Serial fractional flow reserve, coronary flow reserve and index of microcirculatory resistance after percutaneous coronary intervention in patients treated for stable angina pectoris assessed with PET.

BACKGROUND: Cardiac 15 O-water PET is a noninvasive method to evaluate epicardial and microvascular dysfunction and further quantitate absolute myocardial blood flow (MBF). AIM: The aim of this study was to assess the impact of revascularization on MBF and myocardial flow reserve (MFR) assessed with 15 O-water PET and invasive flow and pressure measurements. METHODS: In 21 patients with single-vessel disease referred for percutaneous coronary intervention (PCI), serial PET perfusion imaging and fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were performed during PCI and after 3 months. RESULTS: In the affected myocardium, stress MBF and MFR increased significantly from before revascularization to 3 months after revascularization: stress MBF 2.4 ±â€…0.8 vs. 3.2 ±â€…0.8; P  < 0.001 and MFR 2.5 ±â€…0.8 vs. 3.4 ±â€…1.1; P  = 0.004. FFR and CFR increased significantly from baseline to after revascularization and remained stable from after revascularization to 3-month follow-up: FFR 0.64 ±â€…0.20 vs. 0.91 ±â€…0.06 vs. 0.91 ±â€…0.07; P  < 0.001; CFR 2.4 ±â€…1.2 vs. 3.6 ±â€…1.9 vs. 3.6 ±â€…1.9; P  < 0.001, whereas IMR did not change significantly: 30.3 ±â€…22.9 vs. 30.1 ±â€…25.3 vs. 31.9 ±â€…25.2; P  = ns. After revascularization, an increase in stress MBF was associated with an increase in FFR ( r  = 0.732; P  < 0.001) and an increase in MFR ( r  = 0.499; P  = 0.021). IMR measured before PCI was inversely associated with improvement in stress MBF, ( r  = -0.616; P  = 0.004). CONCLUSION: Recovery of myocardial perfusion after PCI was associated with an increase in FFR 3 months after revascularization. Microcirculatory dysfunction was associated with less improvement in myocardial perfusion.

[Нospital outcomes of coronary artery bypass grafting in patients with coronary heart disease with previous percutaneous coronary intervention].

AIM: Evaluation of the frequency hospital cardiovascular events in groups of patients with stable angina who underwent percutaneous coronary interventions (PCI) with stenting of the arteries before coronary bypass surgery, or who did not have previous myocardial revascularization. MATERIALS AND METHODS: The 120 patients with stable angina who underwent routine coronary artery bypass grafting were examined. Group composition: Men 80.8%, age 587.6, duration of coronary heart disease 65.7 years, history of myocardial infarction (MI) 77.5%. Arterial hypertension was present in 92.5%, diabetes mellitus in 12.5% of patients. Multivessel coronary artery disease in 72.5% of patients. 28 (23.4%) patients had previously undergone PCI with stenting of the coronary arteries. The period from PCI to coronary bypass surgery was 2032.6 months. Coronary bypass surgery on-pump was performed in 88.3%, coronary bypass surgery on off-pump in 11.7%. The number of distal anastomoses ranged from 1 to 4. RESULTS: There were no differences in clinical and angiographic indicators, pharmacotherapy, and operation characteristics between the groups of patients who were subjected to or did not have PCI before coronary bypass surgery. There were no differences between the analyzed groups of patients in the frequency of cardiac death (0 and 1.1%, p=0.58), non-fatal MI (3.6% and 9.8%, p=0.29), stroke (0 and 1.1%, p=0.58), acute heart failure (11.7% and 34.8%, p=0.06), the number of patients with paroxysms of atrial fibrillation (28.6% and 17.4%, p=0.94), the proportion of patients with resternotomies (3.6% and 3.3%, p=0.94) and gastrointestinal bleeding (3.6% and 4.3%, p=0.86). CONCLUSION: PCI with coronary artery stenting, prior to coronary bypass surgery, does not affect the frequency of post-operative hospital cardiovascular and hemorrhagic complications.

Ethnicity in Complex High-Risk but Indicated Percutaneous Coronary Intervention Types and Outcomes.

