bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of arterial damage in vascular Ehlers-Danlos syndrome: a retrospective multicentric cohort
Authors: Adham S , Legrand A , Bruno R M , Billon C , Dalens V , Boutouyrie P , Mazzella J M , Gueguen S , Frank M , Mirault T , Jeunemaitre X
Published: October 2022

Background

Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder due to pathogenic variants in the COL3A1 gene, leading to medium-size artery (MSA) dissection, aneurysm, and rupture with a poor prognosis. Conversely, aortic lesions are rarer and less investigated.

Purpose

To describe the association between the distribution of MSA and aortic lesions and the type of COL3A1 variants in a multicentric cohort of vEDS patients.

Methods

Analysis of the 330 vEDS adult patients from the French RaDiCO SEDVASC registry. At the time of the study, 87% were alive, 60.3% were index cases and 60.0% females. Median age at molecular diagnosis was 36 years (IQR 24.3–46.8). COL3A1 variants were identified using NGS and/or Sanger sequencing and classified according to their functional consequences: 80.6% dominant-negative (DN) and 19.4% leading to haplo-insufficiency (HI). Computed tomography angiography (CTA) was systematically performed during the initial work-up of patients. Carotid mechanics was also assessed by echotracking in a subgroup of 133 patients.

Results

Arterial lesion history was reported in 82.4% of the patients (N=272), with 227/272 patients (83.5%) having MSA lesions alone, 9 (3.3%) aortic lesions alone and 36 (13.2%) both. DN variant was associated with higher prevalence of arterial lesions than HI variant (P 0.044), especially on supra-aortic trunks and renal arteries (P 0.018 and P 0.0003 respectively). Importantly, the higher prevalence of aortic lesions observed in HI patients with arterial lesions versus DN patients (P 0.027) was not significantly different when adjusted for age (P 0.559). Carotid Young's modulus was lower in DN than HI patients (P 0.014), in association with the higher incidence of MSA lesions in this genotype group.

Conclusion

The prevalence of aortic lesions is not influenced by the COL3A1 genotype when adjusted for age. vEDS patients with DN variants have a higher frequency of MSA lesions especially in supra-aortic trunks which is associated with a lower carotid stiffness, suggesting a need for an optimal care for this subgroup of patients.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): French National Research Agency under the specific programme “Investments for the Future”, cohort grant-agreement ANR-l0-COHO-03-01
In hospital outcomes among diabetics undergoing transcarotid artery revascularisation vs transfemoral carotid artery stenting & carotid endarterectomy
Authors: Hasnie A , Hasnie A , Adefisoye J , Magee K , Allaqaband S , Jan M F , Bajwa T K , Haddadian B
Published: October 2022

Background

Transcarotid artery revascularisation (TCAR) is a novel procedure to intervene on carotid artery stenosis. It has previously shown to have lower rates of periprocedural adverse events compared to transfemoral carotid artery stenting (TFCAS) and carotid endartectomy (CEA). To date, no study has examined outcomes among diabetics undergoing TCAR compared to TFCAS and CEA.

Purpose

We sought to determine the rates of adverse periprocedural outcomes related to TCAR, TFCAS and CEA in diabetics.

Methods

The Vascular Quality Initiative Database was queried for all patients from March 2009 to April 2021 for diabetic patients undergoing carotid artery revascularisation via TCAR, TFCAS or CEA. Baseline demographic information as well as periprocedural outcomes were obtained.

Results

A total of 57,716 diabetic patients underwent carotid artery revascularisation. Of these 11.3% underwent TCAR (n=6569), 8.1% (n=4703) underwent TFCAS, and 80.4% (n=46,444) underwent CEA. 39% (n=22,528) were female and 87.3% (n=50,377) were white. Compared to TFCAS, TCAR demonstrated lower rates of stroke (1.6% vs 2.2%, p=0.026), stroke/transient ischemic attack (2.2% vs 3.0%, p<0.001), and death (0.4% vs 1.3%, p<0.001) but remained higher than CEA for both stroke (1.6% vs 1.3%), stroke/TIA (2.2% vs 1.9%) and death (0.4% vs 0.3%).

Conclusions

TCAR appears to be a safe revascularisation procedure for carotid artery stenosis with lower rates of stroke, stroke/TIA, and death in diabetics compared to TFCAS. However, rates remain higher than CEA. TCAR may thus be a viable alternative in diabetics who otherwise would be poor candidates for revascularisation via CEA.

Funding Acknowledgement

Type of funding sources: None.
Neuroimaging evaluation of unilateral asymptomatic carotid plaque ulceration: preliminary results of the Carotid Artery Multimodality imaging Prognostic study
Authors: Masini G , Gargani L , Napoli V , Cosottini M , Chiappino D , Orlandi G , D'Amelio C , Todaro P , Galeotti G , Bort I R , Baldini M , Aghakhanyan G , Erba P , Palombo C , De Caterina R
Published: October 2022

Background

Carotid plaque ulceration has been associated with imaging characteristics of high risk of future events (plaque vulnerability) in patients with a significant degree of stenosis, while little is known about its role in patients with a lesser degree of stenosis and its association with markers of vascular inflammation.

Purpose

We evaluated the association between imaging characteristics of plaque vulnerability and vascular inflammation detected by different imaging tests.

