bluuebunny/crossref_metadata_2025 huggingface dataset:
Supra-normal values of resting left ventricular systolic function are associated with decreased survival: to good to be normal?
Authors: C De A Bellagamba C , Ciampi Q , Bombardini T , Cortigiani L , Zagatina A , Wierzbowska-Drabik K , Kasprzak J D , Amor M , Djordjevic-Dikic A , Boshchenko A , Rodriguez Zanella H , Gaibazzi N , Pepi M , Picano E
Published: October 2022

Background

Hyper-contractile phenotype of the left ventricle (LV) is generally considered prognostically benign, but recent data challenge this intuitive assumption.

Aim

To assess the effects of resting LV function on survival.

Methods

In a prospective, observational, multicenter study, we recruited 5,122 patients (age 65±11.1 years, 2974 males, 58%) with chronic coronary syndromes referred for resting transthoracic echocardiography with technically successful volumetric echocardiography in 14 accredited laboratories. All recruiting centers had a structured follow-up program with >90% follow-up rate. In each patient, we quantitatively assessed (by Simpson's biplane, apical single-plane or parasternal linear method) LV end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF). As a load-independent index of LV contractility, LV force was estimated as systolic blood pressure by cuff sphygmomanometer/ESV. All-cause death was the only considered outcome end-point.

Results

EF was 59±11% (normal reference sextile = 58.0–59.9%). Force was 4.51±2.11 mmHg/ml (normal reference sextile = 3.50–4.27 mmHg/ml). The correlation between EF and force was linear (r=0.585, p<0.001). After a median follow-up of 862 days, there were 265 all-cause deaths. Considering EF values, mortality was lowest in the highest sextile (>67%) and significantly higher in the lowest sextile (EF <52%): see figure, left panel. A U-shaped curve was found with force, with mortality values being lowest in the middle sextile and significantly higher in the lowest sextile (<2.59 mmHg/ml) and in the highest sextile (>6.36 mmHg/ml): see figure, right panel. At multivariable analysis, after adjustment for age, diabetes, EF, and prior myocardial infarction, both the highest sextile of force (HR 1.84, 95%, confidence intervals 1.12–3.03 p=0.015), and the lowest sextile of force (HR 1.77, 95%, confidence intervals 1.08–2.90 p=0.024) were associated with decreased survival.

Conclusion

Sub-normal values of resting ejection fraction and super- and sub-normal values of the force are associated with worse survival in patients with chronic coronary syndromes. This U-shaped curve of mortality is detectable only with the force, a load independent index of LV contractility: too much of a good thing such as LV contractility can be dangerous on the long-run.

Funding Acknowledgement

Type of funding sources: None.
Transcription factor 21 and prognosis in a coronary population
Authors: Santos M , Mendonca M I , Temtem M , Sa D , Sousa A C , Freitas S , Rodrigues M , Henriques E , Borges S , Guerra G , Freitas A I , Ornelas I , Drumond A , Palma Dos Reis R
Published: October 2022

Introduction

TCF21 is a member of the basic helix-loop-helix (bHLH) transcriptor factor family, being critical for embryogenesis of the heart. It regulates epicardium-derived cells differentiation into smooth muscle (SMC) and fibroblast lineages. The biological roles of TCF21 in epicardial fate determination and the progression of atherosclerosis remains a controversial issue.

Purpose

Investigate the impact of the TCF21 rs12190287 G>C variant on the prognosis of a coronary artery disease (CAD) cohort.

Methods

A prospective study was performed with 1,713 CAD patients (mean age 53.3±7.8; 78.7% male) surveyed in terms of MACE occurrence in an extended follow-up of 5.0±4.3. TCF21 rs12190287 was genotyped and analysed using the dominant model (GC+CC) and, subsequently, compared with the wild-type GG to evaluate the survival probability by Kaplan-Meier. A Cox regression analysis with all the risk factors and genetic models was performed to assess the independent variables associated with the prognosis of CAD patients.

Results

GG wild genotype was present in 9.5% of the population, GC in 43.2% and the risk genotype CC accounted for 47.3% of the CAD patients. The dominant model GC+CC showed a worse survival throughout the follow-up period. After multivariate Cox regression analysis, this model remained in the equation as an independent risk factor for MACE occurrence with an HR of 1.41 (p=0.033) together with multivessel disease, physical inactivity, chronic kidney disease (CKD) and diabetes.

Conclusion

TCF21 rs12190287 is a risk factor for prognosis in our population. The role of this gene may influence fundamental SMC processes in response to vascular stress, accelerating atherosclerosis progression and may represent a target for future therapies.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM
Lipoprotein(a) and cardiovascular outcomes in patients with coronary artery disease and impaired glucose metabolism
Authors: Sa D , Palma Dos Reis R , Santos M , Temtem M , Sousa A C , Henriques E , Rodrigues M , Freitas S , Borges S , Ornelas I , Drumond A , Mendonca M I
Published: October 2022

Introduction

Lipoprotein(a) [Lp(a)] is an LDL-like molecule composed of a part of apolipoprotein(a) bounding covalently to apolipoprotein B-100. High plasma Lp(a) levels were associated with MACE in stable CAD patients. Recent research shows contradictory results in stable CAD patients with high Lp(a) plasmatic levels and impaired glucose metabolism in MACE occurrence.

Purpose

Investigate whether high Lp(a) levels were associated with MACE in CAD patients with impaired glucose metabolism, at an extended follow-up.

Methods

A prospective cohort of 1,127 CAD patients with impaired glucose metabolism (pre-diabetes and diabetes) was observed during 4.9±3.4 years. Pre-diabetes was considered when fasting plasma glucose ranged from 5.6 to 6.9 mmol/L, or hemoglobin A1c levels ranging from 5.7 to 6.4%. Lp(a) levels ≥30 mg/dL were considered high. Bivariate and multivariate Cox regression analysis evaluated the risk of Lp(a) ≥30 mg/dL for MACE occurrence. Kaplan-Meier curves estimated the survival probability for high and low Lp(a) levels.