Complex High-risk but indicated Percutaneous coronary interventions (CHiPs) is increasingly common in contemporary practice. However, data on ethnic differences in CHiP types, outcomes, and trends in patients with stable angina are limited; this is pertinent given the population of Black, Asian, and other ethnic minorities (BAME) in Europe is increasing. We conducted a retrospective analysis of CHiP procedures undertaken in patients with stable angina using data obtained from the BCIS (British Cardiovascular Intervention Society) registry (2006 to 2017). CHiP cases were identified and categorized by ethnicity into White and BAME groups. We then performed multivariable regression analysis and propensity score matching to determine adjusted odds ratios (aORs) of in-hospital mortality, major bleeding, and major adverse cardiovascular and cerebral events (MACCEs) in BAME compared with Whites. Of 424,290 procedure records, 105,949 were CHiP (25.0%) (White 89,038 [84%], BAME 16,911 [16%]). BAME patients were younger (median 68.1 vs 70.6 years). Previous coronary artery bypass surgery (33.4% vs 38.3%), followed by chronic total occlusion percutaneous coronary intervention (31.9% vs 32%) were common CHiP variables in both groups. The third common variable was age 80 years and above (23.6%) in White patients and severe vascular calcifications in BAME patients (18.8%). BAME patients had higher rates of diabetes (41.1 vs 23.6%), hypertension (68 vs 66.5%), previous percutaneous coronary intervention (43.7 vs 37.6%), and previous myocardial infarction (44.9 vs 42.5%), (p <0.001 for all). Mortality (aOR 1.1, 95% confidence interval [CI] 0.8 to 1.5) and MACCE (aOR 1.0, 95% CI 0.8 to 1.1) odds were similar among the groups. Bleeding odds (aOR 0.7, 95% CI 0.6 to 0.9) were lower in BAME. In conclusion, CHiP procedures differed among the ethnic groups. BAME patients were younger and had worse cardiometabolic profiles. Similar odds of death and MACCE were seen in BAME compared with their White counterparts. Bleeding odds were 30% lower in the BAME group.

Transitions of Care Among Patients Undergoing Percutaneous Coronary Intervention for Stable Angina: Insights From the Veterans Affairs Clinical Assessment Reporting and Tracking Program.

Background Effective transitions from the procedural to outpatient setting are essential to ensure high-quality cardiovascular care across health care systems, particularly among patients undergoing invasive cardiac procedures. We evaluated the association of postprocedural follow-up visits and antiplatelet prescriptions with clinical outcomes among patients undergoing percutaneous coronary intervention for stable angina at community or Veterans Affairs (VA) hospitals. Methods and Results Patients who actively received care within the VA Healthcare System and underwent percutaneous coronary intervention for stable angina at a community or VA hospital between October 1, 2015, and September 30, 2019, were identified. We compared mortality for patients receiving community or VA care, and among subgroups of community-treated patients by the presence of a postprocedural follow-up visit within 30 days or prescription for antiplatelet (P2Y12) medication within 120 days of the procedure. Among 12 837 patients who survived the first 30 days, 5133 were treated at community hospitals, and 7704 were treated in the VA. Prescriptions for antiplatelet therapy were less common for those treated in the community (85%) compared with the VA at 1 year (95%; hazard ratio [HR], 0.46; 95% CI, 0.44-47). Compared with VA-treated patients, the hazards for death were similar for patients treated in the community with a follow-up visit (HR, 1.17; 95% CI, 0.97-1.40) or with a fill for an antiplatelet therapy (HR, 1.08; 95% CI, 0.90-1.30). However, patients treated in the community without a follow-up visit had an 86% (HR, 1.86; 95% CI, 1.40-2.48) increased hazard of death, and those without antiplatelet prescription fill had a 144% increased hazard of death (HR, 2.44; 95% CI, 1.85-3.21) compared with all VA-treated patients. Conclusions Patients treated at community facilities have a decreased chance of receiving antiplatelet prescriptions after percutaneous coronary intervention with a concordant increased hazard of mortality, emphasizing the importance of transitions of care across health care systems when assessing cardiovascular quality.

Quality of Life Assessment in Trials of Revascularization for Chronic Stable Angina: Insights from ORBITA and the Implications of Blinding.