Methods

One hundred and seven patients with unilateral asymptomatic carotid artery stenosis (40–60% detected by Doppler ultrasound (DUS)), enrolled in the ongoing Carotid Artery Multimodality Prognostic (CAMP) study were prospectively evaluated with computed tomography angiography (CTA), contrast-enhanced magnetic resonance imaging (CEMRA) and, in a subgroup of patients, with 18-F-fluorodeoxyglucose positron emission tomography (PET). Plaque ulceration was detected by CTA. Variables are expressed as median (1st–3rd quartiles) and number (percentages).The Student's t-test or Mann-Whitney and Chi square or Fisher's exact test were used to study associations among variables.

Results

An ulcerated plaque was present in 35% patients (n=33) of those undergoing CTA (n=94), while intraplaque hemorrhage and lipid-rich necrotic core were present in 9% and 15% of those undergoing CEMRA. Compared with patients with non-ulcerated plaques, those with an ulcerated plaque had a significant higher degree of stenosis at DUS, a higher target to background ratio (TBR) at 18F-FDG-PET and a higher high-sensitivity cardiac troponin (cTn) T.

Conclusions

Plaque ulceration is common and associated with higher degree of stenosis, higher indices of wall inflammation and higher serum markers of myocardial injury.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Regione Toscana
Causes of death in an unselected population with first time venous thromboembolism
Authors: Lonnberg F , Farm M , Andre H , Okas M , Roos A , Siddiqui A J
Published: October 2022

Background and aim

Causes of death in an unselected population with first-time community acquired venous thromboembolism (VTE) is largely unknown in the contemporary era of direct oral anticoagulation (DOAC).

Material and methods

All patients >18 years of age who had a visit for any medical reason to any of 5 different emergency departments (EDs) in our city from 1st January 2016 to 31st December 2017 were included. We identified all patients with any incident VTE (deep vein thrombosis (DVT) and/or pulmonary embolism (PE)) at the time of the ED visit. Cox regression models were used to estimate hazards ratios (HR) with 95% confidence intervals (CIs) for all-cause mortality and cause-specific death in patients with any VTE, using all other ED patients as the reference group.

Results

In total, 409,971 patients had an ED visit during the study period, of whom 2% were diagnosed with VTE (DVT= 4,817, PE= 3,147). During a median follow up of 2.6 years, 1265 (16%) and 25,191 (6.3%) patients died within the VTE and reference group respectively. The adjusted risk of cancer related death was nearly 3-fold in patient with DVT (HR 2.7; 95% CI, 2.4–3.1), and 5-fold in PE patients (HR 4.6; 95% CI, 4.1–5.1 respectively), compared to the referent. A diagnosis of PE at the ED visit was associated with a 50% increased risk of cardiovascular death (HR 1.5; 95% CI, 1.2–1.9).

Conclusion

Patients with VTE have a high risk of all-cause mortality, including non-cancer related death and cardiovascular death despite improvements of diagnosis and treatment with DOAC. The study findings indicate that further improvement is needed in VTE management.

Funding Acknowledgement

Type of funding sources: None.
Polygenic risk scores for mood disorders predict future strokes in women: a Mendelian randomization study
Authors: Goncalves I , Borne Y , Edsfeldt A , Wang Y , Pan M , Regeneron Genetics Center  , Mellander O , Engstrom G , Sun J
Published: October 2022

Objectives

Mood disorders and strokes are often comorbid, and their health toll worldwide is huge. This study characterizes prognostic and etiological roles of mood disorders in stroke.

Methods

We tested if genetic susceptibilities for mood disorders could predict future strokes using the Malmö Diet and Cancer cohort (24 631 individuals). Additionally, Mendelian randomization was employed to further examine the causality using summary statistics from large genome wide association studies (mood disorders: up to 287,932 individuals; strokes: up to 446,696 individuals).

Results

Among 24,366 stroke-free participants at baseline, 2,632 individuals developed strokes, 2,172 of them ischemic, during a follow-up of up to 25 years. After all adjustments, participants in the highest quintile (5th quintile) of polygenic risk scores (PRS) for mood disorders had 1.46x (95% confidence interval (CI): 1.22–1.74) higher risk of strokes and 1.45x (95% CI: 1.19–1.77) higher risk of ischemic strokes compared to the lowest quintile (1st quintile) of PRS in women. Univariable and multivariable Mendelian randomization analyses showed that mood disorders had causal effect on smoking (odds ratio (OR) = 1.19, 95% CI: 1.07–1.31), type 2 diabetes mellitus (T2D, OR=1.22, 95% CI: 1.04–1.43) and women's body mass index (BMI, coefficient = 0.11, 95% CI: 0.01–0.21), whereas causal effects for smoking, T2D and BMI on stroke/ischemic stroke were consistently observed.

Conclusion

Our results suggest that mood disorders can cause stroke through smoking, T2D and BMI. Using PRS, women, who benefit from prevention and treatment of smoking, T2D and BMI, could possibly be early identified to prevent mood disorders and strokes.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Swedish Research Council, Swedish Heart and Lung Foundation, Skåne University Hospital Foundations, Lund University Diabetes Center - Industrial Research Center from the Swedish Foundation of Strategic Research, Region Skåne Grants, Swedish Stroke Foundation, Swedish society of medicine, Söderström König Foundation, Emil and Wera Cornell Foundation, Hjelt Foundation, and Diabetes Research and Wellness Foundation Sweden.
Effect of mitral regurgitation in stroke risk in patients with nonrheumatic atrial fibrillation
Authors: Dominguez Erquicia P , Raposeiras-Roubin S , Abu-Assi E , Ledo-Pineiro A , Gonzalez-Garcia A , Iglesias-Otero C , Garcia-Campo E , Iniguez Romo A
Published: October 2022

Background

Atrial fibrillation (AF) carries a thrombotic risk related to blood stasis produced in left atrium. In patients with rheumatic valve disease and AF, the presence of severe mitral regurgitation (MR) has been shown to reduce the risk of atrial thrombosis and stroke. In patients without rheumatic disease, the results are controversial.

