Coronary Angiography Research Articles

Percutaneous coronary intervention of in-stent restenosis: A three-arm analysis from SWEDEHEART

Abstract Background During the last decades, there have been substantial improvements in treatment techniques for percutaneous coronary intervention (PCI). Yet, in-stent restenosis (ISR) continues to pose significant challenges as they account for 10% of all PCI cases and are associated with worse outcome compared to de-novo lesions. When assessing ISR with PCI, balloon angioplasty with drug-coated balloons (DCB) is frequently used. Purpose Despite frequent use of DCB, there is a lack of long-term data ensuring the safety of DCB for ISR as no randomized trial has extended beyond a 3-year follow-up. We aimed to study the long-term outcome and conducted a nationwide three-arm investigation on the outcome of ISR, comparing DCB with drug-eluting stents (DES) or plain old balloon angioplasty (POBA) within a 5-year follow-up. Methods We conducted a nationwide analysis using the SWEDEHEART (Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry. The SWEDEHEART registry was used to include any ISR undergoing coronary angiography between June 11, 2013, and December 31, 2020. Target lesion revascularization (TLR) was the primary outcome. Secondary outcomes included all-cause mortality, myocardial infarction, and any PCI. The outcomes were analysed using a multivariable Cox regression model. Results A total of 9304 segments from 7987 patients were eligible. Compared to POBA, the use of DCB was associated with lower rates of TLR, hazard ratio (HR) 0.62 (95% confidence interval [CI]: 0.50-0.78), all-cause mortality, HR 0.60 (95% CI: 0.50-0.72), and any PCI, HR 0.78 (95% CI: 0.66-0.93). No difference was observed for myocardial infarction. Compared to DES, the use of DCB was associated with higher rates of TLR, HR 1.24 (95% CI: 1.08-1.42). No difference was observed for all-cause mortality, cardiovascular mortality, myocardial infarction, or any PCI. Conclusions In this nationwide analysis including any ISR undergoing PCI, the use of DCB showed superior outcomes compared to POBA within 5 years but higher rates of repeat revascularizations compared to DES. While DES demonstrated lower TLR rates than DCB, the lack of mortality differences indicates that DCB is a viable option, particularly for patients where DES might not be suitable, but that DES should be considered as the first line strategy.Table 1.5-year outcomeFigure 1.Kaplan-Meier curves

Elderly patients with decompensated heart failure: prospective analysis from the LECRA-HF registry

Abstract Background/Introduction Heart failure (HF) presents as a clinical syndrome associated with an adverse prognosis, increased mortality risk, and recurrent hospitalizations for HF (HHF). In Poland, there has been a persistent increase in the overall prevalence and hospitalizations of HF among patients. Each subsequent HHF is associated with progressively worsening prognosis. In Europe, HF is most prevalent in elderly individuals, rendering this patient group particularly susceptible to HF exacerbations. Purpose The aim of this study was to conduct a comprehensive analysis of the oldest patients (≥80 years) hospitalized due to HF decompensation, compared to the rest of the evaluated cohort, including overall mortality after median 46 months of observation. Methods The prospective registry of patients with HF decompensation (LECRA-HF) is an ongoing registry conducted at a tertiary cardiology center specializing in HF treatment. Patients enrolled in the registry (n=1394) were evaluated for the presence of cardiovascular risk factors, HF phenotype, laboratory, and echocardiographic findings, as well as overall mortality. Due to the frequent occurrence of HF in elderly patients, we arbitrarily chose to compare two cohorts of patients: those above (n=306) vs. below 80 years of age (n=1088). Results Median age of elderly patients was 84 [82-86] years, of which only 7.8% were >90 years of age. HFrEF was the most common HF phenotype, which, occurred less frequently in the elderly (54.4 vs 74.4%, P<0.001). In turn, HFpEF was more prevalent in elderly group (39.2 vs 17.7%, P<0.001). Elderly patients were more often female (45.1 vs 30.2%, P<0.001) and had more comorbidities: arterial hypertension (85.6 vs 78.6%, P=0.007), atrial fibrillation (61.1 vs 45.7%, P<0.001), renal failure (49.7 vs 28.5%, P<0.001) as well as peripheral arterial disease (17 vs 9.8%, P=0.005). Those patients had more frequently implanted cardiac pacemakers (28.6 vs 12.6%, P<0.001), but less often implantable cardioverter-defibrillators (7.9 vs 14.3%, P=0.003). During HHF they were less often qualified to elective coronary angiography (24.2 vs 31.5%, P=0.039). At discharge mineralocorticoid receptor antagonist were less often prescribed in that group (42.4 vs 50.3%, P=0.010). During long-term observation patients ≥80 years had a higher all-cause mortality (81 vs 67.4%, P<0.001, Panel A). Moreover, it was also higher elderly with NT-proBNP>4497 pg/mL (P<0.001) and LVEF<41% (P=0.014) (Panel B). Conclusion(s) Patients aged ≥80 years were characterized by a higher burden of comorbidities. They were more often qualified to cardiac pacemakers, but less often to implantable cardioverter-defibrillators and invasive coronary procedures. The most common HF phenotype was HFrEF, however with a significant increase in HFpEF. They exhibited significantly higher overall mortality compared to those <80 years old, which was associated with both LVEF and NT-proBNP levels.

