kB were determined by western blot analyses.

Results

Our studies showed that PAG treatment for 72h significantly increased the fluorescence intensity after CellROX Green staining (p<0.0001). Concomitantly, our immunoblotting results revealed that NOX2 (p<0.01) and NF-kB (p<0.001) protein levels were upregulated, whereas NOX4 remained unchanged in response to PAG.

Conclusion

We conclude that PAG-induced oxidative stress in endothelial cells is mediated by a NOX2 and NF-kB but not by a NOX4 dependent pathway. This study is a first step towards better understanding the molecular mechanisms of cellular responses to the gut microbiota-derived metabolite PAG.
Impact of baseline thrombocytopenia on bleeding and mortality after Venous thromboembolism: from the COMMAND VTE Registry-2
Authors: Ito S , Hamaguchi T , Kitano M , Yamaji Y , Fukuda H , Nakane E , Yamashita Y , Morimoto T , Kimura T , Inoko M
Published: November 2023

Background and Aims

The impact of baseline thrombocytopenia on the long-term clinical outcomes has not been clarified in patients with venous thromboembolism (VTE) during the direct oral anti-coagulant (DOAC) era.

Methods

This study sought to evaluate an association of baseline thrombocytopenia with major bleeding, recurrent VTE, and mortality risk in patients with VTE. This study included 5173patients from the COntemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND-VTE) Registry-2. Thrombocytopenia was defined as platelet count of <150×109/L and was classified into moderate/severe (<100×109/L) and mild (≧100-<150×109/L), based on the previous reports.

Results

At 5 years after index admission, the moderate/severe thrombocytopenia group had a significantly higher cumulative major bleeding than the no thrombocytopenia group (log-rank test, p<0.001). Moreover, the moderate/severe thrombocytopenia group had a significantly higher cumulative all-cause mortality rates than the no thrombocytopenia group (log-rank test, p < 0.001).

Conclusions

Baseline platelet level could be a prognostic marker for risk stratification.
Lipoprotein(a) and risk of peripheral arterial disease, abdominal aortic aneurysms, and major adverse limb events
Authors: Thomas P , Vedel-Krogh S , F Nielsen S , Nordestgaard B , Kamstrup P
Published: November 2023

Background

Lipoprotein(a) lowering therapy to reduce atherosclerotic cardiovascular disease is currently under investigation in clinical trials, but lipoprotein(a) may also be implicated in peripheral arterial disease (PAD), abdominal aortic aneurysms (AAA), and major adverse limb events (MALE). Yet, data from general population studies are limited, and large studies are needed to determine risk in individuals with the highest lipoprotein(a).

Purpose

To test whether high lipoprotein(a) levels associate with increased risk of PAD, AAA, and MALE, and to provide genetic evidence of causality using LPA genotypes.

Methods

We included 108,146 individuals from a contemporary prospective cohort study of the general population. During a median follow-up of 8.6 years, 2,450 developed PAD, 1,251 AAA, and 489 MALE. We used a historic prospective cohort study of the general population (N=10,960) to replicate findings for MALE (N=116).

Results

High lipoprotein(a) levels and corresponding LPA risk genotypes were associated with increased risk of PAD and AAA (Figure 1). For individuals with lipoprotein(a) levels in the 100th percentile (≥143mg/dL, ≥307nmol/L), multivariable adjusted hazard ratios were 2.99 (95% confidence interval: 2.09-4.30) for PAD and 2.22 (1.21-4.07) for AAA compared to individuals with levels <50th percentile (≤9mg/dL, ≤17nmol/L). For individuals with peripheral arterial disease, corresponding hazard ratios for MALE were 2.70 (1.67-4.37) in the contemporary cohort, 8.12 (3.56-18.55) in the historic cohort, and 3.31 (2.21-4.95) in the two cohorts combined. The absolute 10-year risk of PAD and/or AAA increased with higher age and lipoprotein(a) level for both men and women and in smokers and non-smokers (Figure 2). The absolute risk increase conferred by high (100th percentile) versus low (<50th percentile) lipoprotein(a) was 2-3-fold in all categories of age, sex, and smoking status. Absolute 10-year risks were 23% and 9% in smoking women aged 70-79 years with lipoprotein(a) in the 100th percentile versus <50th percentile, and equivalent values in men were 38% and 15%. The percentage of events attributable to lipoprotein(a) >50th percentile was 11.6% for PAD and 15.0% for AAA.

Conclusion

High lipoprotein(a) levels increased risk of PAD, AAA, and MALE by 2-3-fold in the general population, opening opportunities for prevention given future lipoprotein(a) lowering therapies.Figure 1Figure 2
Lifetime risk of developing peripheral arterial disease: a nationwide longitudinal study
Authors: Soegaard M , Nielsen P B , Behrendt C A , Lip G Y H , Eldrup N , Skjoeth F
Published: November 2023

Background

Peripheral arterial disease (PAD) presents a substantial clinical and public health burden. It remains one of the most impactful cardiovascular conditions in terms of both number of affected individuals and its impact on the individual’s survival, functional ability, and quality of life. Nonetheless, comprehensive data on the risk of developing PAD in the general population is scant.