Purpose

Our objective is to analyze the association between mitral regurgitation and the incidence of stroke.

Methods

We analyzed data from the retrospective registry CardioCHUVI-AF, which includes 15,720 patients with AF (excluding mechanical prostheses or rheumatic valvular disease) in the Vigo area, from 2014 to 2018. We grouped the patients according to the MR grades: grade 0–2 (15,194 patients) and grades 3–4 (526 patients). We performed propensity score matching analysis obtaining 2 groups of 511 patients. We analyzed the association between MR and stroke with a competitive risk model, being death the competitive event.

Results

During a median follow-up of 4.90 years (IQR 2.85–4.93), 859 (5.5%) patients suffered a stroke. The stroke incidence rate was 1.30 per 100 person-years (95% CI: 1.21–1.39), with no differences between the MR groups. In the univariate analysis, no relationship was observed between the MR grades and stroke (sHR 1.12, 95% CI: 0.79–1.60, P=0.530). After the propensity score matching analysis no significant association was observed between the MR grades and stroke (sHR 0.93, 95% CI: 0.57–1.53, P=0.775) (Figure 1 and 2). This same relationship was evaluated by subgroups of interest: oral anticoagulation, prior heart failure, left ventricular ejection fraction <40%, aortic valve disease, and left atrial dilatation, with results consistent with the overall sample (Figure 2).

Conclusions

In our large registry of patients with AF, we did not find a protective effect of significant mitral regurgitation (grades 3–4) on the risk of stroke.

Funding Acknowledgement

Type of funding sources: None.
FFRCT and recurrent symptoms in patients with stable chest pain
Authors: Madsen K T , Noergaard B L , Oevrehus K A , Parner E , Jensen J M , Grove E L , Fairbairn T A , Nieman K , Patel M , Rogers C , Mickley H , Thomsen K K , Boetker H E , Leipsic J , Sand N P R
Published: October 2022

Introduction

The major benefit of coronary revascularization when compared with optimal medical treatment (OMT) in patients with stable chest pain (CP) relates to improvement of symptoms and reduction of reinterventions. Non-invasive methods are warranted to discriminate between patients at low and high risk of recurrent CP for subsequent guidance of antianginal treatment (invasive or OMT).

Purpose

To evaluate the association between coronary CT angiography (CTA) derived fractional flow reserve (FFRCT), recurrent CP and quality of life (QOL) in patients with new onset stable CP and stenosis by CTA.

Methods

Multicenter cohort 3-year follow-up sub-study of 769 patients from the Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care (ADVANCE) registry at three Danish sites, the “ADVANCE-DK Registry”. All patients had at least one ≥30% coronary stenosis by CTA and underwent subsequent core laboratory FFRCT analysis by HeartFlow. An abnormal FFRCT was defined as the lowest in vessel FFRCT value ≤0.80. Patients were classified according to completeness of revascularization by FFRCT: 1) completely revascularized (CR-FFRCT), all coronary arteries with an abnormal FFRCT test result revascularized; 2) incompletely revascularized (IR-FFRCT), ≥1 coronary artery with an abnormal FFRCT test result not revascularized. All patients completed the Seattle Angina Questionnaire (SAQ-7), the EuroQol questionnaire (EQ-5D-5L) and graded (0–100) overall health using the EQ VAS scale at 3-year follow-up. Recurrent CP was defined as CP within the last 4 weeks prior to this follow-up.

Results

Patient characteristics are given in Table 1. At follow-up 23% patients reported recurrent CP. An abnormal vs a normal FFRCT increased the risk of recurrent CP, 27% vs 15%, RR: 1.82; 95% CI: 1.31–2.52, p<0.001. Amongst patients with abnormal FFRCT, revascularization (+/−) was associated to a numerical, but not statistical significantly, reduced risk of recurrent CP, 23% vs 30%, RR: 0.76; 95% CI: 0.56–1.03, p=0.07. IR-FFRCT vs CR-FFRCT had a higher risk for recurrent CP, 31% vs 13%, RR: 2.34; 95% CI: 1.48–3.68, p<0.001, whilst no difference was observed for CR-FFRCT vs normal FFRCT, 13% vs 15%, RR: 0.92; 95% CI: 0.54–1.54, p=0.74. IR-FFRCT vs CR-FFRCT or normal FFRCT, had lower SAQ-7, EQ-5D-5L and EQ-VAS scores, Table 1, all p<0.005. Scores for three selected SAQ-7 domains are shown in Figure 1. Use of antianginal medicine was higher in IR-FFRCT compared to CR-FFRCT and normal FFRCT, mean ± SD: 1.2±0.05 vs 1.0±0.04, p=0.02.

Conclusion

An abnormal FFRCT identifies patients with an increased risk of recurrent CP up to 3 years after index testing. Completeness of revascularization by FFRCT reclassifies patients with abnormal FFRCT into groups with low and high risk for recurrent CP and impaired QOL.