Incidence and predictors of radial artery occlusion following transradial coronary procedures

Abstract Background Transradial access for percutaneous coronary procedures has grown in popularity because of its advantages over the femoral approach. However, the benefit is overshadowed by an increased rate of radial artery occlusion (RAO). We aim to assess incidence and predictors of RAO after transradial catheterization. The anatomic variations of the radial artery (RA) were also studied. Methods This prospective study enrolled 427 patients who underwent coronary angiography or angioplasty via transradial access. An ultrasound evaluation of forearm arteries was performed. In case of RAO, another ultrasound check-up was performed after 1 month and 3 months of the procedure. Results Our study population includes 288 patients (32.6% female). The mean age was 61.9 ± 11.1 years. RAO occured in 48 patients (11.24%), among whom spontaneous recanalization was observed within 3 months in 15 patients (32.6%). On multivariate analysis, a younger age (OR 0.642 [CI 95%: 0.480 – 0.858], P = 0.031), low periprocedural systolic blood pressure, (OR 0.598 [CI 95%: 0.415 – 0.862], P = 0.007), a small radial diameter (OR 0.371 [CI 95%: 0.323 – 0.618], P = 0.031), insufficient anticoagulation (OR 0.287 [CI 95%: 0.163 – 0.505], P < 0.001), occlusive hemostasis (OR 0.128 [CI 95%: 0.047 – 0.353], P < 0.001), and a long duration of hemostasis emerged as independent predictors of radial occlusion. The overall incidence of radial artery anatomic variations was 14,8% (n=63). Among these patients, 40 (63.5%) had a high radial origin, 18 (28.6%) had extreme radial artery tortuosity, and 5 (7.9%) had a full radioulnar loop. Conclusion The incidence and prevalence of radial artery occlusion is expected to increase. Insufficient heparinization and occlusive hemostasis are the main modifiable predictors. The preventive strategy should focus primarily on these 2 predictive factors.

ClinicAl verSus algorIthmic predictioN of Obstructive Coronary Artery Disease - the CASINO study

Abstract Background The estimation of pretest probability (PTP) is a key step when evaluating patients with suspected coronary artery disease (CAD). Current European guidelines recommend using an algorithm based on age, sex, and symptom typicality. However, many cardiologists do not regularly use this method, relying instead on overall clinical impression. The aim of this study was to compare clinical and algorithmic prediction of obstructive CAD in a set of symptomatic patients with suspected chronic coronary syndrome (CCS). Methods In this survey study, 10 cardiologists from were asked to estimate the probability of obstructive CAD (on a scale of 1-99% and without the aid of any score or algorithm) for 120 anonymized clinical vignettes of outpatients who underwent diagnostic workup for suspected CCS. The provided information included age, sex, symptom description, cardiovascular risk factors, and know comorbidities. Whenever non-invasive tests had been performed, physicians were also asked to estimate the probability of obstructive CAD after knowing that results. Obstructive CAD was defined as diameter stenosis ≥50% confirmed by invasive coronary angiography. Results Among the 120 included patients (62 women, mean age 61±10 years), symptoms consisted of chest pain in 104 and dyspnea in the remainder. The median PTP of obstructive CAD was 15% (IQR 10-25%) according to the ESC algorithm, and 30% (IQR 15-50%) according to cardiologists’ estimates (p<0.001). The observed prevalence of obstructive CAD was 20% (n=24), yielding suitable calibration for the ESC model (predicted vs. observed p=0.631), and significant overestimation for clinicians’ assessments (predicted vs. observed p=0.014) – Figure 1A. Despite using the same data, cardiologists’ PTP estimates varied widely within the same patients (mean inter-observer coefficient of variation 56%±22%). In a subset of 29 patients whose PTP was appraised twice by the same physicians, the mean absolute difference between assessments (intra-observer variability) was 22%±8%. The ESC algorithm showed fair discriminative power to identify patients with obstructive CAD (C-statistic 0.68, 95% CI 0.58-0.79, p=0.005), whereas the C-statistic for clinicians ranged from 0.53 to 0.72 (average 0.62±0.05, p values for comparisons 0.001-0.677) – Fig 1B. In the subset of 70 patients with prior non-invasive tests, clinicians significantly changed their predictions after knowing test results (mean absolute difference 22%±12%, p<0.001), improving their discriminative power significantly (mean change in C-statistic of 0.08±0.09, p=0.020). Conclusion Clinicians’ assessments of PTP in symptomatic patients display high inter- and intra-observer variability, and tend to overestimate the likelihood of obstructive CAD. Despite using more clinical data, cardiologists fail to outperform the ESC algorithm. The systematic use of this tool should be promoted in order to improve disease prediction and guide non-invasive testing.

Prevalence and prognostic relevance of non-obstructive coronary atherosclerosis in MINOCA: a meta-analysis of 35 studies

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) can result from a variety of pathological mechanisms, not always associated with atherosclerosis. It has been suggested to distinguish between patients without obstructive coronary artery disease (NObs-CAD, stenosis diameter 1-49%), and patients with smooth coronary arteries (NCA), but differences in terms of prognosis or therapeutic approaches have not been clearly elucidated. Objectives The aim of this study is to evaluate the prevalence and prognostic impact of NObs-CAD as assessed by invasive coronary angiography (ICA) in MINOCA. Methods A meta-analysis was performed including studies reporting the prevalence of NObs-CAD versus NCA in MINOCA patients. Data on prognosis stratified by the presence of NObs-CAD were collected. Random-effects models were used to estimate the prevalence of NObs-CAD. Pooled risk ratios (RR) with 95% confidence intervals (CI) for all-cause death, myocardial infarction (MI), and the composite of both outcomes of patients with NObs-CAD compared to NCA were calculated at short-term (<1 month), 1-year and long-term follow-up (more than 1 year). Results Thirty-five studies were analysed. The pooled prevalence of NObs-CAD estimated by ICA was 53% [95% CI 47-60%]. Heterogeneity was high (I2=98.0%), but none of the clinical and instrumental characteristics tested in meta-regression analyses had a significant impact on the I2, except for age (residual I2=97.2%, p=0.014) and geographical context. Specifically, studies conducted outside Europe reported a higher prevalence of NObs-CAD with lower I2 values. Thirteen studies provided prognostic data. The presence of NObs-CAD was associated with an increased risk of death or MI compared to NCA, as well as the risk of MI at 1-year follow-up (RR = 1.49 [95% CI 1.17-1.90] and RR = 1.80 [95% CI 1.26-2.59], respectively), whereas the risk of death was comparable. Similar results were observed at long-term, but not at short-term follow-up. Out of 13 studies, 4 provided information regarded the medications at discharge stratified by the presence or absence of NObs-CAD. NObs-CAD patients received more often aspirin (89% vs 69%; p<0.01), P2Y12-inhibitors (52% vs 29%; p<0.01), angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (53% vs 40%; p<0.01), beta-blockers (70% vs 57%; p<0.01), and statins (86% vs 60%; p<0.01) compared to NCA. Conclusions Stratification of patients according to the degree of coronary stenosis has prognostic implications in the setting of MINOCA, since NObs-CAD patients present a higher risk of reinfarction. Further dedicated trials are needed to clarify whether these patients may benefit from a tailored approach in terms of secondary prevention strategies.Central illustration