Results

Of the patients with Lp(a) levels ≥30, 44.4% presented MACE and 32.0% had no MACE (p<0.0001). Cox regression analysis with smoking, hypertension, dyslipidemia, physical inactivity and kidney failure (creatinine clearance <60 mL/min) showed that high Lp(a) remained in the equation as an independent risk factor for MACE (HR=1.24; p=0.031). The Kaplan-Meier showed, at 10-year' follow-up, a better survival in the group with lower Lp(a) levels (p=0.023).

Conclusion

Our study demonstrated that high Lp(a) levels were an independent predictor of MACE and cardiovascular mortality in a CAD population with impaired glucose metabolism. Lp(a) measurement may help further risk stratification for diabetes and pre-diabetes patients suffering CAD. With the recent development of drugs that selectively lower Lp(a) levels, this marker can become a clinical target for reducing CVD risk.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM
The incremental value of exercise ECG to myocardial perfusion SPECT for prediction of cardiac events
Authors: Kraen M , Akil S , Heden B , Berg J , Ostenfeld E , Carlsson M , Arheden H , Engblom H
Published: October 2022

Background

Both myocardial perfusion SPECT (MPS) and exercise ECG (Ex-ECG) are known to carry prognostic information in patients with chronic coronary syndrome (CCS). However, it is not fully understood if combining MPS and Ex-ECG results improves risk prediction. Current guidelines no longer recommend Ex-ECG for diagnostic evaluation of CCS, but adding Ex-ECG results to MPS could be of incremental prognostic importance.

Purpose

The study aimed to assess the incremental prognostic value of Ex-ECG to MPS results in patients with CCS.

Methods

A single-center study of 908 consecutive patients with CCS (age 63±9 years, 49% male) who underwent a MPS with Ex-ECG. Subjects were followed for five years. The clinical endpoint was a composite of cardiovascular death (CV), acute myocardial infarction (AMI), unstable angina and unplanned PCI. National registry data and electronic medical charts were used for end point allocation.

Results

Combining the findings of MPS and Ex-ECG resulted in concordant evidence of ischemia in 72 patients (8%) or absence of ischemia in 634 patients (70%). Dis-concordant results were found in 202 patients (22%; MPS−/Ex-ECG+, n=126 and MPS+/Ex-ECG−, n=76). During follow-up 95 composite cardiac events occurred (CV deaths n=6, AMI n=27, unstable angina n=34 and unplanned PCI n=28). Kaplan-Meier curves display an increased risk of cardiac events in patients with any combination of abnormal stress test results (Figure 1). In a multivariable regression model (adjusting for age, sex, smoking, known IHD, diabetes, dyslipidaemia and exercise capacity) MPS was the strongest predictor of cardiac events regardless of Ex-ECG results (MPS+/Ex-ECG−, Hazard ratio (HR) = 3.0, p=0.001 or MPS+/Ex-ECG+, HR=4.0, p<0.001). However, an abnormal Ex-ECG almost doubled the risk of event in subjects with a normal MPS (MPS−/Ex-ECG+, HR=1.9, p=0.04).

Conclusions

Combining the results from MPS and Ex-ECG in patients with chronic coronary syndrome lead to an improved prediction of future cardiac events. Even though MPS is the stronger predictor, there is an incremental prognostic value of adding data from Ex-ECG to MPS, especially in patients with normal MPS findings.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Swedish Heart and Lung Foundation, Region of Scania
Acute myocardial infarction and work inability: insights from the AMIS Plus registry
Authors: Barresi F , Foster-Witassek F , Rickli H , Pedrazzini G , Roffi M , Puhan M , Dressel H , Radovanovic D
Published: October 2022

Introduction

The impact of acute myocardial infarction (AMI) on the ability to pursue professional life is not well defined. Using a nationwide database, we aimed to describe the ability to return to work after AMI in Switzerland and identify factors associated therewith.

Methods

AMI patients of working-age enrolled in the AMIS Plus registry between 01/2006 and 09/2020 with data on self-reported work status before and 12 months after AMI were included. Using the Kruskal-Wallis rank sum test or Fisher's exact test we compared patient characteristics between those who did not reduce work hours, those who reduced, and those no longer working 12 months after the AMI.

Results

Of 4315 AMI patients (median (IQR) age 54 (49, 59)), 3204 (74.3%) did not reduce work, 592 (13.7%) reduced and 519 (12.0%) stopped working. Patients not reducing were youngest (median age (IQR)): 54y (49y, 58y), those who reduced: 56y (51y, 60y), those who stopped: 56y (51y, 61y), p<0.001) and more often men (no reduction: 90%, reduced: 80%, stopped: 82%, p<0.001). Patients who reduced showed worst cardiac function at AMI reflected in the highest rates of Killip class>2 (no reduction: 1.8%, reduced: 5.2%, stopped: 3.3%, p<0.001) and resuscitation before admission (no reduction: 4.1%, reduced: 6.9%, stopped: 4.0%, p=0.008). Patients who stopped work had the most comorbidities such as past AMI (no reduction: 8.6%, reduced: 10%, stopped: 13%, p=0.003), hypertension (no reduction: 45%, reduced: 50%, stopped: 54%, p<0.001), diabetes (no reduction: 10%, reduced: 13%, stopped: 16%, p<0.001) and cerebrovascular disease (no reduction: 0.8%, reduced: 1.2%, stopped: 2.3%, p=0.007). There was no significant difference for rehabilitation participation during follow up (no reduction: 84%, reduced: 86%, stopped: 84%, n.s. for all group comparisons). Multivariable regression showed that the reduction group had a higher proportion of women (OR 2.30; 95% CI 1.80–2.93 p<0.001) and were more likely to have a Killip class >2 at admission (OR 2.58; 95% CI 1.54–4.31 p<0.001) as compared to the no reduction group whereas the comparison between no reduction and work stop identified comorbidities (past MI (OR 1.46; 95% CI 1.07–1.94 p=0.016), diabetes (OR 1.59; 95% CI 1.21–2.09 p=0.001), cerebrovascular disease (OR 2.53; 95% CI 1.22–5.25 p=0.013)) and being female (OR 1.98; 95% CI 1.51–2.58 p<0.001) as major predictors for work stop.