Funding Acknowledgement

Type of funding sources: None.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is associated with cardiac injury and stroke severity in patients after acute ischemic stroke
Authors: Mihalovic M , Mikulenka P , Linkova H , Stetkarova I , Peisker T , Lauer D , Tousek P
Published: October 2022

Background

Patients after acute stroke frequently show signs of myocardial injury. The pathophysiology and impact on patient's outcome are not fully understood. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is cytokine known to be associated with cardiovascular events.

Purpose

We aimed to assess TRAIL level dynamic changes in patients after acute ischemic stroke and its relations to cardiac injury, stroke severity and impact on short-term outcome.

Methods

Between August 2020 and August 2021, 104 consecutive patients after acute ischemic stroke (AIS) were enrolled in our study. Blood samples were obtained from patients at the time of admission, 24- and 48-hours later to determine levels of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitive Troponin I (hs-cTnI). Twelve lead ECG at admission, 24-, 48-hours later and at the release of the patients were obtained. Patients underwent echocardiographic examination within first 5 days of hospitalization, if eligible. National Institutes of Health Stroke Scale (NIHSS) at admission and modified Rankin Scale (mRS) at 90 days following the patient's discharge from the hospital were performed. Chi-square, Fishers exact test and regression analysis were performed to detect differences between variables using SPSS statistics. Results were considered statistically significant at a significance level of p<0.05.

Results

We found significant negative association between TRAIL and NT-proBNP at admission (p=0.039), after 24 (p=0.043) and 48 hours (p=0.023) of hospitalization. There was significant negative association between TRAIL and hs-cTnI at admission (p=0.04). Moreover, we found significant negative association between TRAIL and stroke severity evaluated by NIHSS at admission (p=0.044) and negative association with severe disability or death evaluated by mRS at 90 days both after 24 (p=0.0022) and 48 hours (p=0.044) of hospitalization. In ECG analysis, lower TRAIL levels were associated with the occurrence of premature ventricular extrasystoles (p=0.043), and there was a near statistically significant association with prolonged QTc interval (p=0.07). Two patients presented with new left ventricular regional wall motion abnormality.

Conclusions

Lower TRAIL levels are associated with laboratory markers of cardiac injury, stroke severity and unfavorable functional outcome in patients after acute ischemic stroke.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Charles University Research Program Cooperatio – Cardiovascular sciences
Diagnostic performance of angiography-derived index of microvascular resistance: a systematic review and pooled meta-analysis
Authors: Zhou J , Onuma Y , Kotoku N , Kageyama S , Ninomiya K , Masuda S , Yan H , Serruys P
Published: October 2022

Background

The index of microvascular resistance (IMR) is an established measurement of coronary microcirculation status. However, it has not been widely incorporated into routine practice due to need for intracoronary instrumentation (pressure wire) and hyperaemic agents. Several angiography-derived quantitative flow ratio-based indexes of microvascular resistance (angio-IMR) have been proposed rekindling the interest for the assessment and management of microvascular disease.

Purpose

To review the overall diagnostic accuracy of angio-IMR against wire based IMR.

Methods

A systematic review of the literature was performed and studies comparing angio-IMR with wire based IMR were included. Individual data was extracted using semi-automatic digitalization. Correlation of angio-IMR with IMR and its diagnostic performance against IMR were analysed.

Results

Six studies directly comparing angio-IMR with IMR were included. Data extraction rate was 85.1% (582/684 vessels). There was a linear correlation between angio-IMR and IMR (β=0.483, R square=0.298) (Figure 1A). Pooled sensitivity was 77%, specificity was 66%, positive predictive value was 65%, negative predictive value was 78%, and accuracy was 71.0%. Pooled area under receiver operator curve of angio-IMR for predicting IMR diagnosed coronary microvascular disease was 0.754 (95% confidential interval 0.715 to 0.793) (Figure 1B). Similar diagnostic performance was observed in subgroups of patients with or without ST-segment elevation myocardial infarction.

Conclusions

Currently available angio-IMR showed a clearly useful discrimination and diagnostic performance against the standard of wire based IMR.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): China Scholarship Council
The isovolumetric contraction as marker of ventricular performance in patients with afterload mismatch
Authors: Sinanis T , Markidis E , Mavroudeas S , Sideras E , Vittorakis E
Published: October 2022

Introduction

The gold standard for the evaluation of ventricular function is currently the echocardiographic measured ejection fraction (EF). However, the use of this parameter has limitations, which are more important in populations with afterload mismatch and especially when this mismatch is severe. On the other hand, the assessment of a pump function in fluid dynamics is done using the head pressure, which is product of pressure when the flow is zero. During the cardiac cycle, this situation occurs during the isovolumetric contraction.

Purpose

The aim of this study is to assess the clinical and pathophysiological importance of the isovolumentric contraction in the evaluation of the ventricular performance.

Method

110 patients with severe aortic stenosis and pulmonary arterial hypertension were investigated. The area under the curve (AUC) of the isovolumetric contraction was measured using the pressure curves of the right ventricle-pulmonary artery and left ventricle-aorta ascendens. This AUC was then correlated with the echocardiographic measured ejection fraction (EF), the stroke volume (SV) and the total ventricular work, defined as the product of pressure and flow.

Results

The AUC of the isovolumetric contraction correlates statistically significant with the ejection fraction of the corresponding ventricle (p 0.0001). Both AUC of the isovolumetric contraction and the ejection fraction showed a statistic significance with the total work of the ventricle (AUC with R2 0.49, p 0.0001, EF R2 0.51, p 0.0001). Stroke volume was significant only in the correlation with the ejection fraction. A statistic significant one sample t test could be found for the EF (decreased, p 0.001) and for the AUC of the isovolumetric contraction (increased, p 0.001) but not for the total work of the ventricle.

