bluuebunny/crossref_metadata_2025 huggingface dataset:
Home treatment of fragile patients with acute pulmonary embolism: a subgroup analysis of the multinational home treatment of pulmonary embolism (HoT-PE) trial
Authors: Hobohm L , Anusic T , Konstantinides S.V , Barco S
Published: November 2020

Background and aims

Subgroup analyses of randomized trials and cohort studies on direct oral anticoagulants (DOACs) suggested that single direct drug treatment may be effective and safe in elderly and “fragile” patients with acute pulmonary embolism (PE). In a post-hoc analysis of HoT-PE, a prospective multicenter management trial, we studied whether early discharge and home treatment of acute PE is effective and safe in these patients.

Methods

HoT-PE enrolled patients with acute PE classified as being at low risk based on the modified Hestia criteria and the absence of right ventricular dysfunction. The primary efficacy outcome was symptomatic recurrent VTE, or PE-related death within 3 months of enrolment. The safety outcome included major bleeding. Fragility was defined as age >75 years, a creatinine clearance level <50 ml/min, or a body mass index <18.5 kg/cm2.

Results

A total of 524 patients were included; of these, 112 (21.4%) were fragile. Mean age was 77 (range 74–80) years. A total of 104 (92.9%) fragile and 372 (90.3%) non-fragile patients spent two nights or less in hospital corresponding to a median hospital stay of 42 (Q1-Q3: 25–47) and 32 (Q1-Q3: 23–46) hours, respectively. The primary efficacy outcome occurred in one (0.9%) fragile and one (0.5%) non-fragile patient (absolute risk difference [ARD] +0.4%; 95% CI: −1.1%; +4.4%). Major bleeding occurred in three (2.7%) fragile and three (0.7%) non-fragile patients; ARD +2.0% (+0.3%; +6.9%). All-cause 3-month mortality was low in both groups (0.9% vs. 0.2%; ARD +0.7%, −0.7%; +4.7%).

Conclusion

Early discharge and home treatment of fragile patients with acute PE appears to be feasible and acceptably safe. The HoT-PE trial supports the notion that these patients should not be a priori excluded from early discharge, but caution is warranted due to a possibly higher risk of major bleeding on DOAC treatment.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by the German Federal Ministry of Education and Research (BMBF 01EO1503).
Serum lactate levels are an independent marker for complications in acute pulmonary embolism: from the PERT registry
Authors: Wasserstrum Y , Lotan D , Oren D , Sanalla S , Itelman E , Dekel S , Beigel R , Shlomo N , Matetzky S
Published: November 2020

Introduction

Serum lactate is a marker for the presence and severity of imbalances between tissue oxygen supply and demand. There are only scare data regarding the significance of arterial lactate in PE patients.

Purpose

We sought to explore the significance of venous serum lactate as a short- and long-term predictor of adverse outcomes.

Methods

We prospectively enrolled 570 patients with topographically-confirmed pulmonary embolism, hospitalized in our center during 2016–2019. Patient's data was collected using an electronic medical record and follow-up interviews via telephone. The combined end point of hemodynamic instability, shock, mechanical ventilation, or need for CPR was prospectively documented during hospitalization as well as 1-year mortality.

Results

The analysis included 461 consecutive patients with available clinical data including venous lactate. The median age was 69 years, and 262 (58%) were female. Median serum lactate levels were 21 mg/dL (IQR 16–31). The composite endpoint was documented in 92 patients (20%), and lactate levels above 21 mg/dl had a higher incidence of the composite end point (26% vs, 14%, p=0.002). Similar findings were seen when adding either the need for escalating therapy (44% vs. 24%, p<0.001), in-hospital mortality (31% vs. 16%, p=0.001) or 30-day mortality (27% vs. 21%, p<0.001) to the previous composite. One-year mortality was significantly higher in the higher lactate group (17% vs 5%, p<0.001), and a lactate level above 21 mg/dL was independently associated with 1-year mortality in a Cox-regression model adjusted for age, gender and a history of heart failure or malignancy, HR 2.5 (95% CI 1.7–3.9).

In subgroup analyses, lactate levels were associated with 1-year mortality regardless of age or gender. Similar predictive trends for 1-year mortality were seen in patients stratified by diabetes status, a current malignancy, PE risk and right-ventricle abnormalities (see figure).

Conclusions

Venous serum lactate levels are associated with a myriad of in-hospital adverse outcomes, as well as long-term mortality. In a 1-year follow-up, a higher lactate level was predictive of mortality across various subgroups, with higher hazard ratios seen specifically in lower-risk patients. Further studies are needed in order to evaluate the possible prognostic role of the change in serum lactate during PE management.

Elevated lactate and 1-year mortality

Funding Acknowledgement

Type of funding source: None
The prevalence and risk factors of high-altitude pulmonary hypertension among native Tibetans in Sichuan Province, China
Authors: Gou Q.L , Shi R.F , Zhang X , Meng Q.T , Li X.R , Rong X , Zhabu G.W
Published: November 2020

Background

High-altitude pulmonary hypertension (HAPH) remains a concern due to its high mortality, however, studies evaluating its prevalence and risk factors are lacking.

Objective

To determine the prevalence of HAPH and its correlated factors among the highlanders living at 3200 metres above sea level in Ganzi Tibetan Automous Prefecture, Sichuan Province, China.

Methods

This was a single-center cross-sectional study involved 1129 subjects (mean age 46.6±14 years, 39% men). Native Tibetans with HAPH were defined as mean pulmonary artery pressure >30mmHg achieved from transthoracic echocardiography.

Results

The crude prevalence of HAPH was 6.2%, and was more prevalent in men compared to women (8.6% vs 4.6%, P=0.005). The elder was more likely to develop HAPH (OR: 5.308, 95% CI: 2.562–10.993). Highlanders with HAPH had more severe metabolic abnormalities (including elevated blood pressure, blood glucose, blood lipids, BMI, etc. P value<0.05) and significantly increased hemoglobin level (P=0.001). On multivariate logistic regression analysis, independent risk factors for HAPH were metabolic syndrome (OR: 3.128, 95% CI: 1.110–8.818), age (>60 years vs <40 years) (OR: 2.924, 95% CI: 1.282–6.669), and decreased SpO2 (OR: 1.072 per 1-unit decrease; 95% CI: 1.010–1.136).

Conclusion

It could be concluded that HAPH was prevalent among 6.2% native Tibetans in Sichuan Province, China. Increasing age, metabolic syndrome and decreased SpO2 were independent predisposing factors for HAPH

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): This study was funded by one Science and Technology Pillar Programs in Sichuan Province (Grant no. 2017SZ0008).
Clinical significance of the periaortic adipose tissue inflammation in patients with abdominal aortic aneurysms
Authors: Yamaguchi M , Hoshino M , Nogami K , Ueno H , Misawa T , Sumino Y , Hada M , Kanaji Y , Sugiyama T , Yonetsu T , Kakuta T
Published: November 2020

Background

Recent studies have reported the association between periaortic adipose tissue volumes identified by multi-detector computed tomography (MDCT) and the periaortic adipose tissue inflammation (PATI) identified by positron emission tomography, which may suggest the link between perivascular inflammation and aortic dilation. However, clinical significance of the PATI identified by MDCT remains elusive in patients with asymptomatic abdominal aortic aneurysm (AAA).

Methods

A total of 77 patients with AAA (diameter >30mm) who underwent the initial and follow-up MDCT examinations were studied retrospectively. PATI was assessed by the crude analysis of the mean CT attenuation value (−190 to −30 Hounsfield units; higher values indicating inflammation). The AAA progression (AP) was defined as the growth of AAA diameter >5.0mm/year from the initial to follow-up. Univariate and multivariate logistic regression analysis were performed to determine the predictors for AP.

Results

AP was observed in 19 (24.7%) patient, the median initial AAA diameter was 38.9 (32.7–42.9) mm, and the median progression of AAA diameter was 3.1 (1.5–4.9) mm/year. The initial AAA diameter (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.05–1.28; p-value=0.001) and the initial PATI (OR: 1.12; 95% CI: 1.05–1.20; p-value=0.004) were independent predictors of AP. PATI of −71.08 at initial MDCT and the initial AAA diameter of 37.7mm were the best cut-off value to predict AP. Receiver operating characteristic curve analysis revealed that the best cut-off values of PATI at initial MDCT and the initial AAA diameter for predicting AP were −71.08 (AUC: 0.68, 95% CI: 0.50–0.82) and 37.7 (AUC: 0.71, 95% CI: 0.59–0.84), respectively. Addition of the initial AAA diameter to PATI at initial MDCT significantly increased the accuracy for discriminating AP (net reclassification improvement; 95% CI: 0.67 [0.17–1.17]; p-value = 0.007, integrated discrimination improvement; 95% CI: 0.14 [0.04–0.24]; p-value =0.007).

Conclusions

PATI was an independent and significant predictor of aortic dilation, supporting the notion that local adipose tissue inflammation may contribute to aortic remodeling. Comprehensive assessment of MDCT including PATI evaluation may provide a highly accurate information for identifying high risk lesions potentially leading to future AAA rupture.

Funding Acknowledgement

Type of funding source: None
The length of the fusion between leaflets in bicuspid aortic valve is independently related to ascending aorta dilation and flow dynamics alterations assessed by 4D-flow CMR
Authors: Guala A , Evangelista A , La Mura L , Teixido-Tura G , Dux-Santoy L , Ruiz-Munoz A , Cinque A , Valente F , Lopez Sainz A , Galian Gay L , Gutierrez L , Gonzalez Alujas T , Sao-Aviles A , Ferreira I , Rodriguez Palomares J.F
Published: November 2020

Background

Aortic dilation in bicuspid aortic valve (BAV) patients has been related to altered flow patterns, which contribute to aortic wall degeneration. However, preventive aortic replacement is currently based on a diameter threshold. Several studies on excised BAV reported wide variability of fusion extent.

Purpose

To unveil whether leaflet fusion extent can be quantified by CMR and is related to aortic dilation and flow abnormalities in non-dysfunctional BAV.

Methods

One hundred and twenty adults with non-dysfunctional BAV and no previous aortic or aortic valve surgery and 28 healthy volunteers underwent double-oblique cine and 4D flow CMR. BAV patients with two sinuses of Valsalva or left and non-coronary cusps fusion were excluded. Peak systolic circumferential wall shear stress (WSSc) and pulse wave velocity (PWV) in the ascending aorta (AAo) were assessed by 4D flow CMR. Fusion length between leaflets was measured using a stack of double-oblique cine CMR images of the aortic valve.

Results

The length of the fusion was effectively measured in 112/120 (93%) patients with good reproducibility (ICC = 0.826) and showed great variability (range 2.3–15.4 mm, 7.8±3.2 mm and tertiles cut-off points 6 and 9.3 mm). In multivariate analysis adjusted for clinical and demographic characteristics and PWV, fusion length was independently associated with the diameter at the sinus of Valsalva (p=0.002) and the AAo (p=0.02) (Table). WSSc progressively increased with larger fusion length (Figure), with statistical significance (p<0.05) in the right and outer regions of the proximal and mid AAo.

Conclusions

Bicuspid aortic leaflet fusion length varies considerably, and it is independently associated with AAo and aortic root dilation, possibly through flow alterations.

Figure 1. Maps of circumferential WSS

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study has been partially funded by Instituto Carlos III, Spanish Ministry of Science and Innovation (PI17/00381). Guala A. has received funding from the Spanish Ministry of Science, Innovation and Universities (IJC2018-037349-I).
Atlas of the immune cell repertoire in human atherosclerotic plaques characterized by single cell RNA-sequencing and multi-color flow cytometry
Authors: Horstmann H , Lindau A , Hansen S , Stachon P , Hilgendorf I , Bode C , Zirlik A , Wolf D
Published: November 2020

Rationale

Atherosclerosis is a chronic inflammatory disease that is driven by the accumulation of pro- and anti-inflammatory leukocytes in the intima of affected arteries. Yet, the cellular composition of human atherosclerotic plaques is only poorly understood. Here, we characterized immune cells to human carotid atherosclerotic plaques by multi-color flow cytometry and scRNAseq.

Methods and results

First, we compared a set of previously reported digestion protocols to liberate leukocytes from human carotid plaques after surgical thrombendarteriectomy. One digestion cocktail, containing Collagenase IV and DNase I, was superior regarding cell survival and cell surface marker preservation. Second, leukocytes from 56 surgical specimen were characterized by flow cytometry with a set of 16 parameters and cell surface markers capable of identifying principal hematopoietic leukocyte lineages. This protocol allowed to extract and analyze on average 4x103 viable CD45+ leukocytes from a mean of 988 mg plaque tissue. Surprisingly, we found that atherosclerotic plaques were dominated by T cells with 33.7±2.2% CD4+ T-helper cells and 25.6±2.5% CD8+ cytotoxic T cells. CD11b+ myeloid cells, including monocytes and macrophages, represented only 20.2±4.0% of all CD45+ leukocytes. CD19+B cells and CD56+ NK-cells accounted for 3.9±1.2 and 3.3±0.5%, respectively. TCR-g/d+ T cells and neutrophils were undetectable in atherosclerotic plaques. This cellular composition differed significantly from peripheral blood, but was not relevantly changed between different plaque locations, indicating that macrophage-rich necrotic cores mostly contain dead cells. We confirmed the principal composition of human plaques by single-cell RNA-sequencing from six patients. To allow an estimation of cellular heterogeneity independent of classical cell surface marker assignment, we performed an unsupervised cluster detection algorithm by t-distributed stochastic neighbor embedding (tSNE) and found more than 16 leukocyte clusters with unique cell surface marker expression, suggesting an unexpected high diversity of plaque leukocytes.

Conclusion

We developed an immune cell phenotyping protocol optimized for human carotid plaques. The definition of phenotypes and frequencies in atherosclerotic plaques will allow to build clinical associations between the immune cell composition and clinical outcomes in future.

Funding Acknowledgement

Type of funding source: None
Microvascular disease, peripheral artery disease, and the risk of lower limb amputation
Authors: Olesen K.K.W , Anand S.S , Gyldenkerne C , Thim T , Maeng M
Published: November 2020

Background

Peripheral artery disease (PAD) is the leading cause of non-traumatic lower limb amputation. Microvascular disease (peripheral neuropathy, nephropathy, or retinopathy) increases the risk of lower limb amputation in patients with established PAD.

Purpose

We estimated risk of lower limb amputation associated with microvascular disease and PAD in a Danish cohort.

Methods

We conducted a population-based cohort study of every person living in Western Denmark aged 50–75 years on January 1, 2012 and followed them for 7 years. People with previous lower limb amputation were excluded. People were stratified by the presence of microvascular disease (peripheral neuropathy, nephropathy, or retinopathy) and PAD (peripheral atherosclerosis including intermittent claudication, or previous lower limb revascularization). We estimated the 7-year cumulative incidence and hazard ratio (HR) of lower limb amputation using individuals with neither microvascular disease nor PAD as reference. We also provide a sex-specific analyses and estimated the population attributable fraction of amputation associated with male sex.

Results

We included 933,597 individuals, of whom 16,007 had microvascular disease, 18,400 had PAD, and 1,789 had both microvascular disease and PAD. Patients with either microvascular disease (3.7%) or PAD (3.9%) had similar unadjusted 7-year risks of lower limb amputation (Figure). Microvascular disease (adjusted HR 3.21, 95% CI 2.86–3.59) and PAD (adjusted HR 7.37, 95% CI 6.68–8.14) increased the risk of lower limb amputation separately in adjusted analysis. Individuals with both microvascular disease and PAD had the highest risk of amputation (adjusted HR 11.82, 95% CI 10.11–13.80). While the relative impact of microvascular disease and PAD were similar in men and women, men had increased risk of amputation compared to women, in absolute terms. The population attributable fraction of amputations associated with male sex was 31%.

Conclusion

Microvascular disease and PAD are independently associated with a 3-fold and 7-fold increase of amputation rate, respectively. Combined, microvascular disease and PAD had an additive effect constituting a 12-fold amputation risk. Amputation risk was higher in men than in women, with 3 in 10 lower limb amputations in Western Denmark attributable to male sex.

Figure 1

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Department of Cardiology, Aarhus University Hospital
Clinical impact of peripheral artery disease on acute coronary syndrome
Authors: Fonseca Goncalves F , Borges S.C , Monteiro J.J , Mateus P.S , Moreira J.I
Published: November 2020

Introduction

Peripheral artery disease (PAD) and acute coronary syndrome (ACS) are two diseases with high morbidity and mortality and, sometimes, may be present simultaneously, making patient management more complex.

Purpose

This study sought to characterize and evaluate the prognostic impact of PAD in patients with an ACS.

Methods

This was a retrospective study of patients admitted with an ACS, periodically included in a national multicenter registry, between October 2010 and September 2019.

Results

Of a total of 26036 patients, 1429 had previous history of PAD. This group had a higher predominance of men (79,5% vs 72,0%, p<0,001) and was older (71±11 years vs 66±14 years, p<0,001). Besides having a higher burden of cardiovascular risk factors, they also had more past history of myocardial infarction (MI), stroke and chronic kidney disease.

In patients with PAD, non-ST segment elevation MI was the most frequent type of MI (58,6% vs 45,0%, p<0,001) and left ventricular ejection fraction assessed during hospitalization was lower (49±13% vs 51±12%, p<0,001). These patients were submitted less frequently to a coronary angiography (74,0% vs 85,2%, p<0,001) and, when performed, more cases of multivessel coronary artery disease were found (70,6% vs 50,4%, p<0,001). Nevertheless, they were less likely to undergo revascularization, with fewer angioplasties performed (47,8% vs 64,7%, p<0,001), despite the greater number of coronary artery bypass grafting (9,0% vs 6,0%, p<0,001). Both during hospitalization and at discharge, ticagrelor, beta-blockers and ACE inhibitors were less prescribed in the PAD group. Statins prescription was also lower, but only at discharge.

In a multivariate regression analysis, we found that, during hospitalization, the presence of PAD was associated with a significant higher risk of myocardial reinfarction (OR 1,90 (CI 1,18–3,06)) and death (OR 1,43 (CI 1,03–2,00)). In addition, there was a tendency for more strokes (OR 1,88 (CI 0,98–3,61)). During a 1-year follow-up, PAD was also independently associated with a significant increase in mortality (HR 1,50 (CI 1,16–1,95)).

Conclusions

PAD is a disease present in patients with a higher number of comorbidities and is associated with more severe coronary events. Nevertheless, these patients seem to receive less evidence-based therapy. In this study, PAD was independently associated with a significant increase in short and medium-term major adverse events.

Kaplan-Meier curves of 1-year follow-up

Funding Acknowledgement

Type of funding source: None
History of stroke is a major factor to affect prognosis of elderly chronic limb-threatening ischemia patients with frailty after endovascular therapy
Authors: Kanda D , Ikeda Y , Sonoda T , Anzaki K , Arikawa R , Tokushige A , Ohishi M
Published: November 2020

Background

Chronic limb-threatening ischemia (CLTI) is the most advanced form of severe arteriosclerosis, and CLTI patients are known to have poor prognosis due to complication of polyvascular diseases, including cerebrovascular disease. Stroke often causes disability of exercise, leading to develop frailty and sarcopenia, and frailty and sarcopenia are known to important factors affecting the prognosis of cardiovascular disease. However, the effect of history of stroke for clinical outcomes in elderly CLTI patients with frailty has not been well evaluated.

Purpose

The aim of the present study was to investigate whether a history of stroke affects prognosis of elderly CLTI patients with frailty after endovascular therapy (EVT).

Methods

The subject was 228 consecutive elderly (≥65 year) CLTI patients underwent EVT. These patients had frailty with clinical frailty scale 5 or 6 or 7 which was defined by Geriatric Medicine Research. Clinical frailty was assessed on admission before procedure of EVT by physicians or other health professionals. The study patients were divided into two groups based on patients with or without history of stroke group (Group A and B). We investigated the association between history of stroke on admission and outcome after EVT.

Results

All-cause death ≤6 month and ≤12 month after EVT were 10 cases (4%) and 19 cases (8%). Group A had higher rate of all-cause death ≤6month and ≤12 month (14 vs. 3%, p=0.012, 19 vs. 6%, p=0.019) than those of Group B. Kaplan Meier analysis elucidated that survival rate was significantly lower in Group A compared to that in Group B (p=0.031). As a result of cox proportional hazards analysis, all-cause death ≤6 month was associated with history of stroke [hazard ratio (HR): 5.07, 95% confidence interval (CI): 1.47–17.52, p=0.010)], hs-CRP (HR: 1.09, 95% CI: 1.01–1.16, p=0.010) in the univariate analysis. Similarly, cox proportional hazards analysis for revealed that history of stroke (HR: 3.02, 95% CI: 1.19–7.68, p=0.020), hs-CRP (HR: 1.09, 95% CI: 1.03–1.14, p<0.001), hemodialysis (HR: 2.53, 95% CI: 1.03–6.24, p=0.043), use of clopidogrel (HR: 0.22, 95% CI: 0.07–0.78, p=0.019) and serum albumin level (HR: 0.40, 95% CI: 0.21–0.80, p=0.008) were significantly associated with all-cause death ≤12 month. Multivariate analysis models after adjusted for the demographic characteristics of patients and clinically relevant factors for all-cause death ≤6 month and ≤12 month after EVT revealed that history of stroke was an independent risk factor (HR: 5.18, 95% CI: 1.44–17.43, p=0.011, HR: 2.98, 95% CI: 1.71–7.61, p=0.022).

Conclusions

These data suggested that history of stroke was a crucial independent predictor for incidence of all-cause death in elderly CLTI patients with frailty.

Funding Acknowledgement

Type of funding source: None
Can left atrial mechanics predict anticoagulation in cryptogenic stroke?
Authors: Azul Freitas A , Milner J , Ferreira J , Ferreira C , Martinho S , Almeida J , Goncalves V , Jorge E , Goncalves L
Published: November 2020

Introduction

Ischemic stroke is a leading cause of death and disability in the Western world, frequently due to cardioembolism and atherothromboembolism. Cryptogenic strokes occur without a well-defined aetiology after a standard vascular and cardiac evaluation, and secondary prevention may include antiplatelet therapy while awaiting results of long-term cardiac monitoring. In this study, we aimed to identify echocardiographic predictors of paroxysmal atrial fibrillation (AF) latter identified in follow-up of patients with cryptogenic stroke.

Methods

We retrospectively assessed all patients with cryptogenic stroke admitted in our hospital in the last 2 years. Only patients in normal sinus rhythm with a minimum of 24 hours of cardiac monitoring at admission and 24 hours Holter monitor within 6 months after discharge were included. Echocardiographic measures included left ventricle ejection fraction, left atrium (LA) volume, left and right atrium longitudinal strain, left and right ventricle longitudinal strain, E/A ratio, E/e' ratio, isovolumetric relaxation time (IVRT) and E wave deacceleration time. Echocardiographic data was assessed to determine its accuracy to identify AF.

Results

The study included 32 patients with a mean age of 72±10 years and a male preponderance (87.5%). AF was identified in 12 (37.5%) patients. This group of patients had a larger indexed LA volume (44.3 vs 29.1 mL/m2, p=0.043), a lower IVRT (87 vs 116 ms, p=0.028), and a lower LA longitudinal strain in contractile (6.7 vs 13.6%, p<0.001) and in reservoir phase (17.1 vs 23.6%, p=0.042). All other variables were not significantly different among groups, including LA longitudinal strain in conduit phase. LA longitudinal strain in contractile phase showed the best predictive power with an area under the ROC curve of 0.925 (95% CI 0.82–1 p=0.001). The cut-off value that best predicted AF was 8.17% with a sensitivity of 1 and specificity of 0.9.

Conclusion

LA longitudinal strain in contractile phase is a powerful method to identify AF in cryptogenic stroke. When reduced, anticoagulation may be considered in order to prevent recurrence. Further studies are warranted to reproduce these results in larger cohorts.

Funding Acknowledgement

Type of funding source: None
Different clinical features between left atrial and left atrial appendage thrombus: an insight into more than 16,000 transesophageal echography database
Authors: Fukunaga M , Masuda H , Isotani A , Morinaga T , Yano M , Miura S , Ando K
Published: November 2020

Background

Thrombosis localization inside the left atrium (LA) is very frequently in the left atrial appendage (LAA). Some cases show atrial thrombus outside LAA, whose characteristics have not well elucidated.

Purpose

To reveal the different clinical background between thrombus inside LAA and outside LAA in a large transesophageal echo (TEE) database.

Methods

We searched the TEE database over 8 years of our center to identify patients in whom LA thrombus was pointed out. After initial TEE imaging, LA thrombus was confirmed with repeated TEE by echocardiography specialist or other modality, such as CT images.

Results

In a consecutive 16,142 TEE cases, LA thrombus was suspected in 162 cases (1%), finally 38 cases were identified as LA thrombus. They were divided into two groups; LAA only group and outside LAA group. Atrial fibrillation was concomitant in 34 patients (89%). History of stroke was significantly higher in LAA group (46.2% vs 8.3%, p=0.03) and malignant tumor was significantly higher in outside LAA group (23.1% vs 58.3%, p=0.035). LA thrombus was the first symptom in 3 cases of outside LAA group, following by malignant tumor was newly detected. Oral anticoagulation was prescribed in 23 cases (61%) at TEE study, mostly treated with warfarin, and median 123 days later thrombus dissolution was confirmed in 21 cases (55%). During mean follow up of 893 days, 4 patients experienced ischemic stroke, but two of them were due to self-interruption.

Conclusion

Outside LAA thrombus is minor but more concomitant with malignant tumor. Physician must be aware that screening of cancer is important if outside LAA thrombus is detected.

Funding Acknowledgement

Type of funding source: None
Statin use associated with lower mortality in very elderly patients with peripheral arterial disease
Authors: Tseng A , Girardo M , Liedl D , Bhatt S , Wennberg P , Shamoun F
Published: November 2020

Introduction

Given the potential side effects and the lack of data on its efficacy, the role of statins in the very elderly (age 75+) with peripheral arterial disease (PAD) is uncertain. Previous studies have shown significant mortality benefit in very elderly patients with coronary artery disease, but the effect in PAD has not been evaluated.

Methods

Very elderly patients aged 75 to 80 with at least five years of follow-up who underwent ankle-brachial index (ABI) measurement were included. PAD was defined as either low ABI <0.90 or high ABI >1.40. Demographic, medication use, comorbidity and mortality data was obtained using the electronic medical record. Univariate and multivariate Cox proportional hazard analyses were performed.

Results

In total, 4,560 very elderly subjects with PAD were included in the analysis. The median age was 77 (interquartile range 76–79) and 39% were female. 3,462 (76%) had low ABI while 1098 (24%) had high ABI. Univariate analysis showed that patients on statins were more likely to be male, have diabetes, have coronary artery disease, and have hyperlipidemia. Overall, 1,355 (30%) patients died in the five-year period. Unadjusted all-cause mortality hazard ratios for patients with low or high ABI with statin use was 0.66 (95% confidence interval [CI]: 0.57–0.75) and 0.80 (95% CI: 0.66–0.97), respectively. After adjusting for age, sex, coronary artery disease and diabetes, statin use in low and high ABI was still associated with significant reductions in risk of all-cause mortality of 0.59 (95% CI: 0.51–0.67) and 0.66 (95% CI: 0.54–0.80), respectively. The survival curve for very elderly patients with PAD by statin use is shown in Figure 1.

Conclusion

Statin use in the very elderly was associated with lower risk of all-cause mortality in the five-year period after diagnosis of PAD. There appears to be a mortality benefit with statin use in the very elderly with PAD, though careful consideration of benefits and side effects should be individualized in this age group.

Figure 1

Funding Acknowledgement

Type of funding source: None
Clinical benefits of the orthogonal tri-axial technique in the left atrial appendage closure procedures
Authors: Du X.F , Chu H.M , Fu G.H , Wang B.H
Published: November 2020

Background

Intracardiac echocardiography (ICE) has been an alternative imaging guidance of transesophageal echocardiography (TEE) in the left atrial appendage closure (LAAC) procedures. However, its application experience is limited.

Objective

We aimed to analyze the clinical benefits of an orthogonal tri-axial (OTA) technique using ICE and electroanatomic mapping system (EAMS) in the LAAC procedures.

Methods

This retrospective study enrolled 52 atrial fibrillation (AF) patients with high risks of stroke and/or bleeding (CHA2DS2-VASc score 4.67±1.48; HAS-BLED score 2.87±0.94) who underwent the LAAC procedures following the OTA technique (ICE group). ICE probe was advanced into left atrium (LA) navigated by the EAMS. Evaluation of sizing and device implantation were performed from three orthogonal axes including axis-X: from left pulmonary veins (PVs) to LAA; axis-Y: from right PV ostium to LAA; axis-Z: from lower LA to LAA. Procedure-related parameters and clinical outcomes were compared to those from another 52 patients with comparable baseline characteristics who underwent LAAC following the TEE guidance (TEE group). All procedures were achieved under local anesthesia.

Results

The fluoroscopic exposure (99.5±113.6 vs 229.0±135.4mGy, P<0.001) and time (5.9±4.7 vs 8.1±3.9min, P=0.011) and contrast consumption (66.5±54.9 vs 124.1±69.6ml, P<0.001) in the ICE group were significantly lower than those in the TEE group, respectively, without increasing the procedural time (79.6±24.4 vs 82.3±39.5min, P=0.674). Similar proportions of Watchman (26 vs 32, P=0.236) and ACP (10 vs 13, P=0.478) devices were recorded between groups while more LAmbre devices were applied in the ICE group (16 vs 7, P=0.033). All procedures were accomplished successfully. The fluoroscopic exposure (22.9±32.7 vs 228.9±148.6mGy, P<0.001) and time (1.9±2.9 vs 9.9±5.0min, P<0.001), the contrast consumption (17.7±21.7 vs 124.6±62.8ml, P<0.001) and the procedural duration (74.6±19.7 vs 88.1±20.6min, P=0.107) were lower in the last 25% cases in the ICE group compared to the first 25% cases. Both acute and long-term (during the 45-day and 6-month follow-ups) peri-device leaks (PDLs) were similar between groups. No procedure-related complications or thromboembolism events were observed.

Conclusions

The advantage of the ICE- plus EAMS-guided LAAC in fluoroscopic exposure and contrast consumption minimizing could be expected following the OTA technique. Procedural efficiency improves after the learning curve.

Funding Acknowledgement

Type of funding source: None
Biomarkers in patients with cryptogenic stroke/TIA and subclinical atrial fibrillation
Authors: Kjekshus H , Skrebelyte-Strom L , Bakkelund V , Arnesen H , Ronning O.M , Steine K , Seljeflot I
Published: November 2020

Background

A large proportion of patients with cryptogenic stroke or transitory ischemic attack (TIA) have underlying subclinical atrial fibrillation (SCAF) detected on follow up. It is not clear whether SCAF is the underlying primary entity in the pathogenesis of stroke in these patients, or merely a marker of atrial myopathy associated with left atrial remodeling, fibrosis and inflammation.

Purpose

As a hypothesis generating study, we investigated a panel of selected biomarkers involved in fibrosis, inflammation, and thrombosis: growth differentiation factor 15 (GDF-15), transforming growth factor b (TGFb), galectin-3, soluble suppressor of tumorgenicity2 (sST2), von Willebrand factor (vWF), Tissue metalloprotease1 (TIMP1), Matrix metalloprotease9 (MMP9), Emmprin, Interleukin6 (IL6), C-reactive protein (CRP), Tissue factor (TF), Plasminogen activator inhibitor (PAI1), and their relation to the occurrence of SCAF during follow-up in patients after cryptogenic stroke or TIA. We hypothized that biomarker levels were increased in patients with subclinical AF.

Methods

236 patients, median age 71 years (range 21–94) of which 38% were women, with their first cryptogenic stroke or TIA were included 2–4 days after the index event and followed with an Implantable Cardiac Rhythm Monitor for >1 year. Echocardiography and blood sampling were performed at inclusion. ELISA methods were used.

Results

SCAF occurred in 84 patients (36%). Only GDF-15 was significantly increased in AF- vs no-AF patients: 1010 pg/mL (inter quartile range: 814–1416) vs 860 pg/mL (inter quartile range: 622–1197) (p=0.018), and correlated with the number of premature atrial contractions (PAC)/24h (by Holter ECG during index hospitalization) (rs=0.314, p<0.001) and AF-burden during follow-up (rs=0.149, p=0.022). Furthermore, there was a significant trend across quartiles of GDF-15 for having AF, and patients in the three highest quartiles (Q2–4) compared with Q1 had an odd ratio of having AF of 2.16 (95% CI 1.10–4.25), adjusted for sex and body mass index. The significance, however, was lost when adjusting for age, which correlated significantly to GDF-15 (rs=0.283; p<0.001). ROC curve analyses showed an AUC of 0.593 (0.52–0.68) for GDF-15 compared to 0.617 (0.54–0.69) for age. GDF-15 was also associated with co-morbidities such as hypertension (p<0.001), diabetes (p<0.001), and vascular disease (p<0.001).

Conclusion

In patients with a cryptogenic stroke or TIA experiencing SCAF during follow up, only levels of GDF-15 were elevated and correlated with PAC/24h and AF-burden. However, GDF-15 was highly related to age and co-morbidities and did not add significantly to the prediction of AF in a multivariate analysis.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Stiftelsen Dam, Norwegian Atrial Fibrillation Research Network
Clinical profile and predictors of positivity of acetylcholine test in patients with angina and no obstructive coronary artery disease. Results of a multi-center mediterranean registry
Authors: Grigorian L , Gutierrez E , Oteo J.F , Abdul-Jawad O , Amat Santos I , Gutierrez Barrios A , Fernandez Cisnal A , Jimenez Mazuecos J , Roa J , Vazquez M.E , Sanz R , Diez-Delhoyo F , Rivera A , Elizaga J , Fernandez-Aviles F
Published: November 2020

Background

Coronary endothelial dysfunction and vasospasm are potential causes of ischemia in no obstructive coronary disease (INOCA) and are now known to be associated with an increased risk of major cardiovascular events (MACE) and impaired quality of life. The recent guidelines recommend the use of intracoronary acetylcholine to unravel the underlying pathophysiology of INOCA, by identifying those with endothelial dysfunction, and to guide future treatment in these patients.

Objective

To evaluate the clinical profile and prevalence of endothelial dysfunction in patients with INOCA, and to identify the predictors of positivity of the acetylcholine test.

Methods

A total of 358 patients with INOCA were prospectively enrolled in a multicenter observational study. Coronary angiography and acetylcholine test were performed according to clinical indications in all included patients. Patients were followed-up for 1-year for MACE and clinical reevaluation of symptoms.

Results

Patients' mean age was 60.6±13.5 y.o. and 58.7% were females, with no previous history of coronary heart disease in 76% of cases. Regarding clinical presentation, 56.9% had angina at rest, 59.9% exertional angina, and 29.5% dyspnea. In 39% the EKG was abnormal, and in 10.9% there was a troponin rise.

Coronary endothelial dysfunction –defined as a vasoconstriction over 30%– was observed in 129 (36%) patients, and severe vasoconstriction (>70%) in 75 (21%). Of positive cases, 47 (36%) focal vasoconstriction, and 90 (70%) diffuse. On follow-up, patients with a positive Ach test were treated differently, with a lower prescription of betablockers (12% vs. 24%, p=0.01) and a higher use of vasodilators (47% vs. 28.5%, p=0.001). Guidelines-recommended optimal treatment was prescribed to 39.2% of patients with a positive acetylcholine test. Patients with positive acetylcholine test were more prone to having worsening angina (25.6% vs. 12.8%, p<0.01) and minimal exertion angina (40% vs. 26.7%, p=0.03) on follow-up. Multivariable regression analysis showed that acetylcholine test positivity was predicted by the presence of diabetes (OR 1.7, p=0.04), exertional angina (OR 1.2, p=0.04), coronary atherosclerosis (OR 1.8, p=0.02) and coronary milking (OR 2.6, p=0.04).

Conclusions

Endothelial dysfunction detected by acetylcholine test was present in one third of patients with INOCA and was associated with more severe and worsening symptoms. Although Ach test positivity influenced the pharmacological treatment at discharge, a large room for optimization still remained.

Funding Acknowledgement

Type of funding source: None
Circadian variations in pathogenesis of ST-segment elevation myocardial infarction
Authors: Araki M , Yonetsu T , Kurihara O , Nakajima A , Lee H , Soeda T , Minami Y , Yan B.P , Adriaenssens T , Boeder N.F , Nef H.M , Kim C.J , Crea F , Kakuta T , Jang I.K
Published: November 2020

Background

Previous studies have reported a circadian variation in the onset of ST-segment elevation myocardial infarction (STEMI). However, underlying mechanisms for the circadian variation have not been fully elucidated.

Purpose

We investigated the relationship between onset of STEMI and the underlying pathology using optical coherence tomography (OCT).

Methods

Patients presenting with STEMI were selected from an international, multi-center, longitudinal registry study, which included patients who underwent OCT imaging of the culprit lesion at 11 institutions in 6 countries. Onset of MI was estimated using the time of OCT imaging. Patients were divided into 4 groups based on the estimated time of onset (00:00–05:59, 06:00–11:59, 12:00–17:59, or 18:00–23:59). Underlying pathologies of MI (plaque rupture, plaque erosion, and calcified plaque) were compared among the 4 groups.

Results

Among 648 patients, plaque rupture was diagnosed in 386 patients (59.6%), plaque erosion in 197 patients (30.4%), and calcified plaque in 65 patients (10.0%). A marked circadian variation was detected in the incidence of plaque rupture with a peak at 9:00, whereas it was not evident in plaque erosion or calcified plaque. The probability of plaque rupture increased in the periods of 06:00–11:59 (odds ratio: 2.13, 95% confidence interval: 1.30 to 3.49, p=0.002) and 12:00–17:59 (odds ratio: 2.10, 95% confidence interval: 1.23 to 3.58, p=0.005), compared to the period of 00:00–05:59. This circadian pattern was observed only during weekdays (p=0.013) and it was not evident during the weekend (p=0.742).

Conclusions

Plaque rupture occurred most frequently in the morning and the circadian variation was evident only during the weekdays. Acute MI caused by plaque rupture may be related to catecholamine surge.

Funding Acknowledgement

Type of funding source: None
Comparison of iFR and FFR for coronary physiology evaluation in patients with severe aortic stenosis
Authors: Kleczynski P , Dziewierz A , Rzeszutko L , Dudek D , Legutko J
Published: November 2020

Background

Reliable coronary physiology assessment with pressure derived indexes in patients with aortic stenosis (AS) rises problems due to its complex nature. Recent data suggest that fractional flow reserve (FFR) may underestimate intermediate coronary stenosis in a presence of AS whereas instantaneous wave-free ratio (iFR) values may remain similar after treatment of AS. Furthermore, both indices has not been validated yet in AS.

Aim

We aimed to find a thresholds for coronary ischemia in the setting of aortic

Material and methods

The functional significance of 416 coronary lesions was investigated with iFR and FFR measurements in 221 AS patients. The iFR-FFR diagnostic agreement has been tested using the cut-off value for iFR of 0.89.

Results

Mean value of %DS was 58.6±13.4%, FFR was 0.85±0.07 and iFR – 0.90±0.04. FFR ≤0.80 was measured in 26.0% of interrogated vessels, iFR ≤0.89 – in 33.2%. The correlation between iFR and FFR was good (r=0.83, p<0.001) and with good agreement between iFR and FFR (mean difference −0.0059, 95% CI −0.056–0.062). The AUC at ROC curve analysis for iFR ≤0.89 was 0,997 (0,986 to 1,000, p<0.001) for FFR. According to ROC analysis, the best FFR cut-off in predicting iFR ≤0.89 was ≤0.82 (J=0.96). The diagnostic accuracy for identifying iFR ≤0.89 was 97.7% for FFR.

Conclusion

In the presence of AS, FFR had good agreement with iFR values. However, FFR threshold for predicting iFR below 0.89 may be different from a standard threshold and that should be taken into account while assessing coronary physiology in the setting of AS.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Science Center
Comparison of fractional flow reserve and instantaneous wave-free ratio for the hemodynamic assessment of jailed side branches in bifurcation stenting
Authors: Altstidl J.M , Marwan M , Troebs M , Achenbach S , Gaede L
Published: November 2020

Background

Provisional side-branch stenting strategy is one of the preferred strategies for treatment of bifurcation lesions. Whereas using fraction flow reserve (FFR) for the physiologic assessment of jailed side branches is well studied, the reliability of resting indices such as instantaneous wave free ratio (iFR) is unknown.

Methods

Consecutive patients with provisional stenting of a bifurcation and a jailed side branch were enrolled in this study. FFR and iFR were measured and, after assuring absence of baseline shift and drift, both measurements were repeated after 3 minutes. Hyperemia was induced by intra-coronary adenosine with a dose of 48μg for the right coronary artery and 96μg for the left coronary artery. Cut-off for the assumed functional significance of a stenosis was 0.80 for FFR and 0.89 for iFR. The decision to treat the side branch was left to the interventionalist's discretion.

Results

37 jailed side branches in 36 patients (age 68.4±8.2; male 81% (n=29)) were consecutively enrolled in the study. The main vessel was the left main in 3% (n=1), the left anterior descending (LAD) in 65% (n=24), the diagonal branch (D1) in 3% (n=1), the left circumflex artery (LCX) in 24% (n=9) and the right coronary artery (RCA) in 5% (n=2). The Medina classification revealed true bifurcation stenosis defined as Medina 1–1-1 prior to treatment in 35% (n=13).

FFR showed 35% (n=13) of the stenosis to be functionally significant with a high reproducibility of the results (r=0.986). FFR showed a low correlation with angiographic assessment (r=−0.477). iFR indicated hemodynamic relevance in 38% of lesions (n=14) with a high reproducibility (r=0.967) and also correlated poorly with angiographic assessment (r=−0.271). iFR was found to closely correlate with FFR in jailed side branches (r=0.720, Figure 1A). Bland-Altman analysis showed iFR and FFR agreed with a mean difference between FFR and iFR of −0.054±0.146. In 81% (n=30) FFR and iFR showed the same results regarding functional significance. In 8% (n=3) FFR was ≤0.80 and iFR >0.89, in 11% (n=4) FFR was >0.80 and iFR was ≤0.89 (Figure 1B).

Side branch treatment was performed in 32% (n=12). All of these lesions showed functional significance in FFR or iFR. Stent implantation was performed in 8% (n=3), balloon angioplasty in 19% (n=7) and balloon angioplasty with a drug-eluting balloon in 5% (n=2).

Conclusions

The results of this study confirm the poor correlation of angiographic and functional assessment of coronary artery stenoses. Our data show close agreement of iFR and FFR in stent-jailed side branches. Therefore, iFR can be considered as a reliable technique for guidance of provisional side branch stenting.

Figure 1

Funding Acknowledgement

Type of funding source: None
Predictors of intra-procedural stent thrombosis (IPST) during percutaneous coronary intervention (PCI): a pooled data analysis
Authors: Aggarwal A , Jain A , Beriwal N
Published: November 2020

Background

Among all PCI related intraprocedural thrombotic events, IPST is rare but associated with worst outcomes.

Purpose

We conducted this study to identify specific patient and procedural characteristics that are associated with higher incidence of IPST.

Methods

Data on patient and procedural characteristics from all the studies comparing IPST without IPST was pooled for the purpose of analysis.

Results

5 studies with a total of 21251 patients were included. IPST occurred in 170 patients (0.8%). History of a prior PCI (assumed to be on dual or single anti-platelet agent)was associated with decrease in IPST. IPST occurred more in smokers, patients with abnormal cardiac enzymes at presentation, presentation with STEMI. Incidence of IPST was significantly higher in interventions involving left main artery or bifurcation or with bare metal stent placement. A low pre-TIMI flow of 0 or 1, baseline thrombus, not using upstream GpIIb inhibitors also significantly increased incidence of IPST.

Conclusion

Further studies are needed to validate above described patient and procedural risk factors. Using upstream GpIIb inhibitors in this specific high-risk population may help in prevention.

Funding Acknowledgement

Type of funding source: None