Conclusion

Our data showed that 1:7 had reduced and 1:8 stopped professional activity 1 year after AMI. Younger age, being male and lower rates of comorbidities such as a past AMI, hypertension, diabetes and cerebrovascular disease were important factors associated with returning to work after AMI. Work reduction was significantly related with worse cardiac function whereas work stop was more related with comorbidities.

Funding Acknowledgement

Type of funding sources: None.
Association between high sensitivity C-reactive protein and coronary atherosclerosis in a general middle-aged population
Authors: Cederstrom S , Lundman P , Alfredsson J , Hagstrom E , Ravn-Fischer A , Soderberg S , Yndigegn T , Tornvall P , Jernberg T
Published: October 2022

Background

Despite abundant knowledge about the relationship between inflammation and coronary artery disease (CAD), it is still unknown whether high sensitivity C-reactive protein (hsCRP) is associated with coronary atherosclerosis in the general population.

Objectives

The project aimed to study the association between systemic inflammation, measured as hsCRP, and coronary artery atherosclerosis in a large population based cohort.

Methods

30,154 randomly selected men and women aged between 50 and 64 years were included in the SCAPIS (Swedish Cardiopulmonary Bioimage Study). After excluding those not undergoing coronary computed tomography angiography (CCTA), those with proximal segments not technically assessable and those with missing values of hsCRP, 25,408 individuals were analysed. Coronary artery atherosclerosis was defined as presence of plaque of any degree (1–49% or ≥50% diameter stenosis) or segments not assessable due to calcification in any of the 18 coronary segments. Analysis of severe atherosclerosis included participants with ≥50% diameter stenosis in any of the left main coronary artery (LMCA), the proximal left anterior descending artery (LAD) or three vessel disease including ≥50% diameter stenosis in any of the segments in each of the LAD, right coronary artery (RCA) and circumflex artery (CX). Participants with hsCRP above the lowest detection limit (≥0.7mg/L) were divided into tertiles and compared with hsCRP<0.7 mg/L as a reference.

Results

The highest tertile of measurable hsCRP (≥2.3 mg/L) was associated with coronary atherosclerosis in a multivariate analysis adjusted for classical cardiovascular risk factors (Table 1). HsCRP was also related to atherosclerosis with significant coronary artery diameter stenosis ≥50%, ≥4 segments involved, severe atherosclerosis and atherosclerosis with noncalcified plaques. Also, moderately elevated hsCRP (1.2–2.2 mg/L) was significant associated with noncalcified plaques. In a stratified analysis, coronary atherosclerosis was associated with the two highest tertiles of hsCRP (≥1.2 mg/L) in women, but not in men.

Conclusion

Elevated hsCRP was associated with the prevalence of coronary atherosclerosis in a population based cohort of middle-aged men and women. The relationships were more pronounced for atherosclerosis with noncalcified plaques and in women compared to men. This suggests that more attention should be given to hsCRP in risk assessment in middle-aged individuals without known disease, especially in women.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): The Swedish Heart Lung FoundationKnut and Alice Wallenberg Foundation
Impact of in-hospital medical management for COVID-19 pandemic on door-to-balloon time in patients with ST-elevation myocardial infarction
Authors: Takasaki A , Kurita T , Yanagisawa M , Ino A , Hiramatsu D , Ikmi A , Ito H , Kato T , Fukuoka S , Sugimoto T , Nakata T , Masuda J , Tanabe M , Kakimoto H , Dohi K
Published: October 2022

Background

Delayed door-to-balloon (DTB) time and deterioration of in-hospital mortality during the coronavirus disease 2019 (COVID-19) pandemic have been reported. Little is known about the impact of changes in in-hospital medical management before primary percutaneous coronary intervention (PCI) for COVID-19 such as screening test (antigen or polymerase chain reaction (PCR) tests, chest CT for excluding the pneumoniae) and primary PCI under full personal protective equipment (PPE) on DTB time and in-hospital mortality.

Purpose

The purpose of this study was to evaluate the impact of in-hospital medical management for COVID-19 on DTB time and in-hospital mortality during COVID-19 pandemic period.

Methods

We compared DTB time and in-hospital mortality of 502 ST-elevation myocardial infarction (STEMI) patients during COVID-19 pandemic (February 2020 and January 2021) with 2035 STEMI patients before pandemic (February 2016 and January 2020) using date from Mie ACS registry, a retrospective and multicenter registry.

Results

The COVID-19 screening tests before primary PCI and/or primary PCI under full PPE was performed on 173/502 (34.5%) patients (antigen or PCR tests; 39 (7.8%), chest CT; 156 (31.3%), full PPE; 11 (2.2%)). These patients had lower rate of achievement of DTB time ≤90 min compared with others (Figure 1A). Moreover, In-hospital management of COVID-19 screening tests and/or primary PCI under full PPE was an independent factor of DTB time>90 min with odds ratio of 1.94 (95% confidential interval: 1.37–2.76, p<0.001). In addition, in-hospital mortality of those patients was higher compared with others (Figure 1B).

Conclusion

In-hospital medical management for COVID-19 screening tests before primary PCI and/or primary PCI under full PPE was the independent factor of DTB time>90 min. This study reinforces the need to focus efforts on shortening DTB time, while controlling the epidemic of infection.