Conclusion

The AUC of the isovolumetric contraction correlates statistically significant with the ejection fraction and the total ventricular work but not the stroke volume in patients with afterload mismatch. Especially in these populations it demonstrates a significant increase when compared with normal values.

Funding Acknowledgement

Type of funding sources: None.
Improvement in angina pectoris after percutaneous coronary interventions in focal and diffuse coronary artery disease
Authors: Munhoz D , Collet C , Collison D , Mizukami T , McCartney P , Sonck J , Ford T , Berry C , De Bruyne B , Oldroyd K
Published: October 2022

Objective

To investigate the effect of PCI on patient-reported outcomes in focal and diffuse coronary artery disease (CAD) as defined by the pullback pressure gradient (PPG).

Background

Improvements in fractional flow reserve (FFR) following PCI are associated with freedom from angina. CAD patterns influence the FFR change after stenting. Therefore, CAD patterns might be essential to assess the likelihood of PCI success in terms of angina relief.

Methods

This is a sub-analysis of the TARGET-FFR randomized clinical trial (NCT03259815). The 7-item Seattle Angina Questionnaire (SAQ-7) and EuroQol five-level EQ-5D questionnaire (EQ-5D-5L) were administered at baseline and three months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks and the median PPG value was used to define focal and diffuse CAD.

Results

103 patients (51 with focal and 52 with diffuse disease) were analyzed. There were no differences in baseline characteristics between patients with focal and diffuse CAD. Patients with focal disease had larger increases in FFR with PCI than those with diffuse disease (0.30±0.14 units vs 0.19±0.12 units, p<0.001). Patients who underwent PCI to focal CAD had significantly higher SAQ-7 summary scores at follow-up compared to those with diffuse CAD (87.1±20.3 vs. 75.6±24.4, mean difference 11.5 [95% CI 2.8 to 20.3], p=0.01). Following PCI, residual angina was present in 39.8% of all patients but was significantly lower among those with treated focal CAD (27.5% vs 51.9%, p-value=0.020).

Conclusion

Persistent angina after PCI was almost twice as common in patients with diffuse CAD as defined by the pre-PCI PPG. Patients with focal disease reported greater improvement in angina and quality of life with PCI. The likelihood of successful angina relief from PCI can be predicted by the baseline pattern of CAD.

Funding Acknowledgement

Type of funding sources: None.
Prognostic role of discordance between plain coronary angiography and quantitative flow ratio in revascularization guidance
Authors: Oikonomou D , Terentes-Printzios D , Gkini K P , Gardikioti V , Aznaouridis K , Dima I , Tsioufis K , Vlachopoulos C
Published: October 2022

Background/Introduction

Percutaneous coronary intervention (PCI) guided by functional coronary stenosis severity has been associated with less clinical adverse events compared with plain coronary angiography. Quantitative flow ratio (QFR) has proven to be a reliable tool for functional assessment of coronary lesions.

Purpose

To investigate the prognostic role and the extend of disagreement between plain coronary angiography and QFR in guiding the decision to treat a coronary lesion.

Methods

We retrospectively performed an offline QFR analysis in consecutive patients who underwent coronary angiography in a single center. Patients with referral for coronary artery bypass graft surgery after coronary angiography were excluded. We aimed to measure QFR in all vessels of each patient. Patients were divided in two groups according to the concordance or discordance of the two methods. Patients with at least one vessel with QFR value ≥0.80 treated with PCI and/or at least one vessel with QFR value <0.80 not treated with PCI were included in the discordance group. The remaining patients formed the concordance group. Primary endpoint was the composite outcome of cardiovascular death, myocardial infraction and ischemia-driven revascularization.

Results

Overall, we included 549 patients in the study. Concordance between plain coronary angiography and QFR was present in 404 (73.6%) patients, while discordance between the two methods was found in 145 patients (26.4%). Baseline patient characteristics are displayed in Figure 1. Patients in the discordance group were older, with more extended coronary artery disease and higher SYNTAX score. After a median follow-up period of 30.5 (26.4–33.7) months, multivariate regression analysis showed significant higher rate of the composite outcome in the discordance group (OR: 2.975 95% CI 1.782–4.967, p<0.001) (Figure 2).

Conclusion

In our study, discordance between plain coronary angiography and QFR in revascularization guidance was present in approximately one fourth of patients and was found to be a strong independent predictor of higher cardiovascular adverse events.

Funding Acknowledgement

Type of funding sources: None.
Diagnostic performance of angiography-derived FFR in patients presenting with NSTE-ACS
Authors: Skalidis I , Meier D , Muller O , Fournier S
Published: October 2022

Background

Precise non-invasive methods to measure fractional flow reserve (FFR) are actively being explored, aiming to avoid the use of invasive pressure wire and the administration of hyperaemic stimulus. Coronary angiography-derived FFR (FFRangio) has already proved its diagnostic performance in validation studies in the context of stable coronary artery disease. However, its applicability in the context of non-ST-segment elevation acute coronary syndromes (NSTE-ACS) has yet to be established.

Purpose

The study sought to determine the diagnostic performance of FFRangio in patients presenting with NSTE-ACS and evaluate if it could serve as a reliable alternative to invasive FFR.