Purpose

We aimed to quantify the lifetime risk of physician-diagnosed PAD in an unselected, nationwide population.

Methods

We conducted analyses of the entire Danish population aged 40 years and older from 2000 through 2018 using nationwide health administrative data. All individuals free of PAD were followed for up to 19 years. The cumulative incidence and residual lifetime risk of PAD adjusted for the competing risk of death was estimated by a modified survival analysis technique. Results were stratified by age, sex, and socioeconomic status.

Results

The Danish population aged 40-99 years in 2000-2018 included 4,508,932 individuals, among whom 123,479 individuals were diagnosed with PAD during follow-up. The overall lifetime risk from age 40 years during the remaining lifetime was 19.9% (95% CI 19.8%-20.2%). Lifetime risk was higher in men than in women (22.7% vs. 17.8%) and among individuals living alone (22.4% among unmarried or divorced individuals vs. 19.4% among married individuals). The highest lifetime risks were observed among individuals of lower socioeconomic status, especially individuals receiving social welfare payments for whom the lifetime risk exceeded 26%. The residual risk of developing PAD fell with age; for example, a 50-year-old who had not been diagnosed with PAD would still have a 19.6% residual risk during the remaining lifetime, whereas it was 15.4% among individuals aged 70 years.

Conclusions

About one in five individuals are likely to be diagnosed and receive medical attention for PAD during their lifetime with substantial disparities among individual of lower socioeconomic status. This knowledge may be used in public health awareness campaigns and to promote effective strategies to prevent PAD and limit progression in those with the disease and ensure the highest life quality possible.
Serum proteomic profiling of carotid atherosclerosis: a population outcome study
Authors: Sabovcik F , Verheyen A , Ntalianis E , Brguljan J , Kuznetsova T , Cauwenberghs N
Published: November 2023

Background

Circulating proteins reflecting atherosclerosis may improve cardiovascular (CV) disease prediction. We applied feature selection and unsupervised clustering on proteomic data to identify proteins associated with carotid atherosclerosis and construct a protein-based classification system for prediction of CV events.

Methods

491 community-dwelling participants (mean age, 58±11 years; 51% women) underwent carotid ultrasonography and proteomic profiling (CVD II panel, Olink Proteomics). Subsequently, CV outcome was collected (median follow-up time: 10.2 years). We applied partial least squares (PLS) to identify proteins linked to carotid intima-media thickness (cIMT). Next, we assessed the association between future CV events and protein-based phenogroups derived by unsupervised clustering (Gaussian Mixture modelling) based on proteins influential in PLS.

Results

PLS marked 19 proteins as important, which were all associated with cIMT in multivariable-adjusted linear regression. 8 of the 19 proteins were excluded from the clustering due to high collinearity. Based on the 11 remaining proteins, the clustering algorithm subdivided the cohort into two phenogroups. Compared to the first (n=177), participants in the second phenogroup (n=314) presented: i) a more unfavourable lipid profile with higher total cholesterol and triglycerides and lower HDL cholesterol (P≤0.014); ii) higher cIMT (P=0.0020); and iii) a significantly higher risk for future CV events (multivariable-adjusted hazard ratio (95% CI) versus cluster 1: 2.05 (1.26 to 3.52); P=0.0093). The protein-based phenogrouping supplemented the ACC/AHA 10-year ASCVD risk score for prediction of a first CV event.

Conclusions

Phenogrouping based on a focused set of proteins related to carotid atherosclerosis identified individuals at high risk for future CV events. This approach may complement current CV risk stratification strategies.Summary of workflow and findingsCV event prediction
The impact of duration and control of type 1 diabetes mellitus on microvascular function is strongly modified by the gene for connexin 37
Authors: Pitha J , Pithova P , Cichrova M , Dlouha D , Hubacek J A
Published: November 2023

Introduction

Type 1 diabetes mellitus (T1DM) is almost inevitably accompanied by microvascular dysfunction. This could be responsible for cardiovascular events and is supposed to be caused mainly by long-term exposure to hyperglycemia. Nevertheless, relationship between duration and control of T1DM with microvascular complications can be modified by genetic factors; one of frequently discussed candidate genes is connexin37 (cx37), namely its rs1764391 (C1019>T (Pro319>Ser) polymorphism. We already observed sex specific association between cx37 polymorphism with macrovascular changes but also with retinopathy, neuropathy and diabetic foot. In the recent study, we analyzed if the impact of duration and control of T1DM on directly measured microvascular function is modified by cx37 gene polymorphism.

Methods

In 235 men and 227 women with T1DM (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years) wide spectrum of clinical, laboratory and hemodynamic parameters was measured. Establishment of microvascular function measured by photoplethysmography (detection of blood volume changes in the microvasculature in lower extremities) and calculated as Oliva/Roztocil index (ORI), was analyzed. Cx37 gene polymorphism was measured by PCR-RFLP. The correlation (Pearson’s correlation coefficient) between duration of T1DM and ORI was calculated including analysis of potential modification by control of diabetes (HbA1c) and by cx37 gene polymorphism and standardized for potential confounders (sex, age, smoking, presence of hypertension, central obesity …) by multiple regression. The analysis was conducted separately for duration of T1DM below (n=256) and above (n=206) 20 years as the linear relationship between ORI and T1DM duration tends to change accordingly.

