Ischemia-Guided Coronary Revascularization Following Lower-Extremity Revascularization Improves 5-Year Survival of Patients With Chronic Limb-Threatening Ischemia.

PURPOSE: To determine whether diagnosis of asymptomatic (silent) coronary ischemia using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) together with targeted coronary revascularization of ischemia-producing coronary lesions following lower-extremity revascularization can reduce adverse cardiac events and improve long-term survival of patients with chronic limb-threatening ischemia (CLTI). MATERIALS AND METHODS: Prospective cohort study of CLTI patients with no cardiac history or symptoms undergoing elective lower-extremity revascularization. Patients with pre-operative coronary computed tomography angiography (CTA) and FFRCT evaluation with selective post-operative coronary revascularization (FFRCT group) were compared with patients with standard pre-operative evaluation and no post-operative coronary revascularization (control group). Lesion-specific coronary ischemia was defined as FFRCT≤0.80 distal to a coronary stenosis with FFRCT≤0.75 indicating severe ischemia. Endpoints included all-cause death, cardiac death, myocardial infarction (MI) and major adverse cardiovascular (CV) events (MACE=CV death, MI, stroke, or unplanned coronary revascularization) during 5 year follow-up. RESULTS: In the FFRCT group (n=111), FFRCT analysis revealed asymptomatic (silent) coronary ischemia (FFRCT≤0.80) in 69% of patients, with severe ischemia (FFRCT≤0.75) in 58%, left main ischemia in 8%, and multivessel ischemia in 40% of patients. The status of coronary ischemia in the control group (n=120) was unknown. Following lower-extremity revascularization, 42% of patients in FFRCT had elective coronary revascularization with no elective revascularization in controls. Both groups received guideline-directed medical therapy. During 5 year follow-up, compared with control, the FFRCT group had fewer all-cause deaths (24% vs 47%, hazard ratio [HR]=0.43 [95% confidence interval [CI]=0.27-0.69], p<0.001), fewer cardiac deaths (5% vs 26%, HR=0.18 [95% CI=0.07-0.45], p<0.001), fewer MIs (7% vs 28%, HR=0.21 [95% CI=0.10-0.47], p<0.001), and fewer MACE events (14% vs 39%, HR=0.28 [95% CI=0.15-0.51], p<0.001). CONCLUSIONS: Ischemia-guided coronary revascularization of CLTI patients with asymptomatic (silent) coronary ischemia following lower-extremity revascularization resulted in more than 2-fold reduction in all-cause death, cardiac death, MI, and MACE with improved 5 year survival compared with patients with standard cardiac evaluation and care (76% vs 53%, p<0.001). CLINICAL IMPACT: Silent coronary ischemia in patients with chronic limb-threatening ischemia (CLTI) is common even in the absence of cardiac history or symptoms. FFRCT is a convenient tool to diagnose silent coronary ischemia perioperatively. Our data suggest that post-surgery elective FFRCT-guided coronary revascularization reduces adverse cardiac events and improves long-term survival in this very-high risk patient group. Randomized study is warranted to finally test this concept.

Diagnosis and treatment of ischemia-producing coronary stenoses improves 5-year survival of patients undergoing major vascular surgery.

OBJECTIVE: Patients undergoing vascular surgery procedures have poor long-term survival due to coexisting coronary artery disease (CAD), which is often asymptomatic, undiagnosed, and undertreated. We sought to determine whether preoperative diagnosis of asymptomatic (silent) coronary ischemia using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) together with postoperative ischemia-targeted coronary revascularization can reduce adverse cardiac events and improve long-term survival following major vascular surgery METHODS: In this observational cohort study of 522 patients with no known CAD undergoing elective carotid, peripheral, or aneurysm surgery we compared two groups of patients. Group I included 288 patients enrolled in a prospective Institutional Review Board-approved study of preoperative coronary CT angiography (CTA) and FFRCT testing to detect silent coronary ischemia with selective postoperative coronary revascularization in addition to best medical therapy (BMT) (FFRCT guided), and Group II included 234 matched controls with standard preoperative cardiac evaluation and postoperative BMT alone with no elective coronary revascularization (Usual Care). In the FFRCT group, lesion-specific coronary ischemia was defined as FFRCT ≤0.80 distal to a coronary stenosis, with severe ischemia defined as FFRCT ≤0.75. Results were available for patient management decisions. Endpoints included all-cause death, cardiovascular death, myocardial infarction (MI), and major adverse cardiovascular events (MACE [death, MI, or stroke]) during 5-year follow-up. RESULTS: The two groups were similar in age, gender, and comorbidities. In FFRCT, 65% of patients had asymptomatic lesion-specific coronary ischemia, with severe ischemia in 52%, multivessel ischemia in 36% and left main ischemia in 8%. The status of coronary ischemia was unknown in Usual Care. Vascular surgery was performed as planned in both cohorts with no difference in 30-day mortality. In FFRCT, elective ischemia-targeted coronary revascularization was performed in 103 patients 1 to 3 months following surgery. Usual Care had no elective postoperative coronary revascularizations. At 5 years, compared with Usual Care, FFRCT guided had fewer all-cause deaths (16% vs 36%; hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22-0.60; P < .001), fewer cardiovascular deaths (4% vs 21%; HR, 0.11; 95% CI, 0.04-0.33; P < .001), fewer MIs (4% vs 24%; HR, 0.13; 95% CI, 0.05-0.33; P < .001), and fewer MACE (20% vs 47%; HR, 0.36; 95% CI, 0.23-0.56; P < .001). Five-year survival was 84% in FFRCT compared with 64% in Usual Care (P < .001). CONCLUSIONS: Diagnosis of silent coronary ischemia with ischemia-targeted coronary revascularization in addition to BMT following major vascular surgery was associated with fewer adverse cardiovascular events and improved 5-year survival compared with patients treated with BMT alone as per current guidelines.