Coronary stent edge segments as determinant of clinical outcomes: An OCTOBER Trial Substudy

Abstract Background Small lumen dimensions and high plaque burden in stent edge segments are known risk factors for subsequent clinical events after percutaneous coronary intervention (PCI). The evidence using intravascular optical coherence tomography is scarce. Purpose This study aimed to characterize edge segments after PCI and the relation to clinical outcomes in the randomized OCTOBER trial on bifurcation PCI optimized using optical coherence tomography. Methods This is a predefined substudy of the OCTOBER Trial. Edge segments were analysed in detail for degree of stenosis and plaque composition using a dedicated software. Data was planned to be analysed using multi-level cox regression analysis, but descriptive statistics was applied due to very low event rates after OCT-guided PCI. Main endpoints were OCT-detected edge residual stenosis, lipid plaque, calcification, and dissections. Post PCI coronary angiography was analysed for diameter stenosis, edge segment length and minimal lumen diameter. Patients with cardiac events were diagnosed with angiography duringt the two-year follow-up period. Results A total of 597 patients were treated with OCT-guided PCI. Analysable final OCT scans with no additional treatment was available for 505 patients in the main vessel and for the side branch in 289 cases. At deadline for abstract submission 242 scans with 474 edges were analysed and included in preliminary results.Lesions with ≥30% diameter stenosis was found in 20% of proximal edges, 24% of distal edges and 37% of side branch (SB) edges. A plaque burdenOCT ≥180° was found in 74% of proximal edges, 48% of distal edges, and 52% of SB edges. A lipid plaque wafound in 35%, 11% and 14%, dissections in 15%, 6% and 12%, and ≥180° calcium was found in 7%, 4% and 4% of edges respectively. Six patients (1%) of the total OCT-guided population had an edge-related event during the median two-year follow-up. Only two of these 6 patients had post-procedural OCT-scans of the event-related edge, thus 4 of the cases were effectively angiographic guided. Conclusion Only a small fraction of edge segments in the OCTOBER Trial were left with residual edge disease exceeding protocol thresholds. This resulted in historically very low rate of edge related events. No evaluation of a stent edge by OCT in otherwise OCT guided patients appeared to be the main predictor of edge related events. Final results are presented at ESC 2024.

Prognostic impact of the extent of coronary artery disease in patients with acute transmural myocardial infarction undergoing complete percutaneous revascularization

Abstract Background The management of acute myocardial infarction has been revolutionised by the introduction of early coronary angiography and the reperfusion strategies. Recent studies support the standard of care of complete myocardial revascularization in all patients with ST-elevation myocardial infarction (STEMI) without assessing the prognostic role of the extent of coronary artery disease (CAD). Purpose To evaluate whether the extent of CAD in patients with STEMI has a prognostic impact independent of complete myocardial revascularization. Methods Observational cohort study of 365 patients with STEMI who underwent complete revascularization. For each patient the extent of CAD has been quantified using Gensini Score (GS), which takes into account both the severity and location of the lesions. The primary endpoint of the study was all-cause mortality, while cardiovascular mortality and a composite of major adverse cardiovascular events (MACE: cardiovascular mortality, recurrent acute myocardial infarction or myocardial revascularization and stroke) were defined as secondary endpoints. To assess the prognostic role of GS in predicting all-cause mortality, the area under the curve (AUC) was calculated. The best cut-off was determined as the one that maximized Youden's index (sensitivity + specificity - 1). Results Patients with a GS >80, indicating extensive coronary disease, had significantly higher rates of both cardiovascular [4 (16.7%) vs. 12 (3.5%); p = 0.002] and all-cause mortality [5 (20.8%) vs. 24 (7%); p = 0.016], than those with a GS ≤80. A GS >80 was demonstrated to be an independent predictor of all-cause mortality [hazard ratio = 5; 95% confidence interval: 1.5-16.8; p = 0.01] Conclusions The Gensini Score can identify high-risk patients with STEMI who may benefit from more intensive therapies to improve prognosis, although current guidelines do not specify treatment based on the extent of coronary disease.Long-term outcomes according to GSPrognostic value of GS

Haptoglobin polymorphism, vitamin E and mortality: the Ludwigshafen Risk and Cardiovascular Health Study