Results

In patients with T1DM, distribution of Cx37 genotypes did not differ from the already described populations (TT/CT/CC: 9.7/44.4/45.9%). In patients with satisfactory control of diabetes (HbA1c<53 mmol/mol; n=105) we detected worsening (increase) of ORI with duration of diabetes only in TT homozygotes and CT heterozygotes for duration of at least 20 years (r=0.6, p=0.006), while in patients with unsatisfactory control (HbA1c>60 mmol/mol;n=270), we detected worsening of ORI with duration of diabetes only in CC homozygotes, both for duration 0-20 years (r=0.35, p=0.03) and for duration of at least 20 years (r=0.47, p=0.03).

Conclusion

Microvascular function in satisfactory controlled T1DM was worsening with diabetes duration only in T allele carriers of Cx37 gene, the worsening was detected only for patients with duration longer than 20 years. However, if T1DM control was insufficient, microcirculation was worsening only in CC homozygotes.
Short-and long-term clinical impact of intravascular ultrasound-guided endovascular treatment for patients with peripheral artery disease
Authors: Kodama T , Higashitani M , Ueshima D , Yamaguchi T , Fujimoto Y , Kuwabara M , Miyazaki R , Anzai H , Suzuki K , Jujo K , Murata N
Published: November 2023

Background

Intravascular ultrasound (IVUS) has become a standard procedure in coronary intervention, but it is unclear whether IVUS usage improves procedural success rate or prognosis in patients with peripheral endovascular therapy (EVT).

Methods

This study analyzed more than 2,000 consecutive patients from the TOkyo-taMA peripheral vascular intervention research COmraDE (TOMA-CODE) registry that prospectively enrolled consecutive patients with peripheral arterial disease (PAD) in 34 hospitals in Japan from August 2014 to August 2016. The primary outcome is adverse cardiac and cerebrovascular events (MACCE) and limb events including clinical target lesion revascularization (cTLR) and amputation in the median follow-up period of 10.4 month after the first EVT. The secondary outcomes are procedural success rate and major adverse limb events (MALE) in hospital setting. Every analysis was also conducted with adjusted model after propensity score matching.

Results

In enrolled 2,227 eligible cases, we compared the MACCE and limb events between 784 cases with IVUS usage and 1443 patients without IVUS usage during EVT procedure. There was no significant difference of MACCE and limb events between with and without IVUS usage during EVT procedure over 2 years. However, EVT procedure with IVUS usage contributed significantly higher procedural success rate than that without IVUS usage (98.5% vs 96.7%, p=0.02). Moreover, EVT procedure with IVUS usage contributed less MALE (1.6% vs 4.1%, p=0.02) in hospital setting than that without IVUS usage after propensity score matching. Especially, unscheduled revascularization rate in hospital was less in EVT procedure with IVUS usage than that without IVUS usage (1.5% vs 3.7%, p=0.01).

Conclusion

IVUS usage for EVT did not improve MACCE or limb events over 2-years. However, IVUS usage improved procedural success rate and contributed less MALE when limited to the period of hospitalization. IVUS usage could be recommended for EVT procedures.Table
Efficacy of Intravascular Lithotripsy (IVL) in peripheral lesions with severe calcification and its use in TAVI procedure: A systematic review and meta-analysis
Authors: Sagris M , Dimitriadis K , Soulaidopoulos S , Beneki E , Ktenopoulos N , Papanikolaou A , Tzoumas A , Lichtenberg M , Korosoglou G , Iliakis P , Tsioufis P , Aznaouridis K , Toutouzas K , Tousoulis D , Tsioufis K
Published: November 2023

Background

Heavily calcified peripheral artery lesions increase the risk of vascular complications, constituting a severe challenge for the operator. Intravascular Lithotripsy (IVL) technology disrupts subendothelial calcification by using localized pulsative sonic pressure waves and is a promising technique for patients with severe calcification in peripheral arteries.

Purpose

Our aim was to systematically review and summarize available data regarding the safety and efficacy of IVL in preparing severely calcified plaques in peripheral arteries and its use in Transcatheter Aortic Valve Implantation (TAVI).

Methods

This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL in peripheral vasculature. The diameter of the vessel lumen before and after IVL was estimated. The occurrence peri-procedural complications were assessed using a random-effects model.

Results

20 studies with a total of 1,223 patients with heavily calcified peripheral lesions were analyzed. The mean age of the cohort was 73.8 ± 8.9 years. Successful IVL delivery achieved in 100% (95% CI: 100%-100%, I2=0%), with an increase in the luminal diameter (SMD: 4.66, 95% CI: 3.41-5.92, I2=90.8%) and reduction in diameter stenosis (SMD: -4.15, 95% CI: -4.75 to -3.55, I2=92.8%), and a described low rate of complications. There was not observed any dissection in 97% (95% CI: 91%-100%, I2=81.4%), while dissections of any type (A, B, C, or D) were observed in 6% (95% CI: 2%-10%, I2=85.3%) of the patients. Several rare cases of abrupt closure, no-reflow phenomenon, perforation, thrombus formation, and distal embolization were recorded. Finally, the subgroup analysis of patients who underwent a TAVI with IVL assistance presented successful implantation in 100% (95% CI: 100%-100%, I2=0%) of the cases, with only 4% (95% CI: 0%-12%, I2=68.96%) presented dissections of any sort.