Funding Acknowledgement

Type of funding sources: None.
Low-density lipoprotein cholesterol levels and long-term bleeding in patients undergoing percutaneous coronary intervention: 5-year outcomes from a large cohort study
Authors: Li J , Li Y , Zhu P , Yang W , Yang Y , Gao R , Yuan J , Zhao X
Published: October 2022

Aims

Recent research reported that lower low-density lipoprotein cholesterol (LDL-C) is associated with more in-hospital bleeding in acute coronary syndrome (ACS) patients. However, the association between lower LDL-C levels and long-term bleeding in percutaneous coronary intervention (PCI) patients remains unclear.

Methods

A total of 10724 patients treated with PCI enrolled in ourhospital from January 2013 to December 2013. The primary endpoint was the Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding at 5 years. The secondary endpoint was intracranial hemorrhage. Taking the LDL-C value of 1.8 mmol/L (70 mg/dL) or 1.4 mmol/L (55 mg/dL) as cut-off points, patients were grouped to analyse, respectively.

Results

Among 9697 PCI patients treated with dual antiplatelet therapy finally enrolled, a total of 411 BARC type 2, 3 or 5 bleedings and 42 intracranial hemorrhage were recorded during a follow-up of 5 years. With LDL-C value of 1.8 mmol/L as cut-off point, multivariate Cox regression showed that lower LDL-C level was not associated with the risk for bleeding [hazard ratio (HR): 1.166, 95% confidence interval (CI): 0.879–1.549]. The result was consistent (HR: 1.185; 95% CI: 0.713–1.968) in a 1:4 propensity-score matching cohort (n=1285). For further study, we performed subgroup analysis which showed that lower LDL-C was not associated with the risk for bleeding in ACS (HR: 1.140; 95% CI: 0.846–1.535) or non-ACS patients (HR: 1.284; 95% CI: 0.909–1.813). With LDL-C value of 1.4 mmol/L as cut-off point, Cox regression showed that lower LDL-C level was not associated with the risk for bleeding in total population, ACS or non-ACS patients (P>0.05). The result was consistent in a 1:4 propensity-score matching cohort (n=760) (P>0.05). As for secondary endpoint, lower LDL-C level was not associated with the risk for intracranial hemorrhage whether the LDL-C value is 1.8 or 1.4 mmol/L as the cut-off point (P>0.05).

Conclusions

To the best of our knowledge, we firstly report lower LDL-C level (whether the LDL-C value is 1.8 or 1.4 mmol/L as the cut-off point) was not the independent risk factor of long-term bleeding in PCI population and ACS or non-ACS subgroup populations.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): CAMS Innovation Fund for Medical Sciences (CIFMS); Young and middle-aged talents in the XPCC Science and Technology Project
Very long-term outcomes after acute myocardial infarction in young men and women
Authors: Weizman O , Tea V , Puymirat E , Eltchaninoff H , Cayla G , Ferrieres J , Schiele F , Simon T , Danchin N
Published: October 2022

Aims

There is a paucity of data on very long-term outcomes in young women and men experiencing acute myocardial infarction (AMI).

Methods and results

The FAST-MI program consists of three nationwide French surveys carried out 5 years apart from 2005 to 2015, including consecutive AMI patients over a 1-month period with up to 10-year follow-up. The present analysis focused on adults ≤50 yo according to their gender. Women accounted for 17.5% (N=335) of the 1912 patients under 50 yo and were as old as men (43.9±5.5 vs. 43.9±5.1yo, p=0.92). Non-significant coronary artery disease was more frequent in women (12.8% vs. 5.8%, P<0.001). Women with significant coronary artery disease underwent less percutaneous coronary internvention (PCI) than men (85.9% vs. 91.3%, p=0.005), though primary PCI in ST-elevated myocardial infarction was as frequent in women (67.3% vs. 66.8%). Recommended secondary prevention medications were less prescribed at discharge in women (40.6% vs. 52.8%, p<0.001), a trend that persisted in 2015 (59.1% vs. 72.8% in 2015, p<0.001). Still, ten-year survival was similar in men (90.5%) and women (92.6%) (crude HR 0.87 [95% CI 0.55–1.57], adjusted HR 0.77 [95% CI 0.48–1.23], p=0.27) even among hospital survivors (adjusted HR 0.64 [95% CI 0.32–1.30], p=0.22). Ten-year survival was similar in patients with myocardial infarction with non-obstructive coronary arteries compared with those with significant coronary artery disease (91.8% vs. 91.0%, P=0.46)), both among men (91.6% vs. 90.7%) and women (92.9% vs. 93.0%). However, when taking into account early revascularization and discharge medications, in patients with significant coronary artery disease, adjusted 10-year mortality was significantly lower in women (HR 0.53, 95% CI 0.29–0.96, P=0.04).

Conclusions

Ten-year survival in young women with AMI is similar to that of men. However, in those with significant coronary artery disease, improving secondary prevention in women should result in better long-term outcome.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): French Society of Cardiology
Level of vascular inflammation is higher in acute coronary syndromes compared to chronic coronary disease
Authors: Araki M , Sugiyama T , Nakajima A , Yonetsu T , Seegers L M , Dey D , Lee H , McNulty I , Yasui Y , Teng Y , Nagamine T , Kakuta T , Jang I K
Published: October 2022

Background

Vascular inflammation has been recognized as one of the key factors in the pathogenesis of acute coronary syndromes (ACS). Peri-coronary adipose tissue (PCAT) attenuation by computed tomography angiography (CTA) has emerged as a marker specific for coronary artery inflammation. We examined the relationship between clinical presentation and coronary artery inflammation assessed by PCAT attenuation and coronary plaque characteristics.