ObjectiveIn humans, haptoglobin (Hp) exists in two allelic forms, Hp1 and Hp2, that differ significantly in their ability to protect the organism from oxidative stress. It has been proposed that in patients with diabetes mellitus carriers of the Hp2-2 genotype may benefit from vitamin E supplementation. Aim of our study was to investigate if there is evidence regarding a potential interaction between the Hp polymorphism and vitamin E with regard to mortality in individuals at medium-to-high cardiovascular risk with and without diabetes mellitus.Research design and methodsData from 3176 participants of the Ludwigshafen Risk and Cardiovascular Health study, a monocentric hospital-based study of patients referred for coronary angiography, were analysed using Cox proportional hazard regression.ResultsParticipants with the Hp2-2 genotype demonstrated significantly lower Hp levels, while carriers of at least one Hp-2 allele displayed elevated levels of the inflammatory markers high-sensitive C reactive protein and serum amyloid A. No notable differences in comorbidities were observed among the various HP genotype groups. While the HP genotype showed no direct association with mortality, a borderline significant correlation between α-tocopherol plasma concentration and overall mortality was noted. An interaction between vitamin E status and the HP genotype regarding mortality risk was evident, particularly among patients with diabetes mellitus, with a p value of 0.021 for the interaction term. In restricted cubic splice analysis, patients with diabetes mellitus who are carriers of the Hp2-2 genotype seem to benefit from higher γ-tocopherol concentrations whereas for the other genotype groups there was a direct association with mortality risk.ConclusionParticularly in patients with diabetes mellitus we could show a significant interaction of γ-tocopherol plasma concentration and HP genotype. Carriers of the Hp2-2 genotype seemed to benefit from higher plasma concentrations of γ-tocopherol. Further research is warranted to elucidate the underlying mechanisms and potential therapeutic implications in cardiovascular disease management.

The utility of angiography-derived fractional flow reserve in predicting graft occlusions prior to bypass surgery

Abstract Background Occurrence of graft occlusion following coronary artery bypass graft (CABG) surgery has been linked to the presence of native coronary artery competitive flow (1). Despite its routine use in guiding revascularization, coronary angiography lacks sensitivity for assessing coronary stenosis significance. Data regarding the use of pressure-derived fractional flow reserve (FFR) to assess the hemodynamic significance of coronary stenoses prior to CABG are inconclusive (2) and the penetration of FFR in clinical routine is limited for various reasons (3). Different systems have been developed to predict FFR based on coronary angiographic images, eliminating pressure wires or hyperemic agents (4). Preliminary data demonstrated a high concordance between off-site angiography-derived FFR and pressure wire–based FFR (5-7). However, the use of this technique prior to CABG is not well studied. Purpose This study aims to correlate pre-CABG angiography-derived FFR with graft occlusion. Secondary endpoint is the correlation between the presence of at least one occluded bypass graft and overall mortality. Methods Retrospective study of patients undergoing CABG in whom a follow-up angiogram has been performed. Angiography-based FFR was calculated with a dedicated software (vFFR, CAAS 8.2 Workstation, Pie Medical Imaging), obtaining each major native coronary vessel before CABG. Post-CABG angiograms were conducted at least 6 weeks post-surgery to exclude graft-failures due to technical factors and thrombosis. Results From 2005 and 2014, 204 patients underwent pre-CABG angiography, with post-CABG angiograms at a median of 3.85 years [IQR 1.33-8.80] post-surgery. In total, 125 patients had to be excluded due to inadequate angiogram quality for vFFR assessment (outdated imaging system, improper vessel angles, vessel overlap, insufficient contrast). Consequently, 79 patients were suitable for pre-CABG vFFR analysis, including 132 grafted vessels (93 arterial and 39 saphenous grafts). The median patient age was 68 years [IQR 58-72] and mean time for clinical follow-up was 9.9±3.6 years. Vessels analyzed using vFFR were left anterior descending (LAD) (n=60, 45.5%), left circumflex (LCX) (n=39, 29.5%), ramus intermedius (RIM) (n=8, 6.1%) and right coronary artery (RCA) (n=25, 18.9%). Mean pre-CABG vFFR was 0.59±0.15. To predict graft occlusion, a vFFR cut-off value of 0.745 with an area under the curve (AUC) of 0.847 (95%CI 0.752–0.942) had a specificity of 0.722 and a sensitivity of 0.902 (Figure A). There was no difference in overall-mortality when comparing patients with at least one occluded bypass graft to those without (57.1% vs. 57.9%, p=0.949, Figure B). Conclusions vFFR can be used as a noninvasive tool to predict graft patency in patients undergoing CABG with acceptable sensitivity and specificity. Bypass graft occlusion did not correlate with overall-survival in this cohort.

Serum amyloid A-low-density-lipoprotein complex and cause-specific mortality in patients with suspected or known coronary artery disease: The ANOX Study