Conclusions

IVL seems to be an effective and safe technique for preparing severely calcified lesions in peripheral vessels during TAVI interventions. These results support the use of IVL for amelioration of overall outcome in high vascular risk TAVI settings.
Prognostic value of Wound, Ischemia and foot Infection (WIfI) score after lower extremities bypass surgery for peripheral artery disease in chronic hemodialysis patients
Authors: Kumada Y , Kawai N , Ishida N , Mori A , Takahashi H , Ishii H
Published: November 2023

Background

Although lower extremities bypass surgery has been commonly performed to treat peripheral artery disease (PAD) even in patients on hemodialysis (HD) as well as general population, poorer prognosis in such subjects still remains major problems compared to non-HD population. Recently, Wound, Ischemia and foot Infection (WIfI) scoring system has been developed for classification of lower extremity threatened limb to impact amputation risk. However, the utility of predictability still remain unclear in HD patients. The aim of this study is to clarify the characteristics of the WIfI score and its prognostic value after bypass surgery in such patients with PAD.

Methods

Pre-procedural threatened limb grade in consecutive 361 patients (224 HD patients and 137 non-HD patients) undergoing successfully bypass surgery were assessed using the WIfI scoring system.

Primary outcome was amputation-free survival (AFS) defined as freedom from major amputation and/or all-cause mortality. They were followed-up for 5 years.

Results

Although ischemia grade ≥ 2 was comparable between HD and non-HD patients (97.8% vs. 99.2%, p=0.74), wound grade and infection grade ≥ 2 were significantly higher prevalent in HD patients than in non-HD patients (56.7% vs. 32.8%, p<0.0001 and 53.1% vs. 30.7%, p<0.0001, respectively). The AFS rate for 5-year was 72.6%, 46.5%, 44.4% and 32.7% in wound grade 0, 1, 2 and 3 [adjusted hazard ratio (aHR) 3.67, 95% confidence interval (CI) 1.67-8.31, p=0.0009 for grade 3 vs. grade 0], and was 57.0%, 57.8%, 45.7% and 19.4% in infection grade 0, 1, 2 and 3 (aHR 2.71, 95% CI 1.35-5.32, p=0.0052 for grade 3 vs. grade 0) in HD patients, respectively. However, even in subgroup without any wound, HD patients had markedly poorer AFS (vs. 100% in non-HD, p<0.0001) compared to non-HD patients. Also in patients without any infection, similar results were obtained (vs. 95.3% in non-HD, aHR 13.7, 95% CI 3.12-60.5, p=0.0005). HD was also consistently identified as a strong risk factor for poor AFS (aHR 2.83, 95% CI 1.67-5.09, p<0.0001).

Conclusion

Wound and foot infection grade as components of the WIfI score could stratify the risk of amputation and/or mortality after bypass surgery even in HD patients. Severity of wound or infection status was higher in HD patients compared to non-HD patients, however, high risk of poor AFS even without any wound or infection should be paid attention in this high-risk population.
Early life cardiovascular risk factor trajectories and vascular aging in midlife: a 30-year prospective cohort study
Authors: Wang Y , Wang J , Du M F , Zhang X , Chu C , Wang D , Liao Y Y , Ma Q , Jia H , Hu G L , Yan Y , Sun Y , Lu Y , Mu J J
Published: November 2023

Background

Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife.

Methods

Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years. Distinct trajectories of systolic blood pressure (SBP), body mass index (BMI), and heart rate (HR) from childhood to midlife were identified by group-based trajectory modeling. Vascular aging was assessed by carotid intima–media thickness (cIMT) or brachial-ankle pulse wave velocity (baPWV).

Results

We identified 4 distinct SBP trajectories, 3 distinct BMI trajectories and 2 distinct HR trajectories from childhood to midlife. Persistently-increasing SBP, high-increasing BMI, and high-stable HR were all shown to have a positive association with baPWV in midlife. For cIMT, similar associations were observed for persistently-increasing SBP and high-increasing BMI. After further adjustment for SBP, BMI and HR at the time of vascular assessment in 2017, associations were also observed for cardiovascular risk factor trajectories accumulation with baPWV (β=0.656 (95%CI, 0.265-1.047)] and with cIMT [β=0.045 (95%CI, 0.011-0.079)] in adulthood.