Methods

Patients with ACS or stable angina pectoris (SAP) who underwent pre-intervention coronary CTA and optical coherence tomography (OCT) were enrolled. PCAT attenuation was measured around the culprit lesion and in the proximal 40 mm of all coronary arteries. PCAT attenuation and OCT findings were compared between patients with ACS versus SAP.

Results

Among 471 patients (ACS: 198, SAP: 273), PCAT attenuation was higher in ACS patients than in SAP patients both at the culprit plaque level (−67.5±9.6 Hounsfield unit [HU] vs. −71.5±11.0 HU, p<0.001) and the culprit vessel level (−68.3±7.7 HU vs. −71.1±7.9 HU, p<0.001). The mean PCAT attenuation of all 3 coronary arteries was also significantly higher in ACS patients than in SAP patients (−68.8±6.3 HU vs. −70.5±7.1 HU, p=0.007). After adjusting patient characteristics, not only thin-cap fibroatheroma (OR: 2.44; 95% CI: 1.63–3.65) and macrophages (OR: 2.07; 95% CI: 1.34–3.21) but also PCAT attenuation in the culprit plaque (OR: 1.04; 95% CI: 1.02–1.06) was associated with the clinical presentation of ACS.

Conclusions

PCAT attenuation at culprit plaque, culprit vessel, and pan-coronary levels was higher in ACS patients than in SAP patients. Vascular inflammation appears to play a crucial role in the development of ACS.

Funding Acknowledgement

Type of funding sources: None.
Prevalence and culprit lesion plaque characteristics on optical coherence tomography in patients with non-st-segment elevation acute coronary syndrome with zero coronary calcification on coronary CTA
Authors: Nagamine T , Masahiro H , Sayama K , Matsuda K , Ueno H , Misawa T , Hada M , Sugiyama T , Yonetsu T , Sasano T , Kakuta T
Published: October 2022

Background

CAC evaluated by non-contrast computed tomography is a marker of atherosclerosis. However, the characteristic features of CCTA and optical coherence tomography (OCT) of culprit lesions in patients with NSTE-ACS showing zero CAC remain unknown.

Objectives

This study aimed to assess the prevalence and characteristic features of culprit lesions on coronary CT angiography (CCTA) and optical coherence tomography (OCT) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) showing zero coronary artery calcium (CAC).

Methods

A total of 176 consecutive patients with NSTE-ACS who underwent preprocedural CCTA and OCT were studied. Patients were divided into two groups according to their CAC (zero-CAC and non-zero-CAC groups). Baseline characteristics, CCTA and OCT findings were compared between these two groups.

Results

The prevalence of patients with zero-CACS was 15.9% (28/176). Patients in zero CAC group were younger (mean age, 55 vs. 65 years, P<0.001) and had a lower prevalence of diabetes (10.7 vs 37.2%, P=0.012) than non-zero CAC group. In zero CAC group, the lower prevalence of napkin ring sign (3.5% vs. 28.4%, P=0.028), smaller LV mass index (77.7 vs. 83.9, P=0.04), lower prevalence on spotty calcification (0 vs. 83.8%, P<0.001), lower epicardial fat volume (111.3 vs. 142.6 cm3, P=0.025), and lower pericoronary adipose tissue attenuation (−71.5 vs. −70.2 HU, P=0.07) on CCTA were observed. On OCT, the frequency of plaque erosion (82.1 vs. 44.6%, P<0.001) was significantly higher in zero-CACS group. The prevalence of lipid-rich plaque (46.4 vs. 86.5%, P<0.001), thin-cap fibroatheroma (17.9 vs. 46%, P=0.006), macrophage accumulation (46.4 vs. 81.8%, P<0.001) and cholesterol crystal (7 vs. 41.9%, P<0.001) were all significantly lower in zero-CAC group.

Conclusions

Zero CAC NSTE-ACS was not rare. Zero-CAC NSTE-ACS was characterized by specific phenotypes defined by the combined assessment of CCTA and OCT. Further studies are warranted if these characteristics of NSTE-ACS on preprocedural imaging studies provide prognostic information or guidance of a specific therapeutic approach.

Funding Acknowledgement

Type of funding sources: None.
Effects of mask-wearing on treadmill exercise test
Authors: Ko S L , Tsao T P , Fong M C , Yin W H , Chang H Y
Published: October 2022

Background

Concerning about the spread of COVID-19, World Health Organization recommends wearing facemasks to minimize viral transmission. Patients are required to wear facemasks while conducting treadmill exercise tests in hospitals. The effects of mask-wearing on the results of stress exercise testing remain uncertain.

Purpose

This study aims to assess the impact of mask-wearing on the physiological parameters during treadmill exercise testing.

Methods

Patients who underwent treadmill exercise test using the Bruce protocol for the diagnosis of ischemic heart disease were retrospectively examined between 2020 and 2021. A propensity score matching was performed to adjust the baseline characteristics of patients with and without mask. Blood pressure, heart rate, exercise duration, and the interpretation of stress test were compared. The ischemic ST-segment response was defined as flat or downsloping depression of the ST seg-ment >0.1 mV below baseline and lasting longer than 0.08 second. Nondiagnostic result of treadmill exercise test was defined as absence of ischemic ST-segment response in which the 90% of maximal predicted heart rate for age and sex was not achieved.