Abstract Background Serum amyloid A-low-density-lipoprotein (SAA-LDL) is a complex formed from the oxidative interaction between SAA and LDLs. A relatively small-scale study has shown that circulating SAA-LDL levels may serve as a prognostic marker in patients with stable coronary artery disease (CAD). However, the association between SAA-LDL and cause-specific mortality in patients with suspected or known CAD is unknown. Methods Serum SAA-LDL levels were measured in 2416 patients with suspected or known CAD undergoing elective coronary angiography. The outcomes were all-cause death, cardiovascular (CV) death, non-CV death, cancer death, and other non-CV death. Patients were followed up over a 3-year period. Results During the follow-up, 254 (10.5%) deaths occurred, including 88 (3.6%) CV deaths, 151 (6.3%) non-CV deaths, 66 (2.7%) cancer deaths, 85 (3.5%) other non-CV deaths, and 15 (0.6%) undetermined deaths. Stepwise regression analysis including baseline data on potential clinical confounders and established CV biomarkers (i.e., N-terminal pro-brain natriuretic peptide, high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein [hs-CRP]) revealed that the strongest independent determinant of SAA-LDL levels was hs-CRP (partial regression coefficient, 0.248; standard error, 0.010; p<0.001). After adjusting for potential clinical confounders and established CV biomarkers, the highest quartile of SAA-LDL levels (vs. the lowest quartile) was significantly associated with all-cause death (adjusted hazard ratio [aHR], 1.56; 95% confidence interval [CI], 1.05–2.34) and non-CV death (aHR, 1.76; 95% CI, 1.02–3.11), but not with CV death (aHR, 1.16; 95% CI, 0.62–2.20), cancer death (aHR, 1.68; 95% CI, 0.71–4.34), or other non-CV death (aHR, 1.65; 95% CI, 0.82–3.45) in the entire cohort. In patients with low hs-CRP levels (≤1.0 mg/L, n=1253), the highest quartile of SAA-LDL levels was significantly associated with all-cause death (aHR, 2.19; 95% CI, 1.11–4.57), non-CV death (aHR, 2.78; 95% CI, 1.05–8.79), and cancer death (aHR, 4.65; 95% CI, 1.12–31.9), but not with CV death (aHR, 1.22; 95% CI, 0.39–3.92) or other non-CV death (aHR, 1.68; 95% CI, 0.42–8.35). In contrast, the highest quartile of SAA-LDL levels was not significantly associated with all-cause death (aHR, 1.18; 95% CI, 0.72–1.96), CV death (aHR, 1.02; 95% CI, 0.45–2.31), non-CV death (aHR, 1.46; 95% CI, 0.75–2.91), cancer death (aHR, 1.35; 95% CI, 0.43–4.58), or other non-CV death (aHR, 1.38; 95% CI, 0.60–3.25) in patients with high hs-CRP levels (>1.0 mg/L, n=1163). Conclusions Elevated SAA-LDL levels were independently associated with all-cause and non-CV mortality, but unexpectedly not with CV mortality, in patients with suspected or known CAD. These associations were pronounced in patients with low hs-CRP levels (≤1.0 mg/L). The association between the SAA-LDL level and cancer mortality suggests its predictive utility in patients with low hs-CRP levels (≤1.0 mg/L).

Fractional flow reserve in saphenous vein grafts for the detection of myocardial ischemia determined by perfusion imaging

Abstract Background Fractional flow reserve (FFR) is recommended to guide revascularization of native coronary arteries. Revascularization decision-making for saphenous vein grafts (SVGs), however, is based on angiographic estimation of lesion severity, as studies exploring the value of FFR to detect perfusion imaging defined myocardial ischemia in SVGs are scarce. Purpose We aimed to define an optimal FFR threshold and compare its diagnostic performance with the traditional FFR cutoff and with percentage diameter stenosis (%DS) in patients evaluated for SVG disease using myocardial perfusion imaging (MPI) as the reference standard. Methods Symptomatic patients with prior coronary artery bypass grafting (CABG) who underwent single-photon emission computed tomography, positron emission tomography or stress perfusion cardiac magnetic resonance imaging, and had FFR measurements of one or more SVGs were included. Angiographic lesion severity of the SVG was measured using 2D quantitative invasive coronary angiography. We allocated and matched the myocardial territory subtended by the SVG to compare the values of FFR and %DS with ischemia determined by MPI. Results Included were 77 patients (mean age 72 ± 7 years; 86% male) with 91 SVGs. A total of 38 SVGs (42%) supplied an ischemic coronary territory. FFR and %DS correlated moderately (r= -0.51, P<0.001). The optimal cutoff value of FFR was ≤0.94, resulting in a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 63%, 75%, 65%, 74% and 70%, respectively (Figure 1). Corresponding values of FFR≤0.80 and DS%≥50 are shown in Figure 1 as well. Sensitivity, NPV and accuracy of FFR ≤0.94 outperformed that of FFR≤0.80, whereas specificity was lower. FFR≤0.94 outperformed %DS≥50 only in terms of sensitivity. Conclusions The optimal cutoff value of FFR for the detection of MPI-defined disease in SVGs is higher than the traditional FFR cutoff used to guide native coronary artery revascularization. Importantly, the increased sensitivity led to a higher diagnostic performance of the adjusted cutoff. However, the high prevalence of ischemia in post-CABG patients questions whether the optimal cutoff reflects ischemia caused by SVG obstruction.Diagnostic performance of FFR and %DS

Long-term clinical impact of routine follow-up coronary angiography of asymptomatic patients after complex percutaneous coronary intervention in the drug-eluting stent era

Abstract Background Drug-eluting stent (DES) implantation has become the standard for treating coronary artery disease (CAD). While routine follow-up coronary angiography (FUCAG) post-percutaneous coronary intervention (PCI) is not recommended in the 2nd generation DES era, its efficacy and necessity in complex PCI remains unclear. This study aims to investigate the utility of FUCAG after complex PCI. Methods From 2014 to 2020, a study was conducted on patients at our university medical center who underwent complex PCI. Out of a total of 4,098 individuals, after excluding 848 individuals with a follow-up period of less than 4 years and 288 individuals who experienced an event within a year, a total of 2,962 was enrolled. Follow-up coronary angiography (FUCAG) was defined as angiography performed between 6- and 18-months post-index PCI for lesion evaluation. To adjust for any differences in baseline characteristics between the groups, propensity score matching (PSM) was implemented. The primary outcome was defined as Major Adverse Cardiac Events (MACE), comprising all-cause death, myocardial infarction, and target-lesion revascularization. Results PSM was conducted to correct the difference in baseline characteristics between the two groups. In the Kaplan-Meier analysis, there was no difference between FUCAG and clinical follow-up for MACE (Log-rank: P=0.410). Cox proportional regression analysis revealed a hazard ratio (HR) of 0.55 with a 95% confidence interval (CI) of 0.64-1.27, indicating no statistically significant difference. Conclusions In our study, FUCAG did not demonstrate a clinical benefit in patients who underwent complex PCI compared to clinical follow-up. Therefore, clinical follow-up may be considered post-PCI surveillance after complex PCI.