Conclusions

Longitudinal exposure to individual cardiovascular risk factors from childhood to midlife and cardiovascular risk factor accumulation were associated with an increased risk of vascular aging in midlife. Our study lends support for early targeting of risk factors in order to prevent cardiovascular disease later in life.Long-term SBP, BMI, HR trajectories
Clinical effectiveness and safety of aspirin versus anticoagulation for venous thromboembolism prevention following orthopedic trauma and surgery: a meta-analysis of randomized controlled trials
Authors: Dakay D , Gallardo E
Published: November 2023

Background

The risk for venous thromboembolism (VTE) following orthopedic trauma and surgery is high. When preventive measures are not used, the odds of DVT can reach 60% within 90 days from surgery and 1.5% for fatal pulmonary embolism. Until now, consensus is not yet reached for the best pharmacologic prevention given the clinical situation. Guidelines on VTE prophylaxis vary across expert societies.

Objective

To compare the clinical effectiveness and safety between aspirin and anticoagulation in preventing venous thromboembolism (VTE) following an orthopedic trauma or surgery

Study Selection

Only randomized controlled trials (RCT) comparing aspirin and any anticoagulants as VTE prophylaxis following an orthopedic trauma or surgery were selected for review.

Methods

Pubmed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) reporting clinical outcomes of aspirin versus any anticoagulants for VTE prevention. Primary endpoint was composite of venous thromboembolism (VTE) events. Secondary endpoints were mortality, bleeding events, and wound complications.

Results

Eleven RCTs with 17,963 patients were included in the analysis. Patients receiving aspirin as VTE prophylaxis have no significant difference in terms of reducing venous thromboembolism (VTE) events (RR 1.03; 95% CI, 0.71-1.48; p = 0.88), mortality (RR 1.01; 95% CI, 0.68-1.49; p = 0.97), bleeding events (RR 0.97; 95% CI, 0.80-1.05; p = 0.38), and wound complications (RR 0.76; 95% CI, 0.50-1.16; p = 0.21), as compared to anticoagulation after orthopedic trauma or surgery.

Conclusion

There are no significant differences between aspirin and anticoagulation in terms of reducing venous thromboembolism events, mortality, bleeding events, and wound complications following orthopedic trauma or surgery.
Sexual dimorphism in peripheral blood cell characteristics relate to success of endovascular thrombectomy in acute ischemic stroke
Authors: Overmars M , Van Solinge W W , Den Ruijter H M , Van Der Worp H B , Van Es B , Hulsbergen-Veelken C A R , Biessels G J , Exalto L G , Haitjema S
Published: November 2023

Introduction

The success of endovascular thrombectomy (EVT) in acute ischemic stroke is related to stroke etiology and clot composition. The latter two may differ between women and men. An improved understanding of sex differences in EVT success may contribute to more personalized treatment. We therefore tested the hypothesis that blood cell characteristics (BCCs) related to EVT success in acute ischemic stroke differ by sex.

Methods

We analyzed electronic health record (EHR) data of AIS patients undergoing EVT at a single intervention center. Of 311 patients, 71 pretreatment erythrocyte-, leukocyte-, and thrombocyte-related BCCs from the Sapphire hematology analyzer were extracted. BCCs were sex-stratified, clustered, and analyzed based on the first principal component of the clusters. To identify BCC clusters related to successful EVT (TICI 3), Partial Least Squares Discriminant Analysis (sPLS-DA) was performed, including cross-validation and stability selection to identify stable BCCs relative to EVT success in women and men. We also related the identified BCCs to stroke etiology (cardioembolism (CE), large-artery atherosclerosis (LAA), undetermined), and controlled for known cardiovascular risk factors.

Results

Successful EVT was achieved in 69 women (51%) and 87 men (49%). Women and men differed on 21 out of 71 BCCs (pFDR-corrected < 0.05). Analyzing sex-stratified data led to lower error rates for the female model for EVT success compared to the pooled (t(192.4) = 5.9, p < 0.001), and male model (t(182.6) = -15.6, p < 0.001). In women, a higher number of reticulocytes was associated with successful EVT and CE, whereas a higher mean corpuscular hemoglobin concentration was associated with unsuccessful EVT and LAA. In men, a higher coefficient of variance of lymphocyte complexity of the intracellular structure was associated unsuccessful EVT and LAA.

Conclusions

BCCs associated with EVT success differed by sex and were related to stroke subtype. This improved understanding may contribute to more personalized treatment of acute ischemic stroke.Model performance after sex-stratifyingSex-specific BCCs relate to EVT success
Prevalence of atrial septal defects and patent foramen ovale in a large cohort of sudden cardiac death patients undergoing autopsy
Authors: Fahy L , Spanos C , Rowe S , Nehme Z , Stub D , Zentner D , James P , Pflaumer A , Connell V , Semsarian C , Ingles J , La Gerche A , Paratz E
Published: November 2023

Background

The prevalence of patent foramen ovale and atrial septal defects has previously been described in early autopsy series and transoesophageal echocardiograms as ranging from 25 to 30%. Updated pathologic data is lacking.

Methods

A state-wide prospective out-of-hospital cardiac arrest registry identified all patients aged 1 to 50 years who experienced a sudden cardiac arrest in Victoria, Australia from April 2019 to April 2022 and subsequently underwent autopsy with a cardiac cause of death identified. A comprehensive autopsy assessment was performed including visual description of any atrial septal defect and identification of probe patency of the foramen ovale.