Results

Following 1:1 propensity score matching, a total of 3,996 patients were enrolled for analysis, including 1,998 patients who performed treadmill exercise testing with masks, and 1,998 without masks. Baseline characteristics were similar between the two groups (mean age, 56.1±12.1 years; 38.7% female; mean body mass index, 25.5±3.9 kg/m2). At baseline, patients with masks had significantly higher heart rate (84.8±14.7 bpm vs. 82.5±14.0 bpm; p<0.001) and lower systolic blood pressure (130.4±19.0 mmHg vs. 132.4±18.7 mmHg; p=0.001) than those without masks. Patients with masks conducted significantly shorter duration of exercise (435±128 seconds vs. 481±133 seconds; p<0.001), achieved significantly lower measurement of peak heart rate (149.5±17.1 bpm vs. 152.7±17.0 bpm; p<0.001), and had significantly lower rate-pressure products (26,366±5,207 mmHg·bpm vs. 27,629±5,242 mmHg*bpm; p<0.001) than those without masks. The proportion of patients who were unable to complete stage II of the Bruce protocol was significantly higher among patients with masks (15.1% vs. 9.0%; p<0.001). The proportion of nondiagnostic result was significantly higher among patients with mask (12.2% vs. 8.8%; p<0.001), whereas the proportion of positive ischemic ST-segment response rate was significantly higher among patients without mask (28.1% vs. 23.3%; p=0.001).

Conclusions

Our study demonstrated that performing treadmill exercise test with mask could significantly decrease the duration of exercise, reduce the maximal achieved heart rate, decease the rate-pressure product, and thus reduce the diagnostic power of treadmill exercise testing.

Funding Acknowledgement

Type of funding sources: None.
Left atrial reservoir strain is an independent prognostic predictor in patients undergoing percutaneous mitral valve repair
Authors: Galli E , Hubert P , Vely M , Donal E
Published: October 2022

Background

Left atrial reservoir strain (LARS) is a well known prognostic predictor in several cardiac disease. Aim of the study was to assess the value of LARS in predicting the occurrence of major adverse cardiovascular events in patients undergoing percutaneous mitral valve repair (PMVR)

Methods and results

112 patients (62 males, mean age 74 years) undergoing PMVR for severe primary (n=71, 63%) or secondary MR were retrospectively included in the study. All patients underwent a comprehensive echocardiography before the procedure. Thirty-eight MACES occurred during a median follow up of 18 months. At multivariable Cox regression analysis, ischemic cardiomyopathy (CAD) [HR: 2.41 (1.11–5.24) p=0.02], indexed left atrial volume (LAVi) [HR: 1.01 (1.00–1.01) p=0 03] and LARS [HR: 0.93, (0.88–0.99) p=0.03] were all significant predictors of MACEs (Table 1). A cut-off of 13 for LARS (AUC 0 66 p=0.008 was able to predict MACEs with a 71% sensitivity and 41% specificity (Figure 1A). At Kaplan Meier analysis a PLAS <13% was associated with a worse prognosis (Log rank p=0.01) (Figure 1B).

Conclusions

LARS is an independent predictor of MACEs in patients undergoing percutaneous mitral valve repair, independently of the etiology of mitral regurgitation.

Funding Acknowledgement

Type of funding sources: None.
INOCA affects more than the coronaries
Authors: Mailey J , Moore J S , Brennan P F , Jing M , Awuah A , McLaughlin J A D , Nesbit M A , Moore C B T , Spence M S
Published: October 2022

Background

Ischaemia with normal coronary arteries (INOCA) may result in disabling symptoms and has an association with adverse long-term prognosis. The diagnosis of INOCA necessitates invasive coronary angiography to perform a physiological evaluation of microvascular function.

The conjunctiva has a readily assessable microvascular network in which physiological parameters can be evaluated. We compared conjunctival haemodynamics in patients with and without coronary microvascular disease (MVD) to assess if systemic microvascular dysfunction was present in this coronary artery disease sub-group.

Methods

In this study, we recruited patients undergoing invasive coronary angiography for the investigation of angina or angina equivalent symptoms. All patients had physiologically insignificant epicardial disease (FFR≥0.80) and underwent a physiological evaluation of coronary microvascular function. We compared a group with evidence of coronary MVD (IMR≥25 or CFR<2.0); to a group of controls without MVD (IMR<25 and CFR≥2.0).

The conjunctival microvasculature was imaged using a previously validated combination of a smartphone and slit-lamp biomicroscope. The conjunctival vasculature was assessed using a semi-automated process of vessel diameter measurement and erythrocyte tracking to obtain haemodynamic parameters of microvascular function.

Results

A total of 111 patients were included (43 MVD and 68 controls). There were no differences in baseline demographics, co-morbidities, epicardial coronary disease severity or regular pharmacological therapies between the groups. Mean coronary flow reserve (CFR) was lower and mean index of microcirculatory resistance (IMR) higher in the MVD cohort (CFR 2.5±1.3 vs 5.2±2.5, p<0.001 and IMR 28.4±11.8 vs 13.7±5.0, p<0.001).

A total of 2295 conjunctival vessels were analysed. The mean number of vessels per patient was 21.0±12.8 (3.2±3.5 arterioles and 14.8±10.8 venules). Significant reductions in axial/cross-sectional velocity, wall shear rate and wall shear stress were observed in the MVD cohort. Table 1 demonstrates a comparison of conjunctival physiological parameters between the groups.

The most marked differences were observed in conjunctival arterioles. Due to the heterogenous size distribution of microvessels, arterioles were categorised into 2 diameter sub-groups (10–25 μm and 25–40 μm) for analysis (Table 2).

Conclusion

The reductions in microvascular blood flow velocity and rate that form the basis for the diagnosis of coronary microvascular dysfunction can be observed non-invasively in the bulbar conjunctiva microcirculation. Conjunctival vascular imaging may have utility as a non-invasive imaging modality to both diagnose microvascular dysfunction and augment conventional cardiovascular risk stratification.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Belfast Trust Heart Trust Fund and Northern Ireland Chest Heart and Stroke
Prognostic value of stress cardiac magnetic resonance at 3 Tesla in patients with known or suspected coronary artery disease
Authors: Punawakul S , Vorasettakarnkit Y , Chattranukulchai P , Tumkosit M
Published: October 2022

Background

Adenosine stress cardiac magnetic resonance imaging (adenosine stress CMR) is increasingly playing a role in the non-invasive test for the diagnosis of coronary artery disease (CAD). But there are limited data on the prognostic value of predicting CAD-related death and major cardiac events (MACE) by adenosine stress CMR at 3 Tesla in Thailand.