False-positive cardiac troponin I values in healthy athletes post COVID-19 Infection: concerning insights from a prospective cohort study

Abstract Background Cardiac troponin I and T (cTnI, cTnT) are cardiac-specific biomarkers that detect and quantify cardiomyocyte injury. In patients with symptoms possibly indicating acute myocardial infarction (AMI), detection of elevated cTnT or cTnI concentrations usually mandates invasive coronary angiography. Accordingly, false-positive cTnT or cTnI concentrations could have detrimental consequences. Unfortunately, little is known about the prevalence and triggers of false-positive cTnI concentrations. Based on two index cases seen by one of us, we hypothesized that false-positive cTnI values may be common after COVID-19 infection and that macrotroponin, a complex formed between endogenous cTn autoantibodies and circulating cTn, may be the underlying cause. Purpose We aimed to test these hypotheses in a prospective cohort study. Methods We prospectively investigated professional athletes coming to the mandatory return to sports investigation at least 10 days after COVID-19 infection between 2022 and 2023 in an observational study. The presence of false-positive cTnI was centrally adjudicated in individuals that had elevated cTnI concentrations with one (or two) high-sensitivity cTnI assays, but normal high-sensitivity cardiac troponin T concentrations and normal electrocardiography (ECG), normal echocardiography, and normal cardiac magnetic resonance imaging (CMR). Divergences in hs-cTn concentrations were investigated using sex-specific upper limits of normal (ULN) of 4 different assays (hs-cTnI: Alinity/Abbott Diagnostic, hs-cTnI: Atellica/Siemens Healthineers, hs-cTnI: Access Beckman Coulter; hs-cTnT: Cobas/Roche Diagnostics). Athletes were instructed to cease training 48 hours before blood testing. Athletes with divergent hs-cTn assay results underwent further analysis for macrotroponin using sucrose gradient ultracentrifugation. Results Among 35 enrolled athletes (median age 24 years, 19 women and 16 men), 18 athletes had normal hs-cTn concentrations with all four hs-cTnT/I assays. In 17 athletes (48.6%), hs-cTn concentration was increased in at least one assay above the ULN, mostly one hs-cTnI method (hs-cTnI, Alinity) with normal concentrations of the other assays and normal cardiac imaging results. In contrast, two athletes had elevations in all hs-cTnI/T assays. Sucrose gradient ultracentrifugation provided evidence of macrotroponin in 15 of the 17 athletes (88%). Conclusions False-positive cTnI values are common after COVID-19 infection and should be considered in the differential diagnosis. Assay interference by macrotroponin seems to be the underlying mechanisms in most individuals. Documentation of normal hs-cTnT concentrations helps in the early detection of false-positive cTnI values.

Predictive value of plaque characteristics assessed by coronary computed tomography angiography and optical coherence tomography for identification of lesions causing ischemia

Abstract Background In patients with intermediate coronary stenosis, the functional assessment with fractional flow reserve (FFR) and the anatomical assessment with optical coherence tomography (OCT) have been widely used in clinical practice. Additionally, coronary computed tomography angiography (CTA) is commonly used non-invasive imaging technique for evaluating suspected coronary artery disease before being referred for angiography. Objectives This study sought to investigate the association between FFR and plaque characteristics assessed by coronary CTA and OCT in intermediate coronary stenosis. Methods Based on the prospective multicentre registry, a total of 159 patients including 339 coronary lesions with intermediate stenosis were included. All patients underwent coronary CTA before being referred for coronary angiography and both FFR measurement and OCT examination were performed during angiography. The stenotic lesion with FFR ≤0.80 was considered diagnostic of lesion causing ischemia. The predictive value of plaque characteristics assessed by coronary CTA and OCT for identifying lesions causing ischemia was analyzed. Results Stenosis severity and plaque characteristics on coronary CTA and OCT were different between the lesions causing ischemia versus not causing ischemia. On multivariate analysis, low attenuation plaque on coronary CTA (odds ratio [OR]= 2.78; P=0.038) and thrombus (OR=5.13; 0.042), plaque rupture (OR=3.25; P=0.017), and intimal vasculature on OCT (OR=2.57; P=0.012) were independent predictors for the lesions causing ischemia. Increasing number of these plaque characteristics offered incremental improvement in predicting the lesions causing ischemia. Conclusions Comprehensive anatomical evaluation of coronary stenosis may be able to provide additional supportive information for predicting the lesions causing ischemia.

The use of allopurinol in prophylaxis against contrast-induced nephropathy in patients undergoing percutaneous coronary intervention