Methods

This study is a prospective, single-center, single-arm, double-blinded clinical study comparing the FFR calculated by FFRangio to invasive FFR and it represents a sub-study of a protocol evaluating the diagnostic performance of FFR-CT in NSTE-ACS patients, whose design and rationale has been previously published. Invasive FFR was measured in all angiographically intermediate lesions (30%-70% stenoses) in NSTE-ACS patients and was then compared to FFRangio which was measured in the same position, by a blinded operator. The study primary endpoints were the per lesion diagnostic characteristics of FFRangio using invasive FFR as the standard of reference. A value of ≤0.80 was considered as the threshold for a positive result (i.e. functionally significant lesion) for both invasive and FFRangio.

Results

Among the 46 NSTE-ACS patients included in the study according to the inclusion/exclusion criteria, a total of 60 vessels underwent invasive FFR measurement. The mean value of invasive FFR was 0.83±0.3 with 36% being positive. The mean FFRangio was 0.82±0.1 with 36% being positive. FFRangio showed a sensitivity of 95.5%, a specificity of 97.4% and a diagnostic accuracy of 96.7% to detect the functional significance of an angiographically intermediate stenosis. Moreover, it showed similar diagnostic performance across all three coronary arteries. FFRangio values correlated well with invasive FFR measurements (r=0.83, P<0.001) and the Bland–Altman 95% confidence limits were between −0.12 and 0.10.

Conclusions

This study adds to the limited knowledge on the validity of FFRangio in the context of acute coronary syndromes and demonstrates excellent diagnostic performance as well as strong correlation to the invasive FFR for in the setting of NSTE-ACS. It contributes to the growing body of evidence suggesting that FFRangio can precisely calculate FFR in a wide range of clinical situations thus diminishing the risks of an invasive procedure and the use of hyperaemic agent. Since it is non-invasive, simple and cost-effective, the use of FFRangio could be routinely considered to guide treatment decision in angiographically intermediate coronary lesions in the context of NSTE-ACS.

Funding Acknowledgement

Type of funding sources: None.
Side effects and major adverse cardiac events caused by fractional flow reserve measurement: a systematic review and meta-analysis of 12,215 patients
Authors: Altstidl J M , Gaede L , Troebs M , Marwan M , Achenbach S
Published: October 2022

Background

Current guidelines recommend revascularization based on fractional flow reserve (FFR) in angiographically intermediate coronary stenoses. Side effects of FFR caused by adenosine administration are usually transient with little relevance. However, major adverse cardiac events (MACE), such as coronary artery occlusion, may infrequently occur as a consequence of intracoronary wire manipulation and little is known about their incidence. This systematic review aims to analyze the rate of side effects including MACE caused by FFR measurement as reported in large multicenter studies.

Methods

A PubMed database query for “fractional flow reserve” of the type “multicenter study” identified 348 records. Subsequently, one retracted record was excluded, another record was excluded as it contained no digital object identifier, 52 records were excluded since access could not be obtained, and one was a duplicate. Of the 293 records screened, only 15 contained relevant information on adverse effects or events due to FFR measurement and had included at least 100 patients. To systematically report the frequency of adverse events, the micro average for each event type was calculated across all studies where it was described.

Results

This systematic review includes data from 15 studies with a total of 12,215 patients. Measurement of FFR was successful in 99.1% (5,163 of 5,210). Hyperemia for FFR measurement was usually induced by adenosine, in most cases administered intravenously. Adverse effects are summarized in Figure 1. With 34.5% (778 of 2,257) of patients reporting chest pain or discomfort, this was the most common side effect of adenosine administration. Dyspnea was noted by 20.0% (250 of 1,250) of patients. Heart-rhythm disturbances occurred in 3.3% (185 of 5,646) of patients. More specifically, a transient atrioventricular block was reported in 2.6% (115 of 4,396) of patients, whereas ventricular arrhythmia was considerably less frequent with 0.2% (11 of 5,864). Hypotension was described by 0.9% (14 of 1,574) of patients, vomiting or nausea by 0.9% (11 of 1,250), and bronchospasm by 0.2% (11 of 4,836). MACE were infrequent, but not negligible: the pressure wire used for FFR measurement was reported to cause coronary artery dissection in 0.2% (8 of 4,158) of patients, coronary artery occlusion in 0.2% (4 of 2,381) of patients, and coronary artery perforation in 0.1% (2 of 3,228) of patients.

Conclusions

Chest pain, dyspnea, and transient arrhythmias are commonly experienced by patients in the context of adenosine but bear limited clinical relevance. The analysis of a large patient cohort revealed that MACE caused by vessel injury, while infrequent, occur at a rate of approximately 0.5% and should hence be considered relevant.

Funding Acknowledgement

Type of funding sources: None.
Saline-induced coronary hyperemia with continuous intracoronary thermodilution is mediated by intravascular hemolysis
Authors: Bertolone D , Gallinoro E , Candreva A , Fernandez Peregrina E , Bailleul E , Meeus P , Sonck J , Bermpeis K , Esposito G , Paolisso P , Heggermont W , Adjedj J , Barbato E , Collet C , De Bruyne B
Published: October 2022

Objectives

To test whether local hemolysis is a potential mechanism of saline-induced coronary hyperemia.

Background

Absolute coronary flow can be measured by intracoronary continuous thermodilution of saline through the lateral side holes of a dedicated infusion cathete. A saline infusion rate at 15–20 mL/min induces an immediate, steady-state, maximal microvascular vasodilation. The mechanism of this hyperemic response remains unclear.