Objectives

This study aimed to assess the prognostic value of adenosine stress CMR at 3 Tesla to predict CAD-related death, MACE, and all-cause mortality during two years in patients with known or suspected CAD.

Methods

This is a single-center retrospective cohort study in patients with suspected or known CAD who underwent adenosine stress CMR at 3 Tesla between 1 September 2017 to 31 August 2019 at our hospital. The data were collected from electronic medical record reviews. Only patients who completed two years of follow-up or had events were included in this study.

Results

A total of 633 patients were analyzed (age 66.21±12.60 years, 53.7% male, 31.9% known CAD), within two years of follow-up, we observed 15 deaths (2.4%) occurred with 5 CAD-related death (0.8%) and 10 non-fatal myocardial ischemia (non-fatal MI) (1.6%). The presence of ischemia in adenosine stress CMR at 3 Tesla is associated with CAD-related death, but the events rates of acute MI are about the same in both groups (1.4% vs. 1.7%).

Patients who underwent CAG after CMR were analyzed and categorized into normal coronary arteries, insignificant CAD, and significant CAD groups. Divided the positive adenosine stress CMR group to 6.8%, 7.7%, 85.5%, and the negative adenosine stress CMR group to 15.4%, 38.5%, 42.6%, respectively. So, the adenosine stress CMR at 3 Tesla has sensitivity at 94.34%, Specificity 29.17%, PPV 85.47%, and NPV 53.85%.

Conclusions

In this cohort study, patients with positive adenosine stress CMR were associated with an increased risk of CAD-related death. High-risk patients who received revascularization had a good prognosis as those with a negative adenosine stress perfusion CMR. Therefore, adenosine stress CMR at 3 Tesla is an effective tool with high sensitivity and positive predictive value for identifying high-risk patients for further treatment and procedures.

Funding Acknowledgement

Type of funding sources: None.
Development and validation of non-invasive endothelial shear stress (ESS) estimations of coronary artery haemodynamics using computational modelling
Authors: Chan J , Thum K Y , Comella A , Kalman E , Carberry J , Gregory S , Cameron J , Brown A
Published: October 2022

Background

Vascular remodelling is influenced by various biomechanical forces such as endothelial shear stress (ESS) and is associated with development and progression of coronary artery disease (CAD). ESS is the parallel frictional force exerted by blood flow on the endothelial luminal surface of the arterial wall. While ESS may not be the only cause of atherosclerosis, it is postulated that low ESS creates a pro-atherogenic environment and high ESS is athero-protective. Computational fluid dynamics (CFD) is an engineering method used to analyse fluid flow and has been increasingly applied to simulate ESS in cardiovascular research. However, current CFD-derived ESS estimates have never been validated and can display significant variability between research groups.

Purpose

This study aims to provide a comparative analysis of coronary flow using in-silico modelling of coronary flow and particle image velocimetry (PIV).

Methods

A proximal left anterior descending (pLAD) coronary phantom model was constructed from a patient who had received same day cardiac computed tomography angiography (CTCA) and invasive coronary haemodynamic (Combowire XT) assessment. Patient-specific coronary flow data was applied to CFD boundary conditions and a mock circulatory loop. CFD was validated using PIV under steady flow in a 4-times-scaled model. Same plane velocity field and flow patterns (at mid-luminal of pLAD) from both in-silico and in-vivo data were compared and analysed.

Results

Mean velocity contours and magnitude were analysed from CFD and PIV. Patient specific average peak velocity obtained from invasive assessment was 0.21m/s. Patient-specific velocity average from CFD was 0.22m/s. The approximated magnitude difference is 4.7%. Both same-axial average cross-sectional velocity estimated by CFD-pLAD and PIV-pLAD are 0.087m/s. Velocity contours and flow patterns simulated in the CFD were also comparable with the PIV results.

Conclusion

Simulation data from CFD correlate well with experimental PIV results. This early data allows for a non-invasive approach to determine patient-specific coronary haemodynamics (such as velocity profiling and ESS) and form the basis of personalising cardiovascular risk. Insights from this work may aid future development of a novel tool that incorporates CFD-derived ESS estimates with patient-specific risk factors to better predict rapid CAD progression.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Cardiac Society of Australia and New Zealand Monash Institute of Medical Engineering
Stent expansion evaluated by optical coherence tomography and subsequent outcomes
Authors: Lee B , Kim B G , Baraki T G , Kim J S , Lee Y J , Lee S J , Hong S J , Ahn C M , Shin D H , Kim B K , Ko Y G , Choi D H , Honh M K , Jang Y S
Published: October 2022

Background

Regarding stent expansion indexes, previous optical coherence tomography (OCT) studies have shown minimal stent area (MSA) to be most predictive of adverse events.

Purpose

We sought to evaluate the impact of various stent expansion indexes by post-stent OCT on long-term clinical outcomes, and hence to find OCT-defined optimal stent expansion criteria.

Methods

Of the patients registered in the Yonsei OCT registry, a total of 1071 patients with 1123 native coronary artery lesions treated with new-generation drug-eluting stents under the OCT guidance and analyzable final post-stent OCT were included. Stent expansion indexes and different suboptimal stent expansion criteria were evaluated for their association with device-oriented clinical endpoints (DoCE) including cardiac death, target vessel-related myocardial infarction (TVMI) or stent thrombosis, and target lesion revascularization. Major safety events (MSE) included cardiac death, TVMI or stent thrombosis.