Abstract Background Contrast-induced nephropathy (CIN) is a serious complication after percutaneous coronary intervention (PCI). Inflammation and development of reactive oxygen species are among the postulated mechanisms of CIN. Allopurinol with anti-inflammatory action could be a preventive method of CI-AKI. Aim of the work To determine the effect of adding allopurinol to hydration in the prevention of CIN in patients undergoing PCI, with or without hyperuricemia. Methods One hundred and seven patients with moderate to high Mehran score undergoing elective PCI were randomly allocated to the allopurinol (n=52) or the control group (n=55). Those in the allopurinol group (hyperuricemic n=25, and normouricemic n= 27) received allopurinol 300 mg one day and one hour before PCI beside intravenous hydration (1 ml/kg/hour) normal saline, a maximum of 100 ml/hour for 12 hours pre and post coronary angiography. Patients in the control group (hyperuricemic n=26 and normouricemic n=29), received the same intravenous hydration only. Serum creatinine and urea were measured before and 48 hours after the procedure while the uric acid level was measured before the procedure only. CIN was defined by a percentage increase in serum creatinine of ≥25% or absolute serum creatinine ≥0.5 mg/dl, 48 hours after PCI. Results The mean age of the studied patients was 59.6 ± 9.1 years old, 59% were male. No difference between both groups regarding baseline characteristics or medications. Average Mehran score was 9.0 ± 1.2. CIN was observed in 5 patients in the allopurinol group (9.6%) and 15 patients in the control group (27.3%) (P = 0.017). There was no significant difference between both groups regarding the contrast volume (179.8 ± 68.1 vs. 153.8 ± 57.9 ml, p: 0.052). Hyperuricemia had no significant effect on increasing the incidence of CI-AKI either in patients with or without CKD (p=0.964). Conclusion Allopurinol on the top of hydration was found to decrease the incidence of CIN following PCI in patients with moderate to high Mehran score for CIN. The anti-inflammatory action of allopurinol could be the mechanism of this favorable effect, as baseline uric acid didn't affect the results. Further multi-center study with a larger sample size is needed to offer more definite results.

Clinical value of single projection angiography-derived FFR in non-infarct related artery

Abstract Background Murray law-based quantitative flow ratio (μFR) is an emerging technique which requires only one projection of coronary angiography with similar accuracy with quantitative flow ratio (QFR). However, it has not been validated for evaluation of non-infarct related artery (non-IRA) in acute myocardial infarction (AMI) setting. Therefore, our study aimed to evaluate the diagnostic accuracy of μFR and the safety of deferring non-IRA lesion with μFR>0.80 in the setting of AMI. Methods μFR and QFR were analyzed for non-IRA lesions of AMI patients enrolled in the FRAME-AMI trial, consisting of fractional flow ratio (FFR)-guided PCI and angiography-guided PCI groups. Diagnostic accuracy of μFR was compared to QFR and FFR. Patients were classified by non-IRA μFR values 0.80 as a cutoff value. The primary outcome was vessel-oriented composite outcomes (VOCO), a composite of cardiac death, non-IRA-related MI, and non-IRA-related repeat revascularization. Results 443 patients (552 lesions) were eligible for μFR and QFR analysis. μFR showed acceptable correlation with FFR (R=0.777, P<0.001), comparable C-index with QFR to predict FFR≤0.80 (μFR vs. QFR: 0.926 vs. 0.961, P=0.070), and shorter total analysis time (mean 32.7sec vs. 186.9sec, P<0.001). Non-IRA with μFR>0.80 and deferred PCI had significantly lower risk of VOCO than non-IRA with performed PCI (3.4% vs. 10.5%; HR, 0.37; 95% CI, 0.14-0.99; P=0.048). Conclusion In multivessel AMI patients, μFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR≤0.80. Deferred non-IRA with μFR>0.80 showed lower risk of VOCO than revascularized non-IRA.

Impaired high-density lipoprotein-associated cholesterol efflux capacity predicts coronary rapid plaque progression

Abstract Background Rapid progression of coronary atherosclerotic plaques is recognized as a surrogate endpoint of cardiac ischemic events. Low high-density lipoprotein (HDL)-associated cholesterol efflux capacity (CEC) has been associated with atherosclerotic cardiovascular disease independent of HDL cholesterol (HDL-C) level. In this study, we aim to investigate the predictive role of CEC in rapid plaque progression (RPP). Methods We consecutively enrolled patients with stable angina from January 2017 to August 2019 in our hospital who underwent elective coronary angiography with at least one untreated coronary lesion. A follow-up angiography was performed at around 12 months. Afterwards, these patients were followed-up for every 3 months to June 2021. The primary endpoint was RPP during the 12-month angiography follow-up. The second endpoint was defined as a composite endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or unplanned coronary revascularization. Fluorescence-labeled cholesterol and J774 macrophages were used to measure CEC of ApoB-depleted serum samples. Results A total of 430 patients with 586 coronary lesions were included in the final analysis. During a mean follow-up of 12.7 ± 2.0 months, 120 lesions (20.5%) in 80 patients (18.6%) exhibited RPP. CEC, rather than HDL-C, was inversely associated with the extent of plaque progression (net luminal loss from the lowest to highest CEC quartile: 0.22±0.42 vs. 0.20±0.41 vs. 0.13±0.36 vs. 0.11±0.34 mm, P = 0.035). In multivariate analysis, baseline CEC was inversely associated with RPP independent of conventional risk and protective factors including HDL-C or apolipoprotein A-I. Subgroup analysis demonstrated that the association between CEC and RPP was more prominent in patients with high (≥4.02 mmol/L) than low (<4.02 mmol/L) total cholesterol. Finally, although patients with RPP had higher risk of the composite endpoint than those without RPP (P=0.012), no significant difference was observed between patients in different quartiles of CEC (P=0.720). Conclusions HDL-associated CEC is inversely associated with RPP in patients with coronary artery disease. HDL function assessment behaves as a better diagnostic biomarker than HDL-C for predicting RPP.