Long-term prognostic implications of CT angiography-derived fractional flow reserve: Results from the DISCOVER-FLOW study.

BACKGROUND & OBJECTIVES: The long-term prognostic implications of CT angiography-derived fractional flow reserve (FFRCT) remains unclear. We aimed to explore the long-term outcomes of FFRCT in the first-in-human study of it. MATERIALS & METHODS: A total of 156 vessels from 102 patients with stable coronary artery disease, who underwent coronary CT angiography (CCTA) and invasive FFR measurement, were followed. The primary endpoint was target vessel failure (TVF), including cardiovascular death, target vessel myocardial infarction, and target vessel revascularization. Outcome analysis with FFRCT was performed on a per-vessel basis using a marginal Cox proportional hazard model. RESULTS: During median 9.9 years of follow-up, TVF occurred in 20 (12.8%) vessels. FFRCT â€‹≤0.80 discriminated TVF (hazard ratio [HR] 2.61, 95% confidence interval [CI] 1.06, 6.45). Among 94 vessels with deferral of percutaneous coronary intervention (PCI), TVF risk was inversely correlated with FFRCT â€‹(HR 0.62 per 0.1 increase, 95% CI 0.44, 0.86), with the cumulative incidence of TVF being 2.6%, 15.2%, and 28.6% for vessels with FFRCT â€‹>0.90, 0.81-0.90, and ≤0.80, respectively (p-for-trend 0.005). Predictive value for clinical outcomes of FFRCT was similar to that of invasive FFR (c-index 0.79 vs 0.71, P â€‹= â€‹0.28). The estimated TVF risk was higher in the deferral of PCI group than the PCI group for vessels with FFRCT ≤0.81. CONCLUSION: FFRCT showed improved long-term risk stratification and displayed a risk continuum similar to invasive FFR. CLINICAL TRIAL REGISTRATION: NCT01189331.

Association between carotid and coronary atherosclerotic plaque morphology: a virtual histology intravascular ultrasound study.

Background and Aim: Atherosclerosis is considered to be a systemic disease; however, evidence exists on the heterogeneous nature of atherosclerotic disease. To date, continuous research seeks to determine the morphological differences between carotid and coronary artery disease. This study aimed to evaluate the relationship of morphological characteristics assessed by virtual histology intravascular ultrasound (VH-IVUS) between carotid and coronary plaque composition among patients with and without a history of cerebrovascular events. Methods: This study was a single-center prospective study (n = 100; age 69.6 ± 8.4). All patients were scheduled for carotid or coronary artery stenting and underwent VH-IVUS examination of the carotid and coronary arteries before intervention. Results: There was a modest, but statistically significant correlation between the carotid and coronary necrotic core ([NC] r = 0.46, P < 0.01), fibrofatty ([FF] r = 0.38, P < 0.01), dense calcium (r = 0.56, P < 0.01), and fibrous (r = 0.42, P < 0.01) plaque composition. The high amount of NC was detected in both arteries of the carotid artery stenting (CAS) group with higher proportion in the coronary artery (20.2% ± 9.4 % vs. 22.7% ± 6.8%, P = 0.02). More fibrolipid content was observed in carotid plaque compared to coronary (19.6% ± 9.9% vs. 12.2% ± 8.1%, P < 0.01). Patients with a history of cerebrovascular events had a numerically greater proportion of necrotic tissue in the carotid artery compared to asymptomatic and symptomatic CAS group patients (23.5% ± 10.7% vs. 18.9% ± 8.2% and 18.7% ± 9.5%, P = 0.11). Conclusion: The percentage of all analyzed plaque components was moderately correlated between coronary and carotid artery plaques. Nevertheless, the proportion of NC plaque tissue was greater in the coronary arteries, while the carotid arteries showed more %FF atherosclerotic lesions. CAS group patients with a history of cerebrovascular events had a tendency of greater proportion of necrotic tissue in analyzed carotid plaques compared to others in the CAS group. Relevance for Patients: In this study, we found that patients with a history of cerebrovascular event had a tendency of increased NC content in culprit lesion of carotid artery. Complementary use of non-invasive and invasive imaging modalities allows to detect high-risk atherosclerotic plaques and adjust treatment strategy.

Long-term prognostic implications of hemodynamic and plaque assessment using coronary CT angiography.