Results

The median follow-up period was 40.6 (interquartile range 22.0–50.0) months. As a continuous variable, MSA, adaptive volumetric stent expansion (stent volume/adaptive reference lumen volume) and overall volumetric stent expansion (stent volume/post-stent lumen volume) were significantly predictive of DoCE. As a categorical criteria, MSA <5.0 mm2 (hazard ratio [HR] 3.80; 95% confidence interval [CI] 1.53–9.45), MSA/distal reference lumen area <90% (HR 2.13; 95% CI 1.10–4.14), and overall volumetric stent expansion ≥96.6% (HR 2.38; 95% CI 1.09–5.22) were independently associated with DoCE after adjusting for confounders, and a total malapposition volume ≥7.0 mm3 (HR 3.38; 95% CI 1.05–10.93) was linked to MSE.

Conclusions

This OCT study highlights that sufficient stent expansion to achieve adequate absolute MSA and relative MSA by distal reference lumen area and alleviate significant malapposition is important to improve clinical outcome, but overall stent overexpansion may have deleterious effect.

Funding Acknowledgement

Type of funding sources: None.
Long-term effects of phosphodiesterase-5 inhibitors on cardiovascular outcomes and death: a systematic review and meta-analysis of cohort studies
Authors: Soulaidopoulos S , Terentes-Printzios D , Ioakeimidis N , Aznaouridis K , Doundoulakis I , Tsioufis K , Vlachopoulos C
Published: October 2022

Background

Phosphodiesterase type 5 inhibitors (PDE-5i), which are widely used for the treatment of erectile dysfunction, have been found to exhibit systemic vascular benefits by improving endothelial function possibly lowering the risk for cardiovascular events and death.

Purpose

We sought to evaluate the effects of PDE5i on long-term cardiovascular outcomes and mortality.

Methods

A comprehensive search of electronic databases was conducted up to February 28, 2022. Cohort studies comparing PDE5i treatment at any dose with placebo or no treatment and a minimum follow-up duration of 6 months were considered eligible. The outcomes of interest were: (1) major adverse cardiovascular events (MACE) and (2) all-cause mortality. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated.

Results

Eight trials were included (1,152,106 subjects, 8.5% treated with PDE5i). All were males [median age 61.5 years (range 30–72.8)]. The median follow-up duration was 3.8 years (range 2.3–7.5) across the studies. PDE5i use was associated with significant reduction in the composite of MACE [RR 0.79, 95% confidence intervals (CI) 0.69–0.91] (Figure 1). In addition, the analysis of pooled data from 5 studies, after removal of a study with a relatively small sample size, demonstrated that the use of PDE5i was associated with a significantly lower risk of all-cause mortality (RR 0.70, 95% CI 0.53–0.91) (Figure 2). Focusing on patients with a history of coronary artery disease, PDE5i was also found to reduce the risk of all-cause mortality by 15% (RR 0.85, 95% CI 0.74–0.98).

Conclusion

The use of PDE5i in men with or without known coronary artery disease was associated with a lower risk of cardiovascular events and overall mortality. This information underlines that PDE5i could provide considerable clinical benefit beyond the treatment of ED and could instigate the conduction of further, large-scale randomized clinical trials.

Funding Acknowledgement

Type of funding sources: None.
Lipoprotein(a), cardiovascular events, and benefit of P2Y12 inhibition: insights from the PEGASUS-TIMI 54 trial
Authors: Patel S , Morrow D , Bonaca M , Palazzolo M , Jarolim P , Steg P G , Bhatt D , Storey R , Cohen M , Braunwald E , Sabatine M , O'Donoghue M
Published: October 2022

Background

Lp(a) plays a causal role in atherogenesis and may exert pro-thrombotic effects by inhibiting fibrinolysis owing to its structural homology with plasminogen. Patients with higher Lp(a) concentrations may derive greater benefit from anti-thrombotic therapy.

Purpose

We assessed whether patients with higher Lp(a) derive greater risk reduction from P2Y12 inhibition with ticagrelor vs. placebo on a background of aspirin therapy.

Methods

Lp(a) concentration was measured (Randox) in a prospective nested cohort of 8,967 pts enrolled in PEGASUS-TIMI 54, a randomized trial of ticagrelor vs. placebo in patients 1–3 years post MI (median follow-up: 2.7 y). Lp(a) was dichotomized at 200 nmol/L as an established threshold of risk. The prespecified MACE endpoint was CV death, MI or stroke, with KM rates reported at 3y. Cox proportional hazards were used to assess the relationship between Lp(a), MACE and treatment benefit. Models were adjusted for relevant baseline characteristics including apolipoprotein B.

Results

The median Lp(a) was 29 (25th-75th percentile: 12–137) nmol/L. A total of 1,053 pts (11.7%) had a high Lp(a) (≥200 nmol/L). In the pooled trial population, high Lp(a) concentration was associated with a 29% higher risk of MACE (9.1% vs 7.6%; adjusted hazard ratio [adj HR] 1.29, 95% confidence interval [CI] 1.02–1.62; p=0.03), including a 37% higher risk of MI (6.9% vs. 5.3%; adj HR 1.37, 95% CI 1.05–1.79; p=0.02). The hazard ratios for MACE with ticagrelor vs. placebo were 0.73 (95% CI 0.48–1.11) for patients with higher Lp(a) and 0.88 (95% CI 0.74–1.05) for patients with lower Lp(a) (p-interaction=0.41; Figure 1). The absolute risk reductions were 2.4% and 1.2%, respectively.

Conclusion

Lp(a) above 200 nmol/L identifies patients with prior MI at increased risk of MACE who may derive greater absolute risk reduction from treatment with ticagrelor. These exploratory observations provide insights for therapeutics that are evaluating the clinical benefit of Lp(a) reduction.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): The PEGASUS-TIMI 54 trial was funded by AstraZeneca