Results

517 patients underwent autopsy in the setting of sudden cardiac death with documentation of their atrial septal status. 36 patients (6.9%) had a probe-patent foramen ovale, 2 patients (0.4%) had secundum atrial septal defects, and 2 patients (0.4%) had a simultaneous atrial septal defect and patent foramen ovale (1 of whom had undergone percutaneous repair of both lesions). 12 patients (2.3%) had a prior history of cerebrovascular accident either recorded on medical history or detected on neuropathological examination; however none of these patients had atrial septal defects or patent foramen ovale.

Conclusions

The combined rate of atrial septal defects and patent foramen ovale in a cohort of approximately 500 patients undergoing autopsy was 7.7%. None of these patients had experienced a cerebrovascular accident. This appears lower than earlier reports, and warrants further investigation in expanded cohorts of patients.
Clinical profile, treatment strategy and prognostic value of intraventricular thrombus detection
Authors: Ortiz Lozada R Y , Pozo Osinalde E , Ferrera Duran C , Fernandez Vega A , Provencio Regidor A , Zulet Fraile P , Noriega Sanz F J , Marcos Alberca P , Fernandez Jimenez R , Mahia Casado P , Gomez De Diego J J , Fernandez Ortiz A , Perez Villacastin J , Viana Tejedor A , De Agustin Loeches A
Published: November 2023

Background

The clinical course of patients with intraventricular thrombus (IVT) is highly variable. Controversy still exists about the length of anticoagulant treatment and its prognostic relevance.

Purpose

Our objective is to describe the epidemiology and clinical course of patients with IVT.

Methods

All patients with an echocardiographic finding of IVT in our tertiary hospital between 2005 and 2021 were retrospectively analyzed. Demographic, clinical, echocardiographic, and treatment variables were collected. Patients were followed-up to 24 months.

Results

A total of 195 patients with IVT were finally included. The 84.4% were male and the mean age was 65.4 ± 14.1 years. Baseline characteristics are shown in the Table. The diagnosis of IVT was mostly made in the context of an acute myocardial infarction (AMI) (55.9%), of which 60.5% had new-onset ST-segment elevation AMI and 23.5% evolved infarction. The thrombus finding was incidental in 38.0% of the cases while 5.6% debuted as stroke. Regarding the morphological characteristics, 40.5% of the thrombi were sessile, 31.2% mural shape, and 28.3% pedicled. At diagnosis, the LVEF was 38.6 ± 11.7% with an end-diastolic volume of 132.3 ± 64.2ml. Once diagnosed 86.7% of patients were on anticoagulation, 55.4% on 2PY12 inhibitor and 78.5% on acetylsalicylic acid. At 12 and 24 months, the proportion of anticoagulated patients was significantly reduced (62% and 59.4%, respectively). 24.9% continued with a P2Y12 inhibitor at 12 months and only 9% at 2 years. During follow-up, 24.4% of the patients had events at 6 months (2.4% AMI, 7.2% stroke, 2.4% systemic embolism and mortality was 14.7%). In this period there were 8.9% of hemorrhages. The proportion of ischemic events and mortality decreased at one year (5.6%) and at two years (12.1%). Complete IVT clearance was documented in 87% and the median time to resolution was 119 days [49.5-347.5]. IVT recurrence was observed in 10.7% of the cases, up to 50% detected before 2 years from diagnosis.

Conclusions

Most patients with IVT were diagnosed after an AMI. Despite current recommendations, more than 50% of patients continued anticoagulation at 2 years. A quarter developed events 6 months after diagnosis, and this proportion decreased significantly after this period. A recurrence rate of 10.7% was observed in our population.
Fractional-flow reserve use in coronary artery revascularization: a 78.897 patients systematic review and meta-analysis
Authors: Martinez Sole J , Sorolla-Romero J A , Farjat-Pasos J , Hussain B , Garg M , Chiarito M , Diez-Gil J L , Waksman R , Garcia-Garcia H , Sanz-Sanchez J
Published: November 2023

Background

Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is recommended in the guidelines of revascularization for patients presenting with coronary artery disease (CAD) with intermediate lesion severity. However, recently published studies comparing FFR-guided PCI with non-physiology guided revascularization strategies have reported conflicting result.

Methods

The PubMed and Embase databases were searched for randomized clinical trials and observational studies comparing FFR-guided PCI with non-physiology-guided revascularization strategies (angiography-guided, intracoronary imaging-guided, coronary artery bypass grafting) in patients with CAD. Data were pooled by meta-analysis using a random-effects model.

Results

26 studies enrolling 78,897 patients were included. Patients undergoing FFR-guided PCI as compared to those undergoing non-physiology guided coronary revascularization had a lower risk of all-cause mortality (OR 0.79 95% CI 0.64-0.99, I2=53%) and myocardial infarction (OR 0.74 95% CI 0.59-0.93, I2=44.7%). However, no differences between groups were found in terms of MACE (OR 0.86 95% CI 0.72-1.03, I2=72.3%) and repeat revascularization (OR 1 95% CI 0.82-1.20, I2=43.2%).