BACKGROUND AND AIMS: Hemodynamic and plaque characteristics can be analyzed using coronary CT angiography (CTA). We aimed to explore long-term prognostic implications of hemodynamic and plaque characteristics using coronary CT angiography (CTA). METHODS: Invasive fractional flow reserve (FFR) and CTA-derived FFR (FFRCT) were undertaken for 136 lesions in 78 vessels and followed-up to 10 years until December 2020. FFRCT, wall shear stress (WSS), change in FFRCT across the lesion (ΔFFRCT), total plaque volume (TPV), percent atheroma volume (PAV), and low-attenuation plaque volume (LAPV) for target lesions [L] and vessels [V] were obtained by independent core laboratories. Their collective influence was evaluated for the clinical endpoints of target vessel failure (TVF) and target lesion failure (TLF). RESULTS: During a median follow-up of 10.1 years, PAV[V] (per 10% increase, HR 2.32 [95% CI 1.11-4.86], p = 0.025), and FFRCT[V] (per 0.1 increase, HR 0.56 [95% CI 0.37-0.84], p = 0.006) were independent predictors of TVF for the per-vessel analysis, and WSS[L] (per 100 dyne/cm2 increase, HR 1.43 [1.09-1.88], p = 0.010), LAPV[L] (per 10 mm3 increase, HR 3.81 [1.16-12.5], p = 0.028), and ΔFFRCT[L] (per 0.1 increase, HR 1.39 [1.02-1.90], p = 0.040) were independent predictors of TLF for the per-lesion analysis after adjustment for clinical and lesion characteristics. The addition of both plaque and hemodynamic predictors improved the predictability for 10-year TVF and TLF of clinical and lesion characteristics (all p < 0.05). CONCLUSIONS: Vessel- and lesion-level hemodynamic characteristics, and vessel-level plaque quantity, and lesion-level plaque compositional characteristics assessed by CTA offer independent and additive long-term prognostic value.

Four-Year Outcomes of Left Main Percutaneous Coronary Intervention with a Bioresorbable Scaffold in the Circumflex Ostium.

Objectives: The study aimed to investigate the long-term outcomes of a double stent scaffold strategy in patients with left main (LM) bifurcation lesions involving the ostium of the left circumflex artery (LCX), utilizing a drug-eluting stent (DES) in the LM extending into the left anterior descending artery (LAD) and a bioresorbable vascular scaffold (BVS) in the LCX ostium. Background: The high occurrence of in-stent restenosis of the LCX ostium is the major limitation of percutaneous coronary intervention (PCI) for LM lesions with a two-stent strategy. Methods: This was a single-center, prospective, single-arm study of 46 consecutively enrolled patients with a stable coronary artery disease and significant unprotected LM distal bifurcation disease. Patients underwent imaging-guided PCI using DES in the LM-LAD and BVS in the LCX using a T-stent or mini-crush technique. The primary outcome at four years was the composite of death, myocardial infarction, stroke, and target lesion revascularization (TLR). Results: At four years, the primary outcome was identified in 9 patients (19.6%). All events were TLRs except one myocardial infarction due to BVS thrombosis. Seven of the eight TLRs were a result of side branch BVS restenosis. Univariate predictors of the 4-year outcome were higher LDL cholesterol and BVS size ≤2.5 mm. On multivariate analysis, LCX lesion preparation with a cutting balloon and post-procedure use of intravascular ultrasound for optimization were found to be independent protective factors of MACE. Conclusions: In selected patients with LM distal bifurcation disease, an imaging-guided double stent scaffold strategy with DES in the LM and BVS in the LCX ostium was technically successful in all patients and was reasonably safe and effective for four years.

Coronary revascularization of patients with silent coronary ischemia may reduce the risk of myocardial infarction and cardiovascular death after carotid endarterectomy.

BACKGROUND: Major adverse cardiac events (MACEs) are the primary cause of death after carotid endarterectomy (CEA). We sought to determine whether selective coronary revascularization of CEA patients with asymptomatic coronary ischemia can reduce the risk of MACEs, myocardial infarction (MI), and cardiac death after endarterectomy compared with CEA patients receiving standard cardiac evaluation and care. METHODS: Two groups of patients with no cardiac history or symptoms undergoing elective CEA were compared. Group I: patients enrolled in a prospective study of noninvasive preoperative cardiac evaluation using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) to detect asymptomatic (silent) coronary ischemia with selective postoperative coronary revascularization. Group II: matched Control patients with standard preoperative cardiac evaluation and no postoperative coronary revascularization. Lesion-specific coronary ischemia in group I was defined as FFRCT ≤ 0.80 distal to coronary stenosis with severe ischemia defined as FFRCT ≤ 0.75. End points included MACEs, cardiac death, MI, cardiovascular (CV) death, stroke, and all-cause death through 3-year follow-up. RESULTS: Group I (n = 100) and group II (n = 100) patients were similar in age (68 vs 67 years), gender (65% vs 62% male), comorbidities, and indications for CEA (53% vs 48% symptomatic carotid stenosis). In group I, FFRCT analysis revealed lesion-specific coronary ischemia in 57% of patients, severe coronary ischemia in 44%, left main ischemia in 7%, and multivessel ischemia in 28%. The status of coronary ischemia in group II was unknown. CEA was performed without complications in both groups, and all patients received optimal postoperative medical therapy. In group I, elective coronary revascularization was performed in 33 patients (27 percutaneous coronary intervention; 6 coronary artery bypass grafting) 1 to 3 months after CEA. Group II patients had no elective coronary revascularization. During 3-year follow-up, compared with group II, group I patients had fewer MACEs (4% vs 17%, hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63], P = .004), fewer cardiac deaths (2% vs 9%, HR: 0.20 [95% CI: 0.04-0.95], P = .030), fewer MIs (3% vs 17%, HR: 0.16 [95% CI: 0.05-0.54], P = .001), and fewer CV deaths (2% vs 12%, HR: 0.16 [95% CI: 0.004-0.07], P = .009). There were no significant differences in the rates of stroke or all-cause death. CONCLUSIONS: Preoperative diagnosis of silent coronary ischemia with selective coronary revascularization after CEA may reduce the risk of MACEs, cardiac death, MI, and CV death during 3-year follow-up compared with CEA patients receiving standard cardiac evaluation and care.