The main aims of therapy in chronic stable angina are to reduce the risk of myocardial infarction and death and improve symptoms and quality of life (QoL). Unblinded trials have shown that revascularization does not reduce the risk of myocardial infarction or death but does appear to improve symptoms. However, symptoms are susceptible to the placebo effect which can bias therapies to appear more effective than they are. To assess the true physical impact of a treatment on symptoms, placebo-controlled trials with patients and medical and research teams blinded to treatment allocation are necessary. Symptoms and QoL can be reported directly by the patient or indirectly by the physician. Patient-reported outcome measures in angina trials can include angina frequency, frequency of nitrate use, exercise capacity, and questionnaires such as the Seattle Angina Questionnaire (SAQ) and the generic EuroQOL-5D-5L (EQ-5D-5L) QoL questionnaire. Physician-assessed outcome measures include Canadian Cardiovascular Society Class. The Objective Randomised Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) trial was the first blinded placebo-controlled study investigating the role of percutaneous coronary intervention (PCI) in chronic stable angina. The trial showed a smaller than expected and not statistically significant effect of placebo-controlled PCI on the primary endpoint of change in exercise time at 6 weeks follow-up in single-vessel coronary artery disease. There was also no significant placebo-controlled treatment effect of PCI for the prespecified secondary endpoints of SAQ or EQ-5D-5L, although PCI did result in 20% more patients becoming free from angina than placebo in a non-prespecified secondary analysis. ORBITA has demonstrated the need for symptomatic and QoL effects of PCI to be studied using placebo control. Here, we describe ways of measuring QoL, the impact of the unblinded and blinded trials to date, what we have learned from ORBITA, and what is next for this common and complex condition.

International Observational Analysis of Evolution and Outcomes of Chronic Stable Angina: The Multinational CLARIFY Study.

BACKGROUND: Although angina is common in patients with stable coronary artery disease, limited data are available on its prevalence, natural evolution, and outcomes in the era of effective cardiovascular drugs and widespread use of coronary revascularization. METHODS: Using data from 32 691 patients with stable coronary artery disease from the prospective observational CLARIFY registry (Prospective Observational Longitudinal Registry of Patients with Stable Coronary Artery Disease), anginal status was mapped each year in patients without new coronary revascularization or new myocardial infarction. The use of medical interventions in the year preceding angina resolution was explored. The effect of 1-year changes in angina status on 5-year outcomes was analyzed using multivariable analysis. RESULTS: Among 7212 (22.1%) patients who reported angina at baseline, angina disappeared (without coronary revascularization) in 39.6% at 1 year, with further annual decreases. In patients without angina at baseline, 2.0% to 4.8% developed angina each year. During 5-year follow-up, angina was controlled in 7773 patients, in whom resolution of angina was obtained with increased use of antianginal treatment in 11.1%, with coronary revascularization in 4.5%, and without any changes in medication or revascularization in 84.4%. Compared to patients without angina at baseline and 1 year, persistence of angina and occurrence of angina at 1 year with conservative management were each independently associated with higher rates of cardiovascular death or myocardial infarction (adjusted hazard ratio, 1.32 [95% CI, 1.12-1.55] for persistence of angina; adjusted hazard ratio, 1.37 [95% CI, 1.11-1.70] for occurrence of angina) at 5 years. Patients whose angina had resolved at 1 year with conservative management were not at higher risk of cardiovascular death or myocardial infarction than those who never experienced angina (adjusted hazard ratio, 0.97 [95% CI, 0.82-1.15]). CONCLUSIONS: Angina affects almost one-quarter of patients with stable coronary artery disease but resolves without events or coronary revascularization in most patients. Resolution of angina within 1 year with conservative management predicted outcomes similar to lack of angina, whereas persistence or occurrence was associated with worse outcomes. Because most patients with angina are likely to experience resolution of symptoms, and because there is no demonstrated outcome benefit to routine revascularization, this study emphasizes the value of conservative management of stable coronary artery disease. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN43070564.

Estimating the real-world performance of the PROMISE minimal-risk tool.

BACKGROUND: Stable chest pain is a common indication for cardiac catheterization. We assessed the prognostic value of the Prospective Multicenter Imaging Study for Evaluation (PROMISE) Minimal-Risk Tool in identifying patients who are at very low risk of obstructive coronary artery disease (CAD) or downstream cardiovascular adverse outcomes. METHODS: We applied the PROMISE Minimal-Risk Tool to consecutive patients without known CAD who underwent elective cardiac catheterization for stable angina from January 1, 2000 to December 31, 2014 in the Duke Databank for Cardiovascular Disease (DDCD). Patients with scores >0.46 (top decile of lowest-risk from the PROMISE cohort) were classified as low-risk. Logistic regression modeling compared likelihood of freedom from obstructive coronary artery disease on index angiography, 2-year survival, and 2-year survival free of myocardial infarction (MI) and MI/revascularization between low- and non low-risk patients. Alternative cut points to define low- risk patients were also explored. RESULTS: Among 6251 patients undergoing cardiac catheterization for stable chest pain, 1082 (17.3%) were low-risk per the PROMISE minimal-risk tool. Among low risk patients, obstructive coronary artery disease was observed in 14.9% and left main disease (≥ 50% Stenosis) was rare (0.9%). Compared with other patients, low risk patients had a higher likelihood of freedom from obstructive coronary disease on index catheterization (85.1% vs. 44.2%, OR 4.84, 95% CI 4.06-5.77). Low risk patients had significantly higher survival (98.2% vs. 94.4%, OR 3.18, 95% CI 1.99-5.08), MI-free survival (97.2% vs. 91.9%, OR 3.03, 95% CI 2.07-4.45), and MI/revascularization-free survival (86.2 vs. 59.9%, OR 4.19, 95% CI 3.48-5.05) at 2 years than non-low risk patients. Operating characteristics for predicting the outcomes of interest varied modestly depending on the low-risk cut-point used but the positive predictive value for 2 year freedom from death was >98% regardless. CONCLUSION: The PROMISE minimal-risk tool identifies 17% of stable chest pain patients referred to cardiac catheterization as low risk. These patients have a low prevalence of obstructive CAD and better survival than non-low risk patients. While this suggests that these patients are unlikely to benefit from catheterization, further research is needed to confirm a favorable downstream prognosis with medical management alone.