Conclusions

Among patients with CAD, FFR-guided PCI as compared to non-physiology-guided revascularization was associated with a lower risk of all-cause mortality and MI.Clinical outcomes in patients undergoingFFR-guided PCI as compared to non-physio
Validation of pressure - derived microvascular resistance reserve (MRR) by Doppler wire measurement - the impact of correction for the error of hydrostatic pressure
Authors: Koszegi Z , Dorj A , Agoston A , Uveges A , Tar B , Kest M , Szabo G T , Czuriga D
Published: November 2023

Background

The pressure-bounded coronary flow reserve (CFRpb) defines the possible CFR interval (between CFRpbmin and CFRpbmax) using intracoronary pressure data. However, its correlation to the Doppler wire measurement was reported to be poor, partly due to the non-inclusion of the hydrostatic pressure error in the calculations. Microvascular resistance reserve (MRR), a specific index of coronary microcirculation, can be calculated from CFR and intracoronary pressure data (Pa: aortic pressure, Pd: distal pressure) by the following equation: MRR= CFR; × (Pa, rest)/(pd, hyper).

Purpose

We aimed to design a prediction model of MRR using intracoronary pressure data and to validate the results against the gold-standard Doppler wire measurement.

Methods

In our study, hydrostatic pressure between the tip of the catheter and the sensor of the pressure wire was calculated by height difference measurement from a lateral angiographic view. After hydrostatic pressure error correction, the pressure-bounded MRR interval (between MRRpbmin and MRRpbmax) was determined by the aforementioned equation. In the training population, 23 actual MRRp-3D were defined within the pressure-bounded interval by hemodynamic calculations using the measured intracoronary pressure data and the angiography-based 3D anatomical features. These results were analyzed by regression analyses to find relations between the MRRpb and the actual MRRp-3D.

Results

Using the established linear relation (MRRpredicted=1.04+0.51×MRRpbmax), our prediction was tested in the population of 21 patients undergoing the gold standard Doppler wire measurements, and a significant correlation was found (r=0.54, p=0.01). If the area stenosis was included in the prediction model, the correlation had even improved (r=0.63, p=0.004). In parallel, the Bland-Altman analysis showed reduced mean differences between the predicted MRR and the MRR values determined during the Doppler wire measurement from 0.04 (±1.96SD: 0.88, –0.8) to –0.01 (±1.96SD: 0.77, –0.79). The latter prediction utilized the quadratic relation between the area stenosis in % (AS) and the ratio of the (MRRmax−MRRp-3D)/(MRRmax−MRRmin) (ratio=0.0047+0.0067×AS+0.000039×AS2).

Conclusions

The MRR can be predicted reliably by our simple model to assess microvascular function. After the correction for hydrostatic pressure error, the pressure data during routine FFR measurement (especially with the inclusion of area stenosis) provides a simultaneous physiological assessment of the macro- and microvasculature.Flow chart of the calculations
Prognosis after non-infarct related artery PCI in patients with acute myocardial infarction and multivessel disease: substudy of FRAME-AMI trial
Authors: Hong D , Lee S H , Shin D , Kim H K , Hong Y J , Joh H S , Choi K H , Park T K , Yang J H , Song Y B , Choi S H , Jeong M H , Gwon H C , Hahn J Y , Lee J M
Published: November 2023

Background

Complete revascularization either angiography-guided or fractional flow reserve (FFR)-guided can improve the clinical outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, there is concern that angiography-guided percutaneous coronary intervention (PCI) may result in unnecessary PCI of non-infarct related artery (IRA) and its long-term prognosis is still unclear.

Purpose

We sought to evaluate clinical outcomes after non-IRA PCI according to quantitative flow ratio (QFR).

Methods

We performed post-hoc QFR analysis of non-IRA lesions of AMI patients who enrolled in the FRAME-AMI trial which randomly allocated patients into either FFR-guided PCI (FFR≤0.80) or angiography-guided PCI (diameter stenosis of >50%) for non-IRA lesions. Patients were classified by non-IRA QFR values into the QFR≤0.80 and QFR>0.80 groups. The primary end point was a major adverse cardiac event (MACE), a composite of cardiac death, MI, and repeat revascularization.

Results

A total of 443 patients (552 lesions) were eligible for the QFR analysis. Of 209 patients in the angiography-guided PCI group, 30.0% (N=60) underwent non-IRA PCI despite having QFR>0.80 in non-IRA. Conversely, only 2.7% (N=4) among 209 patients in the FFR-guided PCI group had QFR>0.80 in non-IRA. At a median follow-up of 3.5 years (interquartile range 2.7 to 4.1 years), the rate of MACE was significantly higher among patients with non-IRA PCI despite QFR>0.80 than patients with deferred PCI for non-IRA lesions (12.9% vs. 3.1%; HR=4.13, 95% CI 1.10-15.57, P=0.036). Non-IRA PCI despite QFR>0.80 was associated with higher risk of non-IRA MACE than patients with deferred PCI for non-IRA lesions (12.9% vs. 2.1%; HR 5.44, 95% CI 1.13-26.19, P=0.035).