Comparative Analysis of the Most Important Cardiovascular Risk Factors Based on Cross-Sectional Studies in the Population of Latvia.

Background and Objectives: The aim of the study was to analyze the prevalence of cardiovascular risk factors (RFs) in Latvia from the population-based cross-sectional study performed in 2019−2020 and to compare the results with a similar study done in 2009−2010. Materials and Methods: The target sample of 6000 individuals representing a cross-section of Latvia's inhabitants (aged 25−74) was formed using stratified two-stage cluster sampling. The survey had two components: (1) an interview using a pre-specified questionnaire and (2) physical examination (height, weight, arterial pressure) and collection of venous blood samples to measure levels of fasting glucose (Glu), total cholesterol (TC), high and low-density lipoprotein cholesterol (HDL-C/LDL-C), and triglycerides (Tg). In total, 4070 individuals were interviewed (32% non-response), from which 2218 (55%) individuals underwent physical examination and collection of blood samples. Results: The most frequently observed RFs were high LDL-C (62.0%), smoking (45.3%), and arterial hypertension (36.8%), while the prevalence of self-reported high cholesterol and hypertension was 19.3 and 18.6%, respectively. A decrease in the prevalence of hypertension, high LDL-C, and Glu was noted. Smoking decreased in younger men. The mean number of five most important cardiovascular RFs was 2.0 (95% confidence interval (CI) 2.0, 2.1); 2.3 (95% CI 2.2, 2.4) for men and 1.8 (95% CI 1.7, 19) for women. The average number of RFs has decreased by 0.3 in 10 years, t(5883) = −7.2, p < 0.001. Conclusions: Although the prevalence of cardiovascular RFs remains noteworthy, an improvement in the risk profile of the Latvian population has been observed over the past decade. The study shows subjective self-underestimation of cardiovascular risk.

What Is Hidden Behind Yellow Pixels: from Pathology to Intravascular Imaging of Atherosclerotic Plaque.

PURPOSE OF REVIEW: Intravascular imaging systems can identify lipid-rich and vulnerable plaques and help in treatment guidance. The comparability of different intracoronary imaging methods remains unclear. In this paper, we review atherosclerotic plaque pathology, plaque-stabilising effects of different lipid-lowering therapies and usage of intravascular imaging modalities. We present the results of our study in which we evaluated the correlation of the intravascular ultrasound iMAP system (iMAP-IVUS) and near-infrared spectroscopy (NIRS) in the diagnosis of vulnerable coronary plaques. RECENT FINDINGS: Lipids have an essential contribution to plaque evolution and vulnerability. Increase in plaque vulnerability alone even without increase in plaque burden defines progression of atherosclerosis. Lipidic tissue has a significant diagnostic value in patient risk stratification and can serve as a treatment target. Different vulnerable plaque parameters can be visualised with iMAP-IVUS and NIRS. Intravascular imaging systems can differ with regard to their sensitivity, specificity and limitations. Lipid-lowering therapy is crucial in plaque stabilisation.

Plasma circulating microRNAs in patients with stable coronary artery disease - Impact of different cardiovascular risk profiles and glomerular filtration rates.

BACKGROUND AND AIM: Plasma circulating microRNA (miRNA)-126, -145, and -155 are associated with vascular remodeling, atherosclerotic lesion formation, and plaque vulnerability. In this study, we evaluated the levels of plasma circulating miRNAs in patients with stable coronary artery disease (CAD), different cardiovascular risk profiles, and different glomerular filtration rates (GFR). METHODS AND RESULTS: Forty patients with stable CAD admitted for elective percutaneous coronary intervention (PCI) were enrolled in a prospective study. Before PCI, fasting blood samples were obtained to evaluate clinical parameters and miRNA-126 and miRNA-155 expression. The GFR was calculated by the MDRD and CKD-EPI formulas, and the severity of CAD was calculated according to the SYNTAX score. All these parameters were correlated with miRNAs. The association between miRNA levels and clinical characteristics was evaluated. The expression of miRNA-126 positively correlated with a higher SYNTAX score (r = 0.337; p=0.034); however, no significant correlations between miR-126, GFR, and clinical characteristics were observed. Higher plasma levels of miRNA-155 correlated with increased levels of triglycerides (r = 0.317; P = 0.049), C-peptide (r = 0.452; P = 0.011), and the HOMA index (r = 0.447; P = 0.012) and a higher body mass index (BMI) (r = 0.385; P = 0.015). GFR and miRNA-155 (MDRD - Rho=0.353; P = 0.027. CKD-EPI - Rho=0.357; P = 0.026) were found to have a moderate correlation, although miRNA-155 had no correlation with the SYNTAX score. CONCLUSION: Plasma circulating miRNA-126 levels were increased in patients with severe atherosclerosis as determined by the SYNTAX score. Elevated miRNA-155 expression was observed in patients with Stage 1 GFR but was lower in patients with Stages 2 and 3 GFR. Plasma circulating miRNA-155 had positive correlations with higher levels of BMI, HOMA index, C-peptide, and triglycerides. RELEVANCE FOR PATIENTS: Although further investigations are needed to confirm the role of miRNA-155 and miRNA-126, they may serve as potential biomarkers detecting severity of CAD, lowering of kidney function and metabolic syndrome.