Methods

Twelve patients undergoing left and right catheterization were included. The left coronary artery and the coronary sinus were selectively cannulated. Absolute resting and hyperemic coronary flow were measured by continuous intracoronary thermodilution. Arterial and venous samples were collected from the coronary artery and the coronary sinus in five phases: baseline (BL); resting flow measurement (Rest, saline infusion at 10 mL/min); hyperemia (Hyperemia,saline infusion at 20 mL/min); post-hyperemia (Post-Hyperemia, two minutes after the cessation of saline infusion); and control phase (Control, during infusion of saline through the guide catheter at 30 mL/min).

Results

Hemolysis was visually detected only in the centrifugated venous blood samples collected during the Hyperemia phase. As compared to Rest, during Hyperemia both LDH (131.50±21.89 U/dL [Rest] and 258.33±57.40 U/dL [Hyperemia], p<0.001) and plasma free hemoglobin (PFHb, 4.92±3.82 mg/dL [Rest] and 108.42±46.58 mg/dL [Hyperemia], p<0.001) significantly increased in the coronary sinus. The percentage of hemolysis was significantly higher during the Hyperemia phase (0.04±0.02% [Rest] vs 0.89±0.34% [Hyperemia], p<0.001).

Conclusions

Saline-induced hyperemia through a dedicated intracoronary infusion catheter is associated with hemolysis. Vasodilatory compounds released locally, like ATP, are likely ultimately responsible for localized microvascular vasodilation.

Funding Acknowledgement

Type of funding sources: None.
Correlation of FFR measured after DES implantation with clinical parameters and long-term clinical outcome
Authors: Csanadi B , Fulop G , Szoke S , Szonyi T , Dekany G , Pinter T , Takacs P , Abdelkrim A , Beres A , Fontos G , Andreka P , Nyolczas N , Piroth Z
Published: October 2022

Introduction

The role of fractional flow reserve (FFR) measured directly after drug eluting stent (DES) implantation (post-PCI FFR) is not clear in predicting major adverse cardiac events (MACE), and it is not known which clinical parameters affect post-PCI FFR.

Aim

We aimed to clarify the relationship between post-PCI FFR and clinical parameters, post-PCI FFR and long-term MACE and determine the best post-PCI FFR cut-off in MACE prediction.

Method

Patients who underwent post-PCI (DES) FFR measurement at our center between March 2009 and January 2021 were included. We examined the relationship between post-PCI FFR and gender, age, hypertension, diabetes mellitus, hyperlipidemia, indication (acute (ACS) vs. chronic coronary syndrome (CCS)), stent diameter, in-stent restenosis vs de novo lesion category, proximal vs. non-proximal lesion location, LAD (vs. non-LAD) location, and pre-PCI FFR. We sought to determine the correlation between post-PCI FFR and target vessel-related MACE (cardiovascular death (CVD), non-fatal myocardial infarction (MI), recurrent revascularization (TVR)). Optimal cut-off was determined by ROC curves.

Results

Post-PCI FFR measurement was performed in 500 coronary arteries of 434 patients. LAD location (0.86 vs. non-LAD 0.91, p<0.001), male gender (0.87 vs. 0.89, p=0.001), younger age (p=0.0215), smaller stent diameter (p=0.0028) and lower pre-PCI FFR (p=0.0006) proved to be independent predictors of lower post-PCI FFR, no other parameter showed a significant correlation with post-PCI FFR. During a median follow-up of 37 months, 24 CVD, 15 MI and 47 TVR occurred. Follow-up was complete in 96.2% of patients. There was a significant inverse correlation between post-PCI FFR and MACE (p<0.001). Diabetes mellitus (p=0.0024) and in-stent restenosis (0.0356) were also independent predictors of MACE. The best post-PCI FFR cut-off for the total patient population, LAD and non-LAD lesions were 0.83 (p<0.0001), 0.83 (p<0.0001), and 0.88 (p=0.0091), respectively.

Conclusion

LAD location, male gender, younger age, smaller stent diameter and lower pre-PCI FFR value result in lower post-PCI FFR. There is no significant difference between post-PCI FFR measured in ACS vs. CCS. FFR measured after PCI, diabetes mellitus and in-stent restenosis are significant predictors of MACE-free long-term survival. The best post-PCI FFR cut-off to predict MACE was 0.83 for the whole patient population and for LAD and 0.88 for non-LAD lesions.

Funding Acknowledgement

Type of funding sources: None.
Comparison of outcomes between a single long stent and overlapping stents in long coronary artery lesion: a meta-analysis of the current literature
Authors: Saylik F , Cinar T , Selcuk M , Cicek V , Hayiroglu M I , Orhan A L
Published: October 2022

Background

There is no consensus for the treatment of diffuse coronary artery lesions with a single long stent (SLS) or with overlapping of two or more stents (OLS). In this review, we aimed to compare the outcomes between these two approaches by performing a meta-analysis based on the literature.

Methods

We searched MEDLINE, Scopus, EMBASE, Google Scholar, and the Cochrane Library for eligible studies. In total, 12 studies (n=6414) that included the outcomes in the follow-up period were included in this meta-analysis.