Conclusions

In AMI patients with multivessel disease, 30.0% of angiography-guided PCI resulted in unnecessary PCI for non-IRA with QFR>0.80, which was significantly associated with the increased risk of MACE than those with deferred PCI for non-IRA lesions.
The impact of coronary revascularization on coronary flow capacity assessed by serial transthoracic echocardiographic findings in patients with chronic coronary syndrome
Authors: Ueno H , Hoshino M , Sakamoto T , Matsuda K , Nogami K , Nagamine T , Hanyu Y , Hada M , Usui E , Yonetsu T , Sasano T , Kakuta T
Published: November 2023

Background

Coronary flow capacity (CFC) integrates quantitative hyperaemic myocardial blood flow and coronary flow reserve (CFR) to comprehensively assess physiological severity of coronary artery disease. This study evaluated the effects of revascularization (PCI) on CFC assessed by serial transthoracic doppler echocardiography (TDE) examinations before and after elective PCI.

Methods

A total of 177 patients with chronic coronary syndrome underwent stress TDE examinations of left anterior descending arteries (LAD) before and after PCI to assess changes in CFC. Resting and hyperemic diastolic peak velocity (hDPV) was used to calculate CFR. Using previously reported thresholds for ischemia and normal perfusion, vessels were stratified in four CFC categories: severely reduced, moderately reduced, minimally reduced CFC, and normal flow. The association between CFC increase and pre-procedural TDE parameters was studied.

Results

After PCI, fractional flow reserve (FFR) values improved in all cases (0.70, (0.62 - 0.74), P < 0.001), although 74 cases (41.8%) showed CFC decrease. Pre-PCI lower FFR, lower resting Pd/Pa, lower CFR, and lower hDPV were significant predictors for CFC increase after PCI. Lower baseline CFC, particularly in ischemic CFC defined as a composite of moderately, and severely reduced CFC was a predictor of CFC increase (P < 0.01). On multivariable analysis, pre-PCI lower hDPV, and pre-PCI ischemic CFC were independent factors predicting CFC-improvement, while pre-PCI wire-based physiological data including FFR were not significantly associated with CFC improvement.

Conclusions

About a half of successful LAD PCI resulted in an increase in CFC. Preprocedural TDE-derived parameters including hDPV and CFC may help identification of lesions that benefit from revascularization with respect to an increase in coronary flow capacity. Further studies are needed to elucidate the effect of CFC improvement on prognosis.Effect of preprocedural CFC after PCI
Predictors of successful post-PCI optimization in vessels with post-PCI fractional flow reserve <0.90: findings from the FFR REACT trial
Authors: Neleman T , Ziedses Des Plantes A C , Scoccia A , Groenland F T W , Van Zandvoort L J C , Ligthart J M R , Witberg K T , Boersma H , Nuis R J , Den Dekker W K , Diletti R , Wilschut J , Van Mieghem N M , Daemen J
Published: November 2023

Introduction

Recent studies demonstrated a strong relation between suboptimal post-PCI fractional flow reserve (FFR) and clinical outcome. The feasibility of post-PCI FFR optimization and its impact on future clinical outcome remains topic of debate.

Purpose

The aim of the present substudy of the FFR REACT trial was to identify predictors of 1) absolute FFR increase following optimization and 2) successful functional optimization (final FFR ≥0.90).

Methods

The FFR REACT trial was a single-center, investigator initiated, randomized controlled trial including patients with (un)stable angina or non-ST segment elevation myocardial infarction and angiographically successful PCI. Following a post-PCI FFR <0.90, patients were randomized to intravascular ultrasound (IVUS)-guided optimization according to a dedicated optimization protocol (intervention arm) or no further treatment (control arm). In case of PCI optimization, FFR and IVUS were repeated to evaluate the optimization result. The present analysis included all patients randomized to IVUS-guided optimization, who actually underwent PCI optimization, and who had pre- and post-optimization FFR values available. We performed multivariate linear and logistic regression models to identify predictors of absolute FFR increase and FFR ≥0.90 following optimization.

Results

A total of 145 patients were allocated to the IVUS-guided optimization arm with 152 vessels having a post-PCI FFR <0.90 (mean post-PCI FFR: 0.83±0.05), of which 104 vessels (68.4%) underwent additional treatment after IVUS evaluation. Paired FFR measurements (pre- and post-optimization) were available in 100/104 optimized vessels. The mean absolute change in FFR was 0.03±0.06 (p<0.001), and 20/100 (20%) vessels achieved a final FFR ≥0.90.

Both left anterior descending arteries (LAD) (mean change = -0.033, 95%CI -0.055- -0.010, p=0.004) and higher post-PCI FFR values (mean change per 0.01 unit increase = -0.005, 95%CI -0.007 - -0.004, p<0.001) were associated with lower changes in FFR following optimization.

Independent predictors of achieving a final FFR ≥0.90 were higher post-PCI FFR values (OR 1.26 per 0.01 unit increase, 95%CI 1.06-1.51, p=0.009) and non-LAD vessels (OR 5.72, 95%CI 1.73-18.94, p=0.004).

Conclusions

Within the FFR REACT trial, we observed that the likelihood of improvement in final FFR values was driven by the initial post-PCI FFR values (before optimization) and the location of the target vessel, with non-LAD lesion location being a significant predictor of FFR increase.