Diagnosis of silent coronary ischemia with selective coronary revascularization might improve 2-year survival of patients with critical limb-threatening ischemia.

BACKGROUND: Patients with critical limb-threatening ischemia (CLTI) have had poor long-term survival after lower extremity revascularization owing to coexistent coronary artery disease. A new cardiac diagnostic test, coronary computed tomography-derived fractional flow reserve (FFRCT), can identify patients with ischemia-producing coronary stenosis who might benefit from coronary revascularization. We sought to determine whether the diagnosis of silent coronary ischemia before limb salvage surgery with selective postoperative coronary revascularization can reduce the incidence of adverse cardiac events and improve the survival of patients with CLTI compared with standard care. METHODS: Patients with CLTI and no cardiac history or symptoms who had undergone preoperative testing to detect silent coronary ischemia with selective postoperative coronary revascularization (group I) were compared with patients with standard preoperative cardiac clearance and no elective postoperative coronary revascularization (group II). Both groups received guideline-directed medical care. Lesion-specific coronary ischemia in group I was defined as FFRCT of ≤0.80 distal to a stenosis, with severe ischemia defined as FFRCT of ≤0.75. The endpoints included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), major adverse CV events (i.MACE; CV death, MI, unplanned coronary revascularization, stroke) through 2 years of follow-up. RESULTS: Groups I (n = 111) and II (n = 120) were similar in age (66 ± 9 vs 66 ± 7 years), gender (78% vs 83% men), comorbidities, and surgery performed. In group I, unsuspected, silent coronary ischemia was found in 71 of 103 patients (69%), with severe ischemia in 58% and left main coronary ischemia in 8%. Elective postoperative coronary revascularization was performed in 47 of 71 patients with silent ischemia (66%). In group II, the status of silent coronary ischemia was unknown. The median follow-up was >2 years for both groups. The 2-year outcomes for groups I and II were as follows: all-cause death, 8.1% and 20.0% (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.18-0.84; P = .016); CV death, 4.5% and 13.3% (HR, 0.32; 95% CI, 0.11-0.88; P = .028); MI, 6.3% and 17.5% (HR, 0.33; 95% CI, 0.14-0.79; P = .012); and major adverse CV events, 10.8% and 23.3% (HR, 0.44; 95% CI, 0.22-0.88; P = .021), respectively. CONCLUSIONS: The preoperative evaluation of patients with CLTI and no known coronary artery disease using coronary FFRCT revealed silent coronary ischemia in two of every three patients. Selective coronary revascularization of patients with silent coronary ischemia after recovery from limb salvage surgery resulted in fewer CV deaths and MIs and improved 2-year survival compared with patients with CLTI who had received standard cardiac evaluation and care. Prospective controlled studies are required to further define the role of FFRCT in the evaluation and treatment of patients with CLTI.

Diagnosis and management of silent coronary ischemia in patients undergoing carotid endarterectomy.

BACKGROUND: Coronary artery disease is the primary cause of death in patients with carotid artery disease and silent ischemia is a marker for adverse coronary events. A new noninvasive cardiac diagnostic test, coronary computed tomography-derived fractional flow reserve (FFRCT) can reliably identify ischemia-producing coronary stenosis in patients with coronary artery disease and help to select patients for coronary revascularization. The purpose of this study is to determine the prevalence of silent coronary ischemia in patients undergoing carotid endarterectomy (CEA) and to evaluate the usefulness of FFRCT in selecting patients for coronary revascularization to decrease cardiac events and improve survival. METHODS: Patients with no cardiac history or symptoms admitted for elective CEA were enrolled in a prospective, open-label, institutional review board-approved study and underwent preoperative coronary computed tomography angiography (CTA) and FFRCT with results available to physicians for patient management. Lesion-specific coronary ischemia was defined as FFRCT of 0.80 or less distal to a focal coronary stenosis with an FFRCT of 0.75 or less, indicating severe ischemia. Primary end point was incidence of major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, or stroke) at 30 days and 1 year. RESULTS: Coronary CTA and FFRCT was performed in 90 CEA patients (age 67 ± 8 years; male 66%). Lesion-specific coronary ischemia was found in 51 patients (57%) with a mean FFRCT of 0.71 ± 0.14. Severe coronary ischemia was present in 39 patients (43%), 26 patients had multivessel ischemia, and 5 had left main disease. CEA was performed as scheduled in all patients with no postoperative deaths or myocardial infarctions. There were no MACE events at 30 days. After recovery from surgery, 36 patients with significant lesion-specific ischemia underwent coronary angiography with coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) in 30 patients (33%). Survival at 1 year was 100% and freedom from MACE was 98%. CONCLUSIONS: Patients undergoing CEA have a high prevalence of unsuspected (silent) coronary ischemia, which may place them at risk for coronary events. Preoperative diagnosis of silent ischemia using CTA and FFRCT can identify high-risk patients and help to guide patient management. Selective postoperative coronary revascularization of patients with significant ischemia may decrease the risk of cardiac events and improve survival, but longer follow-up is needed and prospective, controlled trials are indicated.

Pre-operative Diagnosis of Silent Coronary Ischaemia May Reduce Post-operative Death and Myocardial Infarction and Improve Survival of Patients Undergoing Lower Extremity Surgical Revascularisation.