Four-year outcomes after percutaneous coronary intervention of unprotected left main coronary artery disease in patients with stable angina and acute coronary syndrome.

Background. Percutaneous coronary intervention (PCI) of unprotected left main coronary artery disease (ULMCAD) have become a feasible and efficient alternative to coronary artery bypass surgery, especially in patients with acute coronary syndrome (ACS). There are limited data regarding early and late outcomes after ULMCAD PCI in patients with ACS and stable angina.The aim of this study was to compare early and four-year clinical outcomes in patients with ULMCAD PCI presenting as ACS or stable angina in a high-volume PCI center.Methods. We conducted a single center retrospective observational study, which included 146 patients with ULMCAD undergoing PCI between 2014 and 2018. Patients were divided in two groups: Group A included patients with stable angina (n = 70, 47.9%) and Group B patients with ACS (n = 76, 52.1%).Results. 30-day mortality was 8.22% overall, lower in Group A (1.43% vs 14.47%, p = 0.02). Mortality and major adverse cardiac events (MACE) rates at 4 years were significantly lower in Group A (9.64% vs 33.25%, p = 0.001, and 24.06% vs 40.11%, p = 0.012, respectively). Target lesion revascularization (TLR) at 4 year did not differ between groups (15% in Group A vs 12.76% in Group B, p = 0.5).Conclusions. In our study patients with ULMCAD and ACS undergoing PCI had higher early and long-term mortality and MACE rates compared to patients with stable angina, with similar TLR rate at 4-year follow-up.

Traditional Chinese Medicine in the prevention and treatment of stable angina pectoris in patients with coronary heart disease based on the theory of "phlegm and blood stasis" under guidance of evidence-based medicine: a prospective cohort study.

OBJECTIVE: To ascertain whether continuous treatment with Traditional Chinese Medicine (TCM) combined with standardized drug therapy from Western Medicine can further reduce the incidence of cardiovascular events in patients with coronary heart disease and angina and reduce the incidence of angina pectoris in patients with coronary heart disease. METHODS: A multicenter, prospective cohort study of 1042 patients in 22 hospitals was conducted. A total of 423 patients with angina pectoris were treated with standardized Western Medicine alone (control group) and 619 with a combination of Chinese and Western Medicine (exposure group). The two groups underwent follow-up for 1 year to establish whether there was any improvement in the incidence of cardiovascular events or change in the curative effect. RESULTS: The incidence of primary endpoint events in the combined-exposure group decreased by 0.45% (P > 0.05) and the incidence of secondary terminal events decreased by 5.25% in comparison with the control group (P < 0.05). The total angina pectoris score clearly decreased in the Western Medicine group over the first 6 months, but the decline was more apparent in the combined-exposure group. CONCLUSION: Compared with treatment using standardized Western Medicine alone, providing TCM combined with Western medical treatment reduced the incidence of cardiovascular events in patients with stable angina pectoris (grade Ⅱ endpoint) and effectively improved the curative effect.

Circulating hepassocin level in patients with stable angina is associated with fatty liver and renal function.

Background: Chronic kidney disease (CKD) is a major risk factor for coronary artery disease and it is often associated with hepatic steatosis. Hepassocin (also known as hepatocyte-derived fibrinogen related protein or fibrinogen-like 1) is a novel hepatokine that causes hepatic steatosis and induces insulin resistance. However, the role of hepassocