bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic relevance of sleep apnea syndrome in patients with pulmonary arterial hypertension
Authors: Precek J , Vykoupil K , Kovacik F , Hutyra M
Published: November 2020

Introduction

Sleep disordered breathing (SDB) is a group of ventilatory disorders during sleep which includes obstructive sleep apnea (OSA), central sleep apnea (CSA), and sleep related hypoventilation. In patients with SDB, the prevalence of pulmonary hypertension (PH) ranges from 17% to 52%. While SDB is prevalent in the general population with recent estimates of 20% to 30%, in those with cardiovascular disease, particularly left ventricular failure, there is a higher reported prevalence of 47%.

Aims

The aims of this study were to determine the prevalence and prognostic relevance of sleep apnea in a cohort of patients with newly diagnosed pulmonary arterial hypertension (ESC/WHO Group 1 pulmonary hypertension).

Methods

We evaluated prospectively 76 patients with the pulmonary arterial hypertension (mean age 54±16 years; 45% male). All patients underwent right heart catheterisation, clinical assessments, sleep study, standard laboratory testing and evaluation of subjective sleepiness by the Epworth Sleepiness Scale. Sleep test was provided with an ApneaLink Plus, consisting of nasal pressure sensor, respiratory effort band, and pulse oximeter worn on the finger. Subjects previously treated for or diagnosed with SDB were excluded from the study.

Results

Sleep apnea (SA) – defined as apnea-hypopnea index (AHI) ≥5/h – was found in 59 (77.6%) of the pulmonary arterial hypertension (PAH) patients. Mean AHI in the cohort of PAH patients with SA was 26.1±16.6/h. Mean follow-up was 24 months, during which 15 (19.7%) patients died. Characteristics of parameters related to SA in groups of survivors and deceased are in table 1. From the sleep apnea-related parameters, only time with O2Sat <90% – T90 was significantly associated with mortality (AUC 0.856; 95% CI 0.693 – 1.019; p<0.001).

Conclusions

The presence of sleep apnea in pulmonary arterial hypertension patients is high. The prevalence of sleep apnea is higher in PAH patients than in the general population. The presence of sleep apnea in patients with PAH was not associated with worse prognosis, but noctural hypoxemia (time with O2Sat <90%) was related to poor prognosis. Sleep apnea in patients with PAH should be screened for systematically.

Funding Acknowledgement

Type of funding source: None
Microvasculopathy evaluated by dual-energy computed tomography in chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension
Authors: Miwa K , Taniguchi Y , Sumimoto K , Matsuoka Y , Izawa Y , Onishi H , Tsuboi Y , Toba T , Kobayashi S , Emoto N , Hirata K
Published: November 2020

Background

It has been previously reported that poor subpleural perfusion (PSP) in dual-energy computed tomography (DE-CT) might suggest the microvasculopathy in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, it remains unclear whether pathological findings of microvasculopathy in CTEPH and pulmonary arterial hypertension (PAH) are equivalent. The aim is to evaluate the microvasculopathy in CTEPH and PAH by using clinical parameters and DE-CT.

Methods

We retrospectively reviewed PSP (defined as subpleural spaces either not or minimally perfused in all segments) of consecutive treatment-naïve 89 CTEPH patients and 20 PAH patients who underwent DECT from Feb. 2015 to Dec. 2019.

We also evaluated hemodynamic parameters and DE-CT parameters including quantitative evaluation of pulmonary blood volume (PBV) which was calculated as the average of entire lung iodine density.

Results

PSP was observed in 49.4% of patients in CTEPH group versus 5.0% in PAH group (p<0.01).

There were no significant differences in hemodynamics and lung PBV between CTEPH group and PAH group (mean pulmonary arterial pressure; 36.4±10.4mmHg vs 38.3±8.5mmHg p=0.464, pulmonary vascular resistance; 700±388dyne*sec/cm5 vs 805±440 dyne*sec/cm5 p=0.288, lung PBV; 24.9±6.4 Hounsfield Unit vs 22.0±6.6 Hounsfield Unit p=0.06, respectively), however diffusing capacity for carbon monoxide (%DLCO/VA) was significantly lower (69.5±16.8% vs 45.7±23.7% p<0.01) in PAH group.

Conclusion

PSP in DE-CT, which was observed more frequently in patients with CTEPH, might suggest the different mechanism of microvasculopathy from PAH in patients with CTEPH. Microvasculopathy in CTEPH would be diffuse very distal thrombosis. DE-CT is effective modality to detect microvasculopathy of diffuse distal thrombosis in patients with CTEPH.

DECT, Poor subpleural perfusion

Funding Acknowledgement

Type of funding source: None
Cardiopulmonary exercise test could predict residual pulmonary hypertension after pulmonary endarterectomy
Authors: Coronel M.L , Flox Camacho A , Segura De La Cal T , Perez Olivares Delgado C , Cristo Ropero M.J , Nuche Berenguer J , Velazquez Martin M.T , Lopez Gude M.J , Escribano Subias P
Published: November 2020

Introduction

Pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by thrombotic lesions at pulmonary arteries and arteriolar remodeling in distal regions. There is an increase in pulmonary vascular resistance that will lead to heart failure and early death without treatment. Currently, pulmonary endarterectomy (PE) is the potentially curative treatment for this condition. Cardiopulmonary exercise test (CPET) allows to quantify functional improvement after PE. Objective: To analyze changes in CPET and hemodynamic parameters after surgery in a cohort of patients with CTEPH.

Methods

502 patients with CTEPH have been evaluated until December 2018, PE was performed in 255 (51%). In 49 patients, CPET was available before and 6 months after surgery. Residual pulmonary hypertension (RPH) was defined as mean pulmonary arterial pressure ≥30 mmHg evaluated by right cardiac catheterization at 3–6 months after PE.

Results

54% were men, mean age 48±13 years. Two thirds of patients were in functional class II/III at time of diagnosis and with severe hemodynamic and functional profile. Hemodynamics and CPET parameters improved after surgery. However, in patients with RPH they did not improve significantly. Results are shown in table.

Conclusions

PE restores functional capacity in CTEPH, represented by significant improvement in CPET parameters. CPET is emerging as a non-invasive technique suitable of detecting RPH. More studies are needed to confirm this hypothesis.

Funding Acknowledgement

Type of funding source: None
Novel potential diagnostic targets revealed by plasma proteomic analysis in chronic thromboembolic pulmonary hypertension
Authors: Kriechbaum S.D , Wiedenroth C.B , Rudolph F , Peters K , Wolter J.S , Haas M , Rieth A.J , Rolf A , Hamm C.W , Mayer E , Keller T , Liebetrau C
Published: November 2020

Background

Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with poor outcome if untreated, although it is a curable form of pulmonary hypertension (PH). Successful treatment requires an optimized diagnostic work-up.

Purpose

The aim of this study was to identify non-invasive biomarkers that might serve as new diagnostic parameters in the multifaceted pathophysiology of CTEPH.

Methods

The biomarker profile of 64 CTEPH patients who underwent balloon pulmonary angioplasty (BPA) was analyzed prior to and after therapy and compared with that of a healthy control group (CG1, n=25) at baseline. Proteomes were analyzed by semiquantitative screening based on a proximity extension assay of three high-throughput, multiplex immunoassay panels. Serum levels of a subset of biomarkers identified in the screening were additionally measured by immunochemical methods.

Results

Fifty protein biomarkers were found to differ between CTEPH patients and CG1. Eight biomarkers changed significantly after therapy. The overlap of these two groups revealed six targets that were all upregulated in CTEPH at baseline and modifiable by treatment. In this group of biomarkers, the levels of DCN (decorin), HGF (hepatocyte growth factor), BNP (B-type natriuretic peptide), and PAPP-A (papalysin-1) decreased after therapy, whereas SPON-1 (spondin-1) and MEPE (matrix extracellular phosphoglycoprotein) further increased at follow-up. The differences in these biomarkers in CTEPH as well as the dynamics after therapy were confirmed and quantified in enzyme-linked immunosorbent assays.

Conclusions

This study identified 6 biomarkers that might serve as new diagnostic parameters or constitute new therapeutic targets in CTEPH. Further prospective studies will be necessary to determine the specific pathophysiological role of each marker.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): SFB 1213 area CP01
Clinical course of pulmonary embolism patients treated with DOACs: comparing prognosis, recurrent thromboembolism, and major bleeding between patients with and without cancer
Authors: Nakano Y , Imai R , Yoshida M , Shimokata S , Adachi S , Murohara T , Kondo T
Published: November 2020

Background

Venous thromboembolism (VTE) is the third frequent acute cardiovascular syndrome in the Europe and Japan. Since direct oral anticoagulants (DOACs) are widely used now, the morbidity and mortality of pulmonary embolism (PE) patients especially associated with cancer needs to be re-evaluated.

Purpose

We evaluated the clinical course of patients with PE mainly treated with DOACs.

Methods

This retrospective observational study was conducted in a single center. The data were collected from the medical record of consecutive patients who received inpatient treatment of PE. In this study, we have compared PE patients with cancer (cancer PE) to those without cancer (non-cancer PE) and evaluated the mortality, recurrent of VTE and major bleedings.

Results

In total, 140 patients were enrolled: 94 patients were cancer-related, and 46 patients were without cancer (Table). The type of the tumor in cancer PE patients were as follows: gastric 8 (9%), esophageal 5 (5%), pancreatic 12 (13%), lung 14 (15%), lymphoma 2 (2%), gynecologic 17 (18%), renal 2 (2%), bile duct 8 (9%), colon 12 (13%), and others 17 (18%).

Kaplan-Meier curve showed that the cumulative all-cause mortality was significantly higher in the cancer PE group (35/94 (37%) vs. 2/46 (4%), P<0.001 (log rank), HR 10.3 [95% CI:2.5–43.3]). The cumulative incidence of recurrent VTE was significantly higher in the cancer PE group (7/94 (7%) vs. 0/46, P=0.03 (log rank)). There was no significant difference in the cumulative incidence of major bleeding between the cancer PE group and the non-cancer PE group (8/94 (9%) vs. 5/46 (11%)).

Conclusions

The risk of recurrent VTE was still higher in cancer PE patients compared to non-cancer PE patients, although DOACs were used. Meanwhile the incidence of major bleeding was comparable in both groups, the risk of bleeding might be acceptable with using DOACs especially in cancer PE patients.

Figure 1

Funding Acknowledgement

Type of funding source: None
Syk activates the protective mechanism of aorta in the mouse model of aortic dissection
Authors: Hashimoto Y , Aoki H , Majima R , Nakao E , Ito S , Furusho A , Nishida N , Hirakata S , Hayashi M , Fukumoto Y
Published: November 2020

Background

Aortic dissection (AD) is a serious clinical condition that frequently results in fatal outcome. Although recent studies indicate the critical role of inflammation in AD, the molecular pathogenesis of AD is still unclear. Syk is a tyrosine kinase that regulates multiple types of inflammatory cells. Syk is also reported to regulate the function of smooth muscle cells (SMCs), the major component of aortic walls. It is unknown whether and how Syk is involved in AD pathogenesis.

Objective

In the current study, we investigated the role of Syk in AD.

Methods and results

A mouse AD model was created by continuous infusion of beta-aminopropionitrile and angiotensin II (BAPN+AngII) that caused progressive development of AD from day 7, reaching approximately 80% of AD incidence at day 14. Western blot analysis for activated (phosphorylated) Syk (pSyk) revealed Syk activation at day 3 of BAPN+AngII infusion, followed by transient suppression at day 7, and reactivation at day 14. Double immunofluorescence staining for pSyk and smooth muscle alpha actin showed that Syk was active not only in the infiltrating inflammatory cells, but also in SMCs in AD. Treatment of mice with fostamatinib, a specific Syk inhibitor, resulted in more severe AD compared to the vehicle treatment. The AD lesion length was 3.80±0.86 mm in the vehicle group and 8.87±1.69 mm in the fostamatinib group (P<0.05). Fostamatinib worsened the mortality of mice due to the aortic rupture from 0% in the vehicle group and 42% in the fostamatinib group (P<0.05). Transcriptome analysis revealed that fostamatinib suppressed both positive and negative regulators of inflammatory and defense responses. BAPN+AngII infusion caused activation of Stat3, a critical regulator of inflammatory response, which was suppressed by fostamatinib. As we previously reported that Stat3 activation in SMCs is protective against AD, we examined the relationship between Syk and Stat3 in SMCs in culture. BAPN+AngII challenge caused activations of Syk and Stat3, both of which were suppressed by fostamatinib, indicating that Stat3 was under the control of Syk in the AD model and in SMCs.

Conclusions

These findings uncovered the previously unrecognized role of Syk for protecting the aortic tissue in AD pathogenesis, possibly by activating the protective mechanism of aortic walls including Stat3 in SMCs.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant from Japan Society for the Promotion of Science
Endothelial function indicators in patients with critical limb ischemia compared to patients with limb claudication – one-year follow-up period after endovascular revascularisation
Authors: Kaczmarczyk P , Maga P , Januszek R , Frolow M , Belowski A , Nizankowski R , Chlopicki S , Gregorczyk-Maga I
Published: November 2020

Background

Critical limb ischemia (CLI) is the most advanced stage of peripheral arterial disease. Limb revascularization is considered the first line of treatment.

Purpose

The aim of the study was to compare endothelial function and clinical outcomes in CLI and non-CLI patients during a 12-month follow-up period after endovascular treatment (PTA).

Methods

The study was conducted as a prospective, single-centre, follow-up evaluation. The authors recruited 30 CLI and 40 non-CLI patients. The following markers of endothelial dysfunction were evaluated: flow-mediated dilatation (FMD), reactive-hyperaemia index (RHI), arterial pulse-waveform analysis (aPWA) indices and clinical markers such as ankle-brachial index, toe-brachial index and Rutherford scale.

Results

Better clinical improvement may be observed in patients with CLI - the mean Rutherford grade significantly decreased in the CLI group (p<0.001). These patients also have better endothelial response to revascularization – CLI patients continue to have improved RHI up to 6 months after PTA, where in non-CLI patients, improvement was only noted during the first month. The mean FMD value did not change significantly during the follow-up in either of the groups. When comparing selected intervals, the FMD values in the CLI and non-CLI groups improved during the first month of observation and then decreased between the 1st and 6th month of follow-up. Finally, in CLI patients, baseline intima-media thickness predicts the number of reinterventions and major adverse events.

Conclusions

Patients with CLI differ significantly from patients with claudication based on clinical response and endothelial changes after revascularization.

Figure 1. A) Kaplan-Meier survival curves according to CLI and non-CLI status for all study endpoints. B) Kaplan-Meier survival curves according to CLI and non-CLI status for reinterventions.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Collegium Medicum of Jagiellonian University - internal grant
Risk of aortic disease in long-distance cross-country skiers; a study of 209,226 patients
Authors: Larsson J , Sundstrom J , Hallmarker U , James S , Andersen K
Published: November 2020

Background/Introduction

Aneurysmal dilatation and dissection of the aorta are two facets of aortic disease that can lead to major disability and death. Some risk factors for aortic disease are also risk factors for atherosclerotic disease, but the overall causes of aortic disease are diverse and largely unknown. Persons with aortic aneurysms are advised to limit their physical activity, but associations of physical activity with subsequent incidence of aortic disease are little known. Earlier studies have shown strong association of performance in Vasaloppet with incidence of hypertension, a major risk factor for aortic disease.

Aim

To investigate associations of high levels of physical activity with incidence of aortic disease.

Methods

We studied 209,226 participants in a 30–90 km cross-country skiing event (Vasaloppet) and 536,038 persons from the general population, matched to the skiers on age, sex and residence. The number of completed races during the study period and the fastest relative finishing time in a race was recorded. The main outcomes were: 1) aortic disease (defined as thoracic and abdominal aortic aneurysm and/or aortic dissection); and 2) aortic dissection.

Results

During a median time at risk of 8.8 years, 1,442 aortic disease events and 265 aortic dissections occurred. Skiers had lower incidence of aortic disease than non-skiers (Cox proportional hazards ratio [HR] 0.42; 95% confidence interval [CI] 0.36–0.50). An association of better finishing time with aortic disease was observed, with a dose-response gradient from the fastest third (HR 0.25; 95% CI 0.18–0.35), via the slowest third (HR 0.64; 95% CI 0.49–0.82) to the non-skiers (reference group). Among skiers the number of completed races was not associated with incidence of aortic disease. Skiers also had lower incidence of acute aortic dissection (HR 0.61; 95% CI 0.44–0.85) than non-skiers. Low event rate among skiers made conclusions in subgroups unreasonable. All results are adjusted for age, sex, education and income. Results were similar in models accounting for use of antihypertensive and cholesterol-lowering medicines and genetic syndromes associated with aortic disease.

Conclusion

Participation in a long-distance skiing event was associated with lower risk of aortic disease and aortic dissection. Faster completion of the race was strongly associated with lower incidence of aortic disease. If causal, this study suggests that high physical activity and exercise may be protective against aortic disease.

Kaplan-Meier Aorta disease

Funding Acknowledgement

Type of funding source: None
Peripheral artery disease impairs myocardial perfusion through increasing pulse wave reflection: the Northern Shanghai study
Authors: Yu S , Teliewubai J , Fan X , Chi C , Ji H , Blacher J , Zhang Y , Xu Y
Published: November 2020

Background

Peripheral artery disease (PAD) is prevalent and substantially contributes to cardiovascular mortality particularly in the elderly, although the pathophysiological impact of PAD on heart itself still needs further investigation. In theory, PAD can increase pulse wave reflection which is an important determinant of subendocardial viability ratio (SEVR), a valuable estimate of myocardial perfusion as indicated by previous invasive studies. Thus, we hypothesize that PAD impairs myocardial perfusion through increasing pulse wave reflection. In this study, we aim to test this hypothesis in a large cohort from the Northern Shanghai Study.

Methods

A total of 2947 community-dwelling elderly Chinese (43.6% male, mean age: 71.3±5.9 years) were recruited. Ankle-brachial index were measured with the VP1000 device and used to diagnose PAD. Pulse wave reflection was estimated as aortic augmentation pressure (AP). Aortic BP, AP and SEVR were assessed by radial applanation tonometry. Multiple linear regression with SEVR and AP as dependent variable and PAD as independent variable, meanwhile adjusted for other covariates, were performed, respectively.

Results

375 (12.7%) participants presented PAD. Compared to subjects without PAD, those with PAD showed significantly lower SEVR (126 vs. 132, P<0.001) but higher AP (19 vs. 17 mmHg, P<0.001). Multiple regression analysis revealed that both SEVR (regression coefficient [B] = −1.69, P=0.04, R2=0.61) and AP (B=1.19, P=0.04, R2=0.56) significantly associated with PAD, respectively. However, the association between SEVR and PAD was abolished when further adjusted for AP (B=−0.49, P=0.52). Similar results were obtained when inter-leg systolic BP difference was used to diagnose PAD.

Conclusions

PAD significantly and independently associates with myocardial perfusion; moreover, this association is mediated by increased pulse wave reflection. These findings provide a new dimension for understanding the pathophysiological mechanisms of cardiac damage of PAD.

Funding Acknowledgement

Type of funding source: None
Arterial stiffness could reflect increased cardiac load and reduced pulmonary function in the general population
Authors: Murai S , Sugiura T , Dohi Y , Takase H , Mizoguchi T , Yamashita S , Seo Y , Fujii S , Ohte N
Published: November 2020

Background

Pulmonary function is known to decrease with age and reduced pulmonary function has been reported to be associated with all-cause mortality and cardiovascular death. The association between pulmonary impairment and atherosclerosis was reported previously but has not been investigated sufficiently in the general population.

Purpose

We hypothesized that arterial stiffness could reflect increase of cardiac load and reduced pulmonary function. The present study aimed to investigate whether increased cardiac load and reduced pulmonary function could affect arterial stiffness in the general population.

Methods

Subjects undergoing their health check-up were enrolled. Plasma B-type natriuretic peptide (BNP) levels and serum high-sensitivity cardiac troponin I (hs-cTnI) levels were measured to evaluate cardiac load and myocardial damage. Radial augmentation index (rAI) was measured to investigate arterial stiffness using HEM-9000AI device. Subjects with an ST-T segment abnormality on the electrocardiogram, renal insufficiency, cancer, active inflammatory disease, or a history of cardiovascular events and pulmonary disease were excluded. Pulmonary function was assessed using spirometry by calculating forced vital capacity (FVC) as a percentage of predicted value (FVC%-predicted), forced expiratory volume in 1 second (FEV1) as a percentage of predicted value (FEV1%-predicted), and the ratio of FEV1 to FVC (FEV1/FVC).

Results

A total of 1100 subjects aged 57 years were enrolled and their median values of BNP and hs-cTnI were 15.5 and 2.3 pg/ml. The levels of rAI were significantly associated with the levels of BNP after adjustment for possible confounders in multivariate regression analysis, but were not with the levels of hs-TnI. While the parameters of pulmonary function were inversely associated with the levels of rAI and hs-cTnI after adjustment for possible confounders in the multivariate regression analysis, but not with the levels of BNP. The other multivariate regression analyses where BNP, hs-cTnI, parameters of pulmonary function, and the other possible factors were simultaneously included as independent variables revealed that the BNP levels and the FVC%-predicted or FEV1%-predicted, besides age, gender, smoking status, body mass index, blood pressure, heart rate, creatinine, fasting plasma glucose, and triglyceride, were significantly associated with the levels of rAI.

Conclusions

The significant associations of rAI with BNP and pulmonary function were revealed in the general population. These findings support that arterial stiffness could reflect increased cardiac load and reduced pulmonary function, in apparently healthy individuals.

Funding Acknowledgement

Type of funding source: None
Impact of lipoprotein(a) levels on angiographic severity of femoropopliteal lesions
Authors: Yanaka K , Akahori H , Imanaka T , Miki K , Yoshihara N , Kimura T , Tanaka T , Asakura M , Ishihara M
Published: November 2020

Background

High lipoprotein(a) [Lp(a)] levels are a risk factor for peripheral artery disease (PAD). However, the association between Lp(a) levels and angiographic severity of PAD has not been systematically studied.

Purpose

The aim of this study was to assess the impact of Lp(a) levels on angiographic severity of femoropopliteal lesions in patients with PAD.

Methods

We retrospectively analyzed a single-center database including 108 patients (74±8 years, 69% male) who underwent endovascular therapy for de novo femoropopliteal lesions and measured Lp(a) levels before therapy between June 2016 and September 2019. Patients were divided into low Lp(a) [LP(a) <30 mg/dL; 77 patients] and high Lp(a) [LP(a) ≥30 mg/dL; 31 patients] groups. Trans-Atlantic Inter-Society Consensus (TASC) II classification, calcification [referring to peripheral arterial calcium scoring system (PACSS) classification] and lesion length were compared between the groups.

Results

Median Lp(a) was 16 (7–31) mg/dL.The prevalence of TASC II class D (13% vs 38%, P<0.01) and severe calcification (PACSS 4) (6% vs 23%, P=0.02) was significantly higher and lesion length was longer (123±88 mm vs 175±102 mm, P<0.01) in the high Lp(a) group than in the low Lp(a) group.(Table and Figure) In multivariate analysis, Lp(a)≥30 was an independent predictor for TASC II class D (HR=3.67, P=0.02) and PACSS 4 (HR=4.97, P=0.02) prevalence.

Conclusion

Lp(a) was associated with angiographic severity of femoropopliteal lesions in patients with PAD.

Comparison of angiographic severity

Funding Acknowledgement

Type of funding source: None
Serum Lipoprotein(a) levels on clinical outcomes after endovascular therapy
Authors: Tomoi Y , Soga Y , Hiramori S , Ando K
Published: November 2020

Background

While lipoprotein (a) (Lp(a)) is an independent predictor of atherosclerotic diseases involving the coronary and cerebrovascular arteries, its prognostic value in patients with peripheral artery disease (PAD) remains still unclear.

Objective

The aim of study is to determine the role of Lp(a) levels after endovascular therapy (EVT).

Methods

This study was prospective observational study. From September 2016 to April 2019, 676 the patients (873 limbs) who underwent EVT for de-novo PAD were enrolled. We divided into Lp(a) levels ≥40 mg/dl (high Lp(a) group; n=129) and <40 mg/dl (low Lp(a) group; n=547). Outcome measures were major adverse cardiovascular events (MACE; all-cause death, myocardial infarction and stroke), and major adverse limb events (MALE; repeat revascularization for limb and major amputation) at 1 year. Major amputation defined as above forefoot amputation due to vascular cause.

Results

The mean follow-up period was 14.3±8.9 months. Serum Lp(a) levels before EVT were 27.2 (10.0–36.0 mg/dl). High Lp (a) group was significantly older, higher prevalence of history of stroke, chronic kidney disease, and multi-vessel lesions. Cumulative incidence of MACE at 1 year was not significantly between two groups (p=0.53, log-rank test), whereas cumulative incidence of MALE at 1 year was significantly higher in high Lp (a) group (p=0.04, log-rank test). However, after adjusting for prespecified risk factors, high Lp (a) group was not independent predictor in MALE at 1 year.

Conclusion

High Lp (a) might not be associated with cardiovascular events and limb prognosis after EVT for PAD in early phase.

Funding Acknowledgement

Type of funding source: None
Use of dual layered stents in endovascular treatment of extracranial stenosis of the internal carotid artery: one year results of a patient-based meta-analysis of 4 clinical studies
Authors: Stabile E , De Donato G , Musialek P , Deloose K , Nerla R , Sirignano P , Mazurek A , Mansour W , Fioretti V , Esposito F , Chianese S , Bosiers M , Speziale F , Micari A , Esposito G
Published: November 2020

Background

Small sized clinical studies evaluating one year outcomes of CAS performed with two available DLS, Roadsaver® (RS) and CGuard® (CG), have been published.

Purpose

To evaluate one year safety and efficacy of dual layered mesh covered carotid stent systems (DLS) for carotid artery stenting (CAS).

Methods

We performed an individual patient-level meta-analysis including studies enrolling more than 100 CAS with DLS. Primary endpoint was the death and stroke rate; secondary endpoints were restenosis and in-stent thrombosis rates at one year.

Results

Patients were divided in two groups according to DLS (RS N=250; CG N=306). At one year, 11 patients died (1.97%), 7 patients in the group RS (2.8%) and 4 patients in the CG one (1.31%), 10 strokes occurred, 4 in the group RS (1.6%) and 6 in the CG one (1.96%). Overall death and stroke rate was 3.77% (N=21), 11 events in the group RS (4.4%) and 10 in the CG group (3.27%). Symptomatic status was the only predictor of death and or stroke.

At one year restenosis occurred in 12 patients (2.1%), 10 in the group RS (4%) and 2 in the CG one (0.65%) (p=0.007). In stent thrombosis occurred in 1 patient (0.18%) of the group CG (0.32%). RS use was the only independent restenosis predictor.

Conclusions

This study suggests that DLS use for CAS is associated to a low one year death and stroke rate and specific DLS stent use could affect restenosis rate.

Funding Acknowledgement

Type of funding source: None
Height and risk of ischaemic stroke subtypes: a Mendelian randomisation study
Authors: Linden A , Clarke R , Hopewell J.C , Whiteley W.N , Walters R.G , Li L , Chen Z , Parish S
Published: November 2020

Background

Taller adult height is associated with lower risks of ischaemic heart disease in both conventional and Mendelian randomisation studies, providing support for a causal association, but the associations of height with ischaemic stroke and ischaemic stroke subtypes are uncertain.

Purpose

To examine the causal relevance of height for ischaemic stroke and ischaemic stroke subtypes.

Methods

Two-sample Mendelian randomisation analyses were used to examine the associations of height with: (i) ischaemic stroke and ischaemic stroke subtypes in MEGASTROKE (using summary data from 34 217 ischaemic stroke cases), and with (ii) established cardiovascular and other risk factors using individual data from 336 433 participants in UK Biobank and 57 785 in the China Kadoorie Biobank. Instruments for Mendelian randomisation were constructed from up to 3280 height-associated genetic variants, previously identified as having genome-wide significant effects on height.

Results

Genetically-determined taller height was inversely associated with ischaemic stroke (3% [95% CI: 1–6] lower risk per 1 standard deviation taller height) in MEGASTROKE but this masked much stronger opposing associations on risks of different ischaemic stroke subtypes: 15% (95% CI: 9–21) higher risk of cardioembolic stroke, 10% (4–15) lower risk of large-artery atherosclerotic stroke, and 15% (10–20) lower risk of small-vessel stroke (Figure). Genetically-determined taller height was strongly associated with atrial fibrillation and higher lean body mass and lung function but more weakly associated with lower levels of LDL cholesterol and blood pressure.

Conclusions

The findings support a causal association between taller adult height and risk of atrial fibrillation and cardioembolic stroke. The opposing associations of height with other ischaemic stroke subtypes provide further support for considering ischaemic stroke subtypes as distinct diseases in both research and clinical practice.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Medical Research Council, British Heart Foundation
Simultaneous cardio-cerebral embolization. A prospective study
Authors: Mione V , Leclercq T , Bejot Y , Lenfant M , Maza M , Zeller M , Cochet A , Cottin Y
Published: November 2020

Background

Atrial Fibrillation (AF) is a common cause of ischemic stroke but also the most common cause of Coronary Artery Embolism (CE). Many previous case of coexistence of coronary and cerebral embolism have been reported in the literature but in specific situations were clinical signs of stroke but also indisputable clinical and/or electrocardiographic (ECG) signs leaded to the realization of coronarography in emergency.

Objectives

The aim of the study was to determine the existence of simultaneous cardio-cerebral embolization associated in patients with ischemic embolic stroke on de novo AF, in the absence of clinical and/or ECG signs evocative of myocardial infarction (MI).

Methods

We prospectively included patients hospitalized in our institution for ischemic embolic stroke on de novo AF. Patients with history of ischemic disease were excluded. All patients had: 1/ troponin assay; 2/ Cardiac Magnetic Resonance (CMR) imaging with Late-Gadolinium Enhancement (LGE) in order to detect myocardial infarction; 3/ coronary exploration by cardiac CT scan or coronarography to exclude patients with significant coronary lesion.

Results

Between January and December 2019, 32 patients were included. Of them, 15 had subendocardial or transmural LGE on CMR, evocative of MI. Among these 15 MIs we classified acute MIs according to the level of troponin at the admission in stroke unit, the coronarography and T2 hypersignal on cardiac MRI. Median delay of cardiac MRI was 6 days for acute MIs.

CE was clearly identified by coronarography for 4 patients with acute simultaneous cardio-cerebral infarction (56%). The MRI abnormalities showed that lesions of all MIs were transmural, relatively small (average 1.3±0.44 segments) and in most cases in the inferior cardiac wall (47%) and these abnormalities were comparable in sequelae and acute MI. Moreover, the left appendage morphology was a “cactus” in 62.7% of simultaneous acute cardio-cerebral infarction and only 33% in patients without MI or sequelae MI. Strokes were mainly localized in the superficial territory of the middle cerebral artery, and were similar in patients with or without MI. In addition, the rate of sequelae strokes was higher in isolated stroke group than “cardiocerebral infarction” (29.5% versus 13.3%).

Conclusion

Simultaneous acute cardio-cerebral infarction is not uncommon, diagnosed in 22% of our prospective cohort of embolic stroke. Cardiac MRI may help us to diagnose a concomitant cardiac embolization and evaluate the prognosis. Unfortunately optimal therapeutic strategy of these patients is still unknown.

Flow Chart

Funding Acknowledgement

Type of funding source: None
Left-sided valvular heart disease associated with poor functional outcomes in patients with acute ischaemic stroke undergoing endovascular thrombectomy
Authors: Ngiam N , Tan B.Y.Q , Sia C.H , Chan B.P.L , Anil G , Yang C.L , Poh K.K , Yeo L.L.L , Sharma V.K
Published: November 2020

Background

Valvular heart disease (VHD) may be an important comorbidity acute ischemic stroke (AIS), adversely affecting cerebral haemodynamics and consequently limiting functional recovery after endovascular thrombectomy (EVT). We examined the clinical profile and outcomes in patients with or without VHD who underwent EVT for AIS.

Methods

Consecutive patients (n=224) who underwent EVT for AIS were examined. All patients underwent transthoracic echocardiography within 6 months of AIS. The patients were divided into those with left-sided VHD (at least moderate severity of aortic valve or mitral valve stenosis or regurgitation) and those without. Univariate and multivariate analyses were employed to compare clinical profile and outcomes.

Results

There were 47 (20.9%) patients with VHD. Of these, 31 (66.0%) had mitral regurgitation, 15 (31.9%) had aortic stenosis, 8 (17.0%) had aortic regurgitation and 6 (12.8%) had mitral stenosis. VHD patients had a higher prevalence of atrial fibrillation (68.1% vs 43.5%, p=0.003) compared to those without, but stroke severity was similar. They had higher prevalence of pathological left ventricular (LV) remodelling, with larger end-diastolic volume index (77.9±34.5 vs 61.1±19.9ml/m2, p<0.001) and LV mass index (116.4±32.7 vs 99.8±32.2g/m2, p=0.002). Despite similar rates of recanalisation, VHD patients had poorer functional outcomes (mRS>2) at 3 months (68.1% vs 50.3%, p=0.029). On multivariable analyses, VHD remained independently associated with poor functional outcomes (adjusted OR 2.42, 95% CI 1.08–5.43), after adjusting for age, stroke severity and recanalisation rates.

Conclusion

VHD may be associated with poorer functional outcomes in patients with AIS undergoing EVT, despite similar rates of successful recanalisation.

Ordinal shift analyses

Funding Acknowledgement

Type of funding source: None
Utility of transcranial color flow imaging for detecting high risk morphology of patent foramen ovale in patients with cerebral infarction
Authors: Chino S , Mochizuki Y , Toyosaki E , Ota M , Mizuma K , Nohara T , Sawai A , Shinke T
Published: November 2020

Background

Micro-bubble test by using transcranial color flow imaging (TCCFI) is important as a screening evaluation for diagnosis of paradoxical cerebral embolism which requires the proof of right to left shunt at atrial septum. In addition, high risk features of patent foramen ovale (PFO) that may allow thrombus to easily pass through the PFO itself were previously reported. However, little is known about the association between the degrees on micro-bubble test by TCCFI and the features of high risk PFO.

Purpose

Our aim is to clarify the relationship between the degree of micro-bubble test in TCCFI and the morphology of PFO from transesophageal echocardiography (TEE).

Methods

Seventy-seven patients in whom cardiogenic embolism was strongly suspected by neurologists in Showa University from April to December in 2019 were retrospectively studied. 55 patients underwent both TCCFI and TEE with sufficient Valsalva stress. TCCFI grade of micro-bubble test was classified into 3 groups (A: none, B: small, and C: massive), in which signified “none” is no sign of micro-embolic signals (MES) within 30 seconds, “small” is 1 or more MES, and “massive” is so much MES look like a curtain (Figure). Evaluated high risk characteristics of PFO for cerebral embolism as previously reported were as follows; (1) tunnel height, (2) tunnel length, (3) total excursion distance into right and left atrium, (4) existence of Eustachian valve or Chiari network, (6) angle of PFO from inferior vena cava (7) large shunt (20 or more micro-bubbles).

Results

Of all TCCFI-positive patients (n=32; Group B=19, Group C=13) with cerebral embolism, PFOs were detected in 23 patients in TEE. Therefore, the sensitivity and specificity of TCCFI to PFO were 87% and 63% (AUC=0.75, p<0.001, respectively). Interestingly, all 13 patients (Group C) had manifest PFOs. Moreover, group C include 2 patients with platypnea orthodeoxia syndrome in which hypoxia in the sitting position becomes apparent. Among PFO-positive patients, tunnel height, length, total excursion distance into right and left atrium, and large shunt in TEE were significantly larger in Group C than Group B (p<0.05).

Conclusions

Micro-bubble test by using TCCFI may have screening advantages in predicting paradoxical cerebral embolism, high-risk morphology of PFO, and platypnea orthodeoxia syndrome.

Figure 1

Funding Acknowledgement

Type of funding source: None
Practice patterns, feasibility and efficacy of coronary artery angiography using distal radial approach
Authors: Kajiya T , Takaoka J , Mukai R , Inoue T , Ninomiya T , Kitazono K , Miyamura A , Atsuchi Y , Atsuchi N , Ohishi M
Published: November 2020

Background

Most patients undergo coronary angiography by transradial approach. However, recently distal radial approach has been introduced as a novel approach for coronary angiography and intervention. There is uncertainty on the feasibility and safety of distal radial approach for coronary angiography.

Methods

All consecutive 1450 coronary angiography cases (distal radial approach 237 cases, conventional transradial approach 1213 cases) between October 2018 and December 2019 were included in this study. Emergency coronary angiography cases and ad hoc coronary intervention cases were excluded. Patients were stratified into distal radial approach and conventional radial approach subgroups. Baseline characteristics, contrast amount, procedure time, radiation amount, fluoroscopy time, and complications in catheterization laboratory were statistically analyzed.

Results

There were no significant differences in age and gender between distal radial vs transradial groups: mean age, 70.8±10.5 vs 70.8±11.0 years; % of males, 77.2% vs 66.9%. Procedure time was significantly shorter in distal radial approach group (28.7±13.3 min vs 32.3±14.2 min, p<0.05) and total radiation amount during procedure was significantly less in distal radial approach group (366.4±189.5 ml vs 412.9±220.3 mGy, p<0.05).

Conclusions

Coronary angiography with distal radial approach decreases the procedure time and total radiation amount. It is feasible and safe in most stable patients.

Funding Acknowledgement

Type of funding source: None
The comparison of the chronic-phase vascular healing between bioabsorbable and durable polymer drug eluting stent by using optical coherence tomography
Authors: Yamakami Y , Kimura S , Hara K , Ohmori M , Tateishi R , Kaneda T , Shimada H , Manno T , Isshiki A , Shimizu M , Fujii H , Suzuki M , Sasano T
Published: November 2020

Background

Bioabsorbable polymer drug eluting stents (BP-DESs) were designed to reduce a vascular inflammatory reaction compared to durable polymer drug eluting stents (DP-DESs). However, few studies have compared vascular responses to BP-DESs and DP-DESs.

Methods

We enrolled 88 consecutive patients with single culprit coronary artery lesions (31 lesions with acute coronary syndrome) undergoing a single stent-implantation. BP-DESs and DP-DESs were implanted in 50 (57%) and 38 patients (43%), respectively. All lesions underwent optical coherence tomography examination at chronic phase and intrastent OCT findings at the follow-up were evaluated in every 1-mm cross-sections (CSs).

Results

A total of 1887 CSs (BP-DES: 1096, DP-DES: 791) were analyzed. The median period of follow-up OCT was 293 (250–374) days. There were no differences in the patient, lesion, and initial clinical presentation of acute coronary syndrome (ACS). BP-DESs had significantly higher percent neointimal hyperplasia area, defined as neointimal hyperplasia area divided by stent area x 100 (18.4±9.0% vs. 16.1±9.9%, p<0.001), fewer malapposed struts (1.7% vs. 3.9%, p=0.005), fewer uncovered struts (3.6% vs. 5.8%, p=0.02) but higher frequency of superficial low intensity neointima (LIN) (7.7% vs. 3.4%, p<0.001). Multivariate logistic analysis showed that BP-DES (OR: 2.5, 95% CI: 1.49–4.08, p<0.001) and the initial clinical presentation of ACS (OR: 2.31, 95% CI: 1.47–3.62, p<0.001) are independent predictive factors for LIN.

Conclusion

BP-DESs showed homogenous neointimal growth and complete stent coverage quantitatively. Meanwhile, the significant relationships of BP-DES with LIN may suggest that the neointimal quality remains immature in BP-DESs in this period.

Funding Acknowledgement

Type of funding source: None
Intravascular imaging to guide lithotripsy in concentric and eccentric calcific coronary lesions
Authors: Nardi G , Mattesini A , Martellini A , Sorini Dini C , Meucci F , Stolcova M , Hamiti B , Di Mario C
Published: November 2020

Background

Calcified coronary lesions still represent a challenge for coronary angioplasty, with sub-optimal acute PCI results causing more frequent late stent failure.

Purpose

The study aimed at the evaluation of the immediate procedural outcome of a novel treatment algorithm based on IVUS and/or OCT and including lithotripsy into a real-world consecutive based on intravascular imaging assessment by IVUS or OCT.

Methods and results

Thirty-one calcified stenoses (28 patients) out of a total of 455 lesions in 370 patients treated between November 2018 and May 2019 met the clinical and angiographic criteria for treatment with IVL under intravascular imaging guidance. Patients were divided into two subgroups depending on the calcium arc measured with intravascular imaging. Twenty lesions showed a calcium arc greater than 180 degrees (289±53 degrees) and 11 lesions smaller than 180 (140±24 degrees). The following parameters were assessed with OCT and/or IVUS: post stent minimal lumen area (MLA) and area stenosis (AS), incomplete strut apposition (ISA), eccentricity index, strut fracture, and edge dissection. After optimization a satisfactory lumen enlargement (acute gain 1.28±0.46 mm; minimal stent area 7.09±2.77 mm2) was observed with good stent expansion (residual area stenosis <20% in 29 lesions, 93.5%) and OCT calcium fractures in 71% of cases. Peri-procedural complications were limited to one dissection at the distal edge requiring an additional stent and 3 peri-procedural myocardial infarctions. There were no in-hospital coronary perforations, no pericardial effusions, no stent failure or thrombosis, no deaths.

Conclusions

A standardized algorithm applying multimodality imaging to guide selection and application of IVL facilitated second generation DES implantation with final post-dilatation delivers excellent immediate procedural results and patient outcome, both in concentric or eccentric calcifications.

Funding Acknowledgement

Type of funding source: None
Impact of SYNTAX score 2 on 7-year clinical outcomes in patients treated with cobalt-chromium everolimus-eluting stent
Authors: Hiromasa T , Kuramitsu S , Yamaji K , Domei T , Hyodo M , Soga Y , Shirai S , Ando K
Published: November 2020

Background

Impact of SYNTAX score II (SSII) on long-term clinical outcomes after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation remains unclear.

Methods

Between February 2010 and May 2011, 1064 consecutive patients with 1440 lesions were treated only with CoCr-EES implantation. Of these, the SSII was calculated in 1013 patients with 1345 lesions. Patients were divided into the tertile group: Tertiles for SSII (low SSII [12–28.9], n=334; intermediate SSII [29–39.1], n=339; and high SSII [39.2–80.8], n=340). We assessed the cumulative 7-year incidences of major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, definite stent thrombosis, and clinically driven target lesion revascularization (CDTLR) based on SSII groupings.

Results

Cumulative 7-year incidence of MACE was significantly higher in the high SSII group than in the other groups (34.1% vs. 18.6% vs. 17.2%, p<0.001). The cumulative incidence of cardiac death, myocardial infarction and stent thrombosis were significantly higher in the high SSII group than in the other groups (22.1% vs. 2.0% vs. 5.3%, p<0.001; 6.6% vs. 4.9% vs. 1.7%, p=0.01; 2.9% vs. 1.7% vs. 0.3%, p=0.03, respectively). The cumulative incidence of CDTLR was similar between the groups (15.2% vs. 12.8% vs. 15.7%, p=0.57). High SSII group (hazard ratio [HR] 2.18 [vs. low SS], 95% confidence intervals [CI]: 1.56–3.06, p<0.001) and diabetes mellitus (HR 1.37, 95% CI: 1.04–1.81, p=0.03) were predictors of 7-year MACE.

Conclusions

SSII has significantly impact on 7 years clinical outcomes after CoCr-EES implantation.

Cumulative incidence of MACE

Funding Acknowledgement

Type of funding source: None