OBJECTIVE: Patients undergoing peripheral vascular surgery have increased risk of death and myocardial infarction (MI), which may be due to unsuspected (silent) coronary ischaemia. The aim was to determine whether pre-operative diagnosis of silent ischaemia using coronary computed tomography (CT) derived fractional flow reserve (FFRCT) can facilitate multidisciplinary care to reduce post-operative death and MI, and improve survival. METHODS: This was a single centre prospective study with historic controls. Patients with no cardiac symptoms undergoing lower extremity surgical revascularisation with pre-operative coronary CTA-FFRCT testing were compared with historic controls with standard pre-operative testing. Silent coronary ischaemia was defined as FFRCT ≤ 0.80 distal to coronary stenosis with FFRCT ≤ 0.75 indicating severe ischaemia. End points included cardiovascular (CV) death, MI, and all cause death through one year follow up. RESULTS: There were no statistically significant differences between CT angiography (CTA-FFRCT) (n = 135) and control (n = 135) patients with regard to age (66 ± 8 years), sex, comorbidities, or surgery performed. Coronary CTA showed ≥ 50% stenosis in 70% of patients with left main stenosis in 7%. FFRCT revealed silent coronary ischaemia in 68% of patients with severe ischaemia in 53%. The status of coronary ischaemia was unknown in the controls. At 30 days, CV death and MI in the CTA-FFRCT group were not statistically significantly different from controls (0% vs. 3.7% [p = .060] and 0.7% vs. 5.2% [p = .066], respectively). Post-operative coronary revascularisation was performed in 54 patients to relieve silent ischaemia (percutaneous coronary intervention in 47, coronary artery bypass graft in seven). At one year, CTA-FFRCT patients had fewer CV deaths (0.7% vs. 5.9%; p = .036) and MIs (2.2% vs. 8.1%; p = .028) and improved survival (p = .018) compared with controls. CONCLUSION: Pre-operative diagnosis of silent coronary ischaemia in patients undergoing lower extremity revascularisation surgery can facilitate multidisciplinary patient care with selective post-operative coronary revascularisation. This strategy reduced post-operative death and MI and improved one year survival compared with standard care.

Circulating plasma microRNA-126, microRNA-145, and microRNA-155 and their association with atherosclerotic plaque characteristics.

AIMS: Circulating microRNAs (miRNAs) have been identified as biomarkers for several diseases. Dysregulation of miRNA-126, microRNA-145, and microRNA-155 has been shown to be associated with atherosclerotic lesion formation. The aim of this study was to evaluate the association between atherosclerosis-related miRNAs and unfavorable atherosclerotic plaque characteristics. METHODS AND RESULTS: Forty patients with stable coronary artery disease admitted for elective percutaneous coronary intervention (PCI) were enrolled in a prospective study. After PCI, intravascular ultrasound (IVUS), and iMAP-IVUS analysis were performed to assess the proportion of fibrotic, necrotic, lipidic, and calcific tissue within atherosclerotic plaques. Total RNA was isolated from plasma to evaluate the expression of circulating miRNA-126, miRNA-145, and miRNA-155. Plasma lipid and glucose metabolism-related variables were measured to determine any association with plaque characteristics or miRNA expression. Expression of miRNA-126 was negatively correlated with plaque fibrotic tissue (r=-0.28; P=0.044), while positively correlated with plaque necrotic tissue (r=0.31; P=0.029) and necrolipidic tissue (r=0.31; P=0.031). MiRNA-145 was positively correlated with plaque lipidic (r=0.32; P=0.023) and necrolipidic tissue (r=0.31; P=0.029). Patient age was associated with plaque fibrotic tissue (r=-0.41; P=0.005), necrotic tissue (r=0.33; P=0.022), and lipid content (r=0.33; P=0.022). High-density lipoprotein cholesterol was positively correlated with plaque necrotic (r=0.28; P=0.042) and calcific (r=0.28; P=0.044) tissue volume. Calcific tissue volume was positively correlated with C-peptide (r=0.34; P=0.033). After multivariate logistic regression analysis, both miRNA-126 and miRNA-145 expressions were associated with increased necrolipidic tissue content (ß=0.34; P=0.050; and ß=0.35; P=0.037, respectively). CONCLUSIONS: Expressions of miRNA-126 and miRNA-145 were associated with increased plaque necrolipidic tissue content. RELEVANCE FOR PATIENTS: Although further research is needed to support the study data, miRNA-126 and miRNA-145 may serve as potential plaque vulnerability biomarkers in the future.

Prognostic Value and Risk Continuum of Noninvasive Fractional Flow Reserve Derived from Coronary CT Angiography.