Results

Patients with OLS had higher risk of cardiac death and target lesion revascularization (TLR) than those with SLS (RR: 1.51, confidence interval: 1.03–2.21, p=0.03, I2=0% and RR: 1.64, confidence interval: 1.02–2.65, p=0.04, I2=38%, respectively). Fluoroscopy time was prolonged in OLS group compared to SLS group (SMD: 0.35, confidence interval: 0.25–0.46, p<0.01, I2=0%). Contrast volume usage was higher in the OLS group, but there was significant heterogeneity in pooled analysis (I2=95%). In subgroup analysis, there were no differences with respect to outcomes between the studies reported before and after the year 2015.

Conclusion

This was the first meta-analysis to indicate that cardiac death and TLR were higher and fluoroscopy time was longer in the OLS group than in the SLS group.

Funding Acknowledgement

Type of funding sources: None.
Association of body mass index with long-term outcomes after elective and semi-urgent percutaneous coronary intervention
Authors: Ho J S Y , Soh R Y H , Djohan A H , Sim H W , Loh P H , Yeo T C , Tan H C , Chan M Y , Sia C H
Published: October 2022

Background

While obesity is associated with cardiovascular mortality and morbidity, patients with higher body mass index (BMI) may have better outcomes post-percutaneous coronary intervention (PCI). This “obesity paradox” is controversial and needs clarification.

Purpose

We aimed to investigate the relationship between BMI and outcomes post-PCI in an Asian cohort.

Methods

A retrospective cohort study was performed on consecutive patients who underwent semi-urgent PCI for non-ST elevation myocardial infraction or unstable angina, and elective PCI for stable angina from January 2014 to December 2015 in a tertiary centre. Patients were underweight (BMI <18.5), normal weight (BMI 18.5–22.9), overweight (BMI 23–24.9), pre-obese (BMI 25–29.9) or obese (BMI ≥30), according to the WHO Asian classification. The primary endpoint was all-cause mortality. The secondary outcomes were subsequent events of stroke or transient ischemic attack, myocardial infarction (MI) and congestive cardiac failure (CCF).

Results

1,610 patients were followed up for 3.71 (±0.97) years, 19.7% were female and mean age was 62.1 years (Table 1). BMI showed a U-shaped relationship with the incidence of death (p<0.001), MI (p=0.005), and CCF (p<0.001) (Figure 1A), which was also shown on Kaplan Meier analysis (Figures 1B-E). With reference to normal weight patients on multivariable Cox analysis, overweight (adjusted HR 0.64, 95% CI 0.42–0.97) and pre-obese (adjusted HR 0.55, 95% CI 0.38–0.80) patients had lower mortality. Underweight patients had higher risk (adjusted HR 2.12, 95% CI 1.01–4.46), while pre-obese patients had lower risk of MI (adjusted HR 0.56, 95% CI 0.34–0.92) compared to normal weight patients. Underweight and obese patients had higher risk of CCF (underweight: adjusted HR 3.05, 95% CI 1.45–6.42; obese: adjusted HR 1.86, 95% CI 1.03–3.35) compared to normal weight patients.

Conclusion

Patients at the lower and upper extremes of BMI demonstrated higher risk of mortality, MI and CCF post-PCI.

Funding Acknowledgement

Type of funding sources: None.
Angiographic derived physiological assessment after intervention for predicting 2-year vessel-oriented composite endpoints in Multivessel TALENT trial
Authors: Kageyama S , Serruys P W , Masuda S , Ninomiya K , Kotoku N , Onuma Y
Published: October 2022

Aims

The purpose of the study is to assess the treatment results in the first 200 patients in the ongoing Multivessel TALENT trial and to predict the vessel-oriented endpoint by assessing the quantitative flow ratio (QFR) post PCI in a central independent core laboratory.

Methods

In this prospective, randomized, 1:1 balanced, multi-centre, open-label trial, de novo multivessel coronary artery disease patients without left main disease are assigned to the sirolimus-eluting stent or everolimus-eluting stent arm. The percutaneous coronary intervention (PCI) is planned based on functional lesion evaluation by QFR provided by the Core laboratory and the PCI has to be optimized by intravascular imaging, optimal pharmacological treatment and prasugrel monotherapy.

Results

Mean age of the population was 66.6±14.7 years, and 78.1% of them were male. This population consists of 17.4% unstable angina and of 31.8% diabetic patients. Anatomical SYNTAX score was 18.8±9.1. Total 458 lesions were treated from September 2020 to December 2021. Left anterior descending artery accounts for 40.3%, bifurcation lesion was present in 40.8%, total occlusion in 4.2%. The average stent diameter and total stent length were 3.0±0.4mm and 38.7±22.4mm, respectively. Intravascular imaging was used in 92.8% of treated vessels (intravascular ultrasound 56.5%, optical coherent tomography 36.3%). Pre-PCI QFR was analysable in 435 vessels (0.59±0.21), and 5.5% of them were treated even though the pre-PCI QFR values were more than 0.8. Post-PCI QFR has been so far analysed in 303 vessels (0.93±0.11) and 79.5% of them achieved a post-PCI QFR equal or superior to 0.91. Based on the previous study [1], Two-year vessel-oriented composite endpoint (VOCE) was estimated to become 5.4% in the present study population (3.7% in the patient group that achieved post PCI QFR equal or superior to 0.91, while 12% in the patients who could not reach the threshold), which was almost equal to what is expected in the power calculation.

Conclusions

In the Multivessel TALENT trial, the large majority of the vessels treated (94.5%) complied with the hemodynamic criteria of recommended PCI as provided by the QFRs of the Core laboratory. Favourable post-PCI QFR (≥0.91) obtained in 80% of the patients let expected a favourable VOCE outcome of 5.4%.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): The National University of Ireland Galway