Diagnostic performance of coronary computed tomography angiography for coronary in-stent re-stenosis

Abstract Background Through the development of CT equipment and proper preparation before CT scanning, the accuracy of Coronary computed tomography angiography (CCTA) diagnosis of ischemic heart disease (IHD) is improving, and the role of CCTA in treatment decision is gradually expanding. The latest guidelines recommend CCTA as Class IIa to evaluate stent patency and native vessels in patients with chronic coronary disease. However, diagnostic performance of CCTA to evaluate stent patency in patients who underwent coronary stent was not clarified, respectively the role of CCTA in the evaluation of IHD in native coronary artery was established.. Purpose In the present study, we evaluate the agreement between CCTA and CAG in assessing stent patency in patients with de novo ischemic chest pain who underwent percutaneous coronary intervention (PCI) and evaluated which factors contribute to the differences. Methods From January 1, 2010 to December 31, 2020, we analyzed 845 patients who underwent new CCTA and CAG sequentially for the evaluation of chest pain previously underwent PCI. In CAG and CCTA, ISR is equally defined as a stenosis greater than 50% of the vessel diameter of within the stented segment or its edge (5-mm segments adjacent to the stent). The degree of In-stent restenosis was analyzed by an independently by quantitative coronary angiography (QCA). Results A total of 208 stents were analyzed, the pooled sensitivity and specificity for CCTA on the diagnosis of ISR were 0.78 (0.65-0.89) and 0.93 (0.88-0.96), respectively. LR+ and LR- were 11.19 (6.22-20.15) and 0.23 (0.14-0.39). As a result of analyzing the ISR diagnostic agreement of CCTA by dividing into ACS and CCD group, the agreement of CCTA for ISR diagnosis was relatively low in the ACS group (Sensitivity 0.69 (0.48-0.86) vs. 0.88 (0.69-0.97), specificity 0.92 (0.84-0.97) vs. 0.94 (0.86-0.98), LR+ 9 (4-20.24) vs. 13.9 (5.88-32.88), LR- 0.33 (0.19-0.6) vs. 0.13 (0.04-0.37)) (Table 1). As a result of analyzing related factors in cases of discrepancy in ISR diagnosis, the degree of stenosis in both ACS and CCD groups was mostly intermediate stenosis, which often required additional clinical evaluation (Figure 1). Conclusion When new ischemic chest pain occurred in a patient who previously underwent PCI, the diagnostic accuracy of ISR by CCTA differed depending on the patient’s IHD category. In the CCD group, the diagnostic usefulness of CCTA was comparable both native vessels and ISR, but not in the ACS group. As majority of ISR diagnostic discrepancies were in intermediate lesions, even in the ACS group, CCTA may be considered as a diagnostic tool.

A Genome-Wide Association Study (GWAS) of Takotsubo syndrome

Abstract Background Takotsubo syndrome (TS) is an acute cardiac condition of unknown etiology characterized by transient regional systolic dysfunction of the left and/or right ventricle. Several studies have suggested the importance of genetics; however, studies are limited and have presented conflicting results. Purpose To identify potential genetic risk variants associated with TS. Methods A case-control GWAS in three steps; I) A discovery study with Swedish takotsubo cases (n=260) and age- and sex-matched controls without heart disease from the UK Biobank (n=3034), II) A replication study of Swedish takotsubo cases (n=250) and sex- and age-matched Swedish controls without myocardial infarction from the Swedish coronary angiography and angioplasty register (n=229), III) A Meta-analysis of study I-II with extended controls from the UK-biobank (n=5161). Genotyping was performed using the Axiom® UK Biobank Genotyping Array including 820 000 single nucleotide polymorphisms (SNPs). After applying filters and QC control around 480 000 SNPs remained with a Bonferroni corrected p-value 1*10^-7, minor allele frequency (MAF 1.5-2%), Hardy-Weinberg (HWE) 10^-6. QC, filtering and analysis were performed in PLINK 1.9 and R v 4.0. Results In the discovery (I) 1490 SNP:s fulfilled a significance level of <10^-4, of which 36 SNP:s replicated (II) with a significance level of <10^-2, 11 reached a significance level of 10^-7 in the meta-analysis (III). One of the 36 SNP:s, rs1614887, replicated (II) with a significance level of 10^-3. This SNP is an intron variant in the butyrophilin subfamily 2 member A2 gene, a glycoprotein receptor involved in lipid, fatty-acid and sterol metabolism highly expressed in the heart. Of the 11 SNP:s with a significance level of 10^-7 in the meta-analysis (III) several risk variants were associated with psoriasis. Conclusions This is the largest GWAS of takotsubo syndrome performed so far, identifying one candidate gene and several potential risk variants. Further research of genetic risk variants in TS is warranted.

Type 2 diabetes rather than the presence of significant coronary stenoses is associated with quality of life in angiographied coronary patients

Abstract Chronic medical conditions such as type 2 diabetes (T2DM) or coronary artery disease (CAD) and their treatment have a crucial impact on patients’ daily life. The EQ-5D-5L questionnaire is a validated and widely used tool to measure the health-related quality of life (HRQL). We investigated and compared the HRQL in patients with or without T2DM and CAD. We included 481 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD in a tertiary care setting in Central Europe. Patients’ HRQL was measured using the EQ-5D-5L, comprising the EQ index calculated from the domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. A response rate of 88.1% was achieved. From our patients, 166 (34.5%) had T2DM according to ADA criteria, and 254 (52.8%) had significant CAD with stenoses ≥50% at angiography. Patients with T2DM showed significantly lower EQ index values than patients without T2DM (0.891 [IQR=0.783-0.970]) vs. 0.943, [IQR=0.861-1.0], p=0.002)). Regarding the different dimensions of the questionnaire, patients with T2DM reported to have significantly more problems with anxiety and depression (p=0.002) and mobility (p<0.001) than non-diabetic patients. EQ index values in contrast did not differ significantly between patients with vs. those without significant CAD. Accordingly, in analysis of covariance T2DM (F=7.38, p=0.007) but not significant CAD (F=1.74, p=0.183) predicted EQ index values after adjustment for age, sex and body-mass-index. We conclude that T2DM rather than the presence of significant CAD is associated with quality of life in angiographied coronary patients.