Background Coronary CT angiography with noninvasive fractional flow reserve (FFR) predicts lesion-specific ischemia when compared with invasive FFR. The longer term prognostic value of CT-derived FFR (FFRCT) is unknown. Purpose To determine the prognostic value of FFRCT when compared with coronary CT angiography and describe the relationship of the numeric value of FFRCT with outcomes. Materials and Methods This prospective subanalysis of the NXT study (Clinicaltrials.gov: NCT01757678) evaluated participants suspected of having stable coronary artery disease who were referred for invasive angiography and who underwent FFR, coronary CT angiography, and FFRCT. The incidence of the composite primary end point of death, myocardial infarction, and any revascularization and the composite secondary end point of major adverse cardiac events (MACE: cardiac death, myocardial infarction, unplanned revascularization) were compared for an FFRCT of 0.8 or less versus stenosis of 50% or greater on coronary CT angiograms, with treating physicians blinded to the FFRCT result. Results Long-term outcomes were obtained in 206 individuals (age, 64 years ± 9.5), including 64% men. At median follow-up of 4.7 years, there were no cardiac deaths or myocardial infarctions in participants with normal FFRCT. The incidence of the primary end point was more frequent in participants with positive FFRCT compared with clinically significant stenosis at coronary CT angiography (73.4% [80 of 109] vs 48.7% [91 of 187], respectively; P < .001), with the majority of outcomes being planned revascularization. Corresponding hazard ratios (HRs) were 9.2 (95% confidence interval [CI]: 5.1, 17; P < .001) for FFRCT and 5.9 (95% CI: 1.5, 24; P = .01) for coronary CT angiography. FFRCT was a superior predictor compared with coronary CT angiography for primary end point (C-index FFRCT, 0.76 vs coronary CT angiography, 0.54; P < .001) and MACE (FFRCT, 0.71 vs coronary CT angiography, 0.52; P = .001). Frequency of MACE was higher in participants with positive FFRCT compared with coronary CT angiography (15.6% [17 of 109] vs 10.2% [19 of 187], respectively; P = .02), driven by unplanned revascularization. MACE HR was 5.5 (95% CI: 1.6, 19; P = .006) for FFRCT and 2.0 (95% CI: 0.3, 14; P = .46) for coronary CT angiography. Each 0.05-unit FFRCT reduction was independently associated with greater incidence of primary end point (HR, 1.7; 95% CI: 1.4, 1.9; P < .001) and MACE (HR, 1.4; 95% CI: 1.1, 1.8; P < .001). Conclusion In stable patients referred for invasive angiography, a CT-derived fractional flow reserve (FFRCT) value of 0.8 or less was a predictor of long-term outcomes driven by planned and unplanned revascularization and was superior to clinically significant stenosis on coronary CT angiograms. Additionally, the numeric value of FFRCT was an independent predictor of outcomes. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Dennie and Rubens in this issue.

Two-year clinical outcomes after implantation of an everolimus-eluting bioresorbable scaffold (Absorb) in stable angina and acute coronary syndrome patients. Single-centre real-life registry data.

AIM: The aim of this long-term registry data was to evaluate 2-year clinical and angiographic outcomes after implantation of everolimus-eluting bioresorbable scaffolds (Absorb) from the Latvian Centre of Cardiology Real-life Registry. MATERIAL AND METHODS: Between November 2012 and December 2014 in the Centre of Cardiology Real-life Bioresorbable Vascular Scaffold Registry, 187 patients with stable angina or acute coronary syndrome and available 2-year follow-up were selected. All patients had percutaneous coronary intervention (PCI) following bioresorbable scaffold (Absorb) implantation. At 2 years, clinical parameters were analysed in stable angina and acute coronary syndrome subgroups: all-cause death, cardiac death, non-cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), scaffold thrombosis (ST), cerebral infarction, in-scaffold restenosis and bleeding. RESULTS: The clinical follow-up rate at 2 years was 96.2%. In-hospital death occurred in 2 (1.1%) patients, and 1 (0.5%) patient had in-hospital MI. At 2 years, the rate of all-cause death was 3.9% (n = 7), MI 1.6% (n = 3), TLR 3.9% (n = 7), and TVR 8.4% (n = 15). Between hospital discharge and 2-year follow-up scaffold thrombosis occurred in 2 (1.1%) patients. In-hospital scaffold thrombosis occurred in 1 (0.5%) patient due to clopidogrel resistance, and 1 additional case of scaffold thrombosis occurred at 5 days after implantation (0.5%). CONCLUSIONS: Bioresorbable scaffolds showed acceptable efficacy (target lesion revascularization) and safety (cardiac death, myocardial infarction, and scaffold thrombosis) results at mid-term follow-up in stable angina and acute coronary syndrome patients.

Management of coronary artery disease patients in Latvia compared with practice in Central-Eastern Europe and globally: analysis of the CLARIFY registry.

BACKGROUND AND OBJECTIVE: Management of outpatients with stable coronary artery disease (CAD) is important in secondary prevention. The objective was to describe differences in the characteristics of CAD patients in Latvia compared with other countries. MATERIALS AND METHODS: CLARIFY is an ongoing international, prospective, observational, longitudinal registry of outpatients with CAD. Data regarding treated outpatients with established CAD from the CLARIFY registry in Latvia (n=120) were compared with those from the rest of Central-Eastern Europe (CEE) (n=2888) and worldwide (n=33,163). RESULTS: Patients in Latvia had a larger waist circumference (101 [95-109] vs. 99 [91-106] in CEE, 96.5 [88-105]cm worldwide; P=0.023 and P<0.001, respectively) and higher blood pressure (systolic: 138.28±17.13 vs. 133.77±16.47 in CEE and 130.97±16.65mm Hg worldwide, P=0.003 and P<0.001; diastolic: 82.98±8.58 vs. 80.01±9.61 in CEE and 77.22±9.97mm Hg worldwide, P<0.001 and P<0.001, respectively). Body mass index in Latvia did not differ significantly from that in CEE (P=0.422), but was higher than worldwide (28.8 [26.2-32.0] vs. worldwide 27.3 [24.8-30.3]kg/m(2), P<0.001). The history of percutaneous coronary intervention was more frequent in Latvia (74.17% vs. 59.34% in CEE and 58.61% worldwide, P=0.001 and P<0.001, respectively). Latvian patients more frequently used aspirin (97.50% in Latvia vs. 89.75% in CEE and 87.64% worldwide, P=0.005 and P=0.001, respectively). CONCLUSIONS: Latvian CAD patients are well managed in terms of aspirin use and frequency of percutaneous coronary intervention. Control of obesity and high BP is poorer and needs further improvement.

Insufficient control of heart rate in stable coronary artery disease patients in Latvia.

BACKGROUND AND OBJECTIVE: Heart rate (HR) ≥70 beats per minute (bpm) increases cardiovascular risk in coronary artery disease (CAD) patients. The objective of the analysis is to characterize HR as well as other clinical parameters in outpatients with stable CAD in Latvia. MATERIALS AND METHODS: CLARIFY is an ongoing international registry of outpatients with established CAD. Latvian data regarding 120 patients enrolled in CLARIFY and collected at baseline visit during 2009-2010 were analyzed. RESULTS: The mean HR was 67.7±9.5 and 66.9±10.7bpm when measured by pulse palpation and electrocardiography, respectively. HR ≤60bpm and ≥70bpm was observed in 25% and 35.8% of patients, respectively. When analyzing patients with angina symptoms, 22.8% had HR ≤60bpm while HR ≥70bpm was observed in 33.3% of the cases. HR ≥70bpm was observed in 36.2% of patients with symptoms of chronic heart failure. Beta-blockers were used in 81.7% of the patients. Metoprolol (long acting succinate), bisoprolol, nebivolol and carvedilol in average daily doses 63.8, 5.3, 4.5, and 10.4mg/d were used in 47, 37, 11 and 3 cases, respectively. Among patients with HR ≥70bpm 79.1% were using beta-blockers. Medications did not differ significantly between the three groups according to HR level (≤60, 61-69 and ≥70bpm). CONCLUSIONS: Despite the wide use of beta-blockers, HR is insufficiently controlled in the analyzed sample of stable CAD patients in Latvia. Target HR ≤60bpm is achieved only in 25% of the patients while more than one third have increased HR ≥70bpm.

Use of intravascular imaging in managing coronary artery disease.

For many years, coronary angiography has been considered "the gold standard" for evaluating patients with coronary artery disease. However, angiography only provides a planar two-dimensional silhouette of the lumen and is unsuitable for the precise assessment of atherosclerosis. With the introduction of intravascular imaging, direct visualization of the arterial wall is now feasible. Intravascular imaging modalities extend diagnostic information, thereby enabling more precise evaluation of plaque burden and vessel remodeling. Of all technologies, intravascular ultrasound (IVUS) is the most mature and widely used intravascular imaging technique. Optical coherence tomography (OCT) is an evolving technology that has the highest spatial resolution of existing imaging methods, and it is becoming increasingly widespread. These methods are useful tools for planning interventional strategies and optimizing stent deployment, particularly when stenting complex lesions. We strongly support the mandatory use of IVUS for left main percutaneous coronary intervention (PCI). In addition, it can be used to evaluate vascular responses, including neointimal growth and strut apposition, during follow-ups. Adequately powered randomized trials are needed to support IVUS or OCT use in routine clinical practice and to answer whether OCT is superior to IVUS in reducing adverse events when used to guide PCI. The current perception and adoption of innovative interventional devices, such as bioabsorbable scaffolds, will increase the need for intravascular imaging in the future.

Long-term outcomes of percutaneous coronary interventions or coronary artery bypass grafting for left main coronary artery disease in octogenarians (from a Drug-Eluting stent for LefT main Artery registry substudy).

Percutaneous coronary intervention (PCI) with drug-eluting stents is an accepted alternative to surgery for the treatment of unprotected left main coronary artery (ULMCA) disease, but the long-term outcome in elderly patients is unclear. Aim of our study was to compare the clinical outcomes of octogenarians with ULMCA disease treated either with PCI with drug-eluting stents or coronary artery bypass grafting (CABG). The primary study end point was the composite of death, cerebrovascular accident, and myocardial infarction at follow-up. A total of 304 consecutive patients with ULMCA stenosis treated with PCI or CABG and aged ≥80 years were selected and analyzed in a large multinational registry. Two hundred eighteen were treated with PCI and 86 with CABG. During the hospitalization, a trend toward a higher mortality rate was reported in PCI-treated patients (3.5% vs 7.3%, p = 0.32). At a median follow-up of 1,088 days, the incidence of the primary end point was similar in the 2 groups (32.6% vs 30.2%, p = 0.69). Incidence of target vessel revascularization at follow-up was higher in PCI-treated patients (10% vs 4.2%, p = 0.05). At multivariate analysis, left ventricular ejection fraction was the only independent predictor of the primary end point (hazard ratio 0.95, 95% confidence interval 0.91 to 0.98, p = 0.001). After adjustment with propensity score, the revascularization strategy was not significantly correlated to the incidence of the primary end point (hazard ratio 0.98, 95% confidence interval 0.57 to 1.71, p = 0.95). In octogenarians, no difference was observed in the occurrence of the primary end point after PCI or CABG for the treatment of ULMCA disease. However, the rate of target vessel revascularization was higher in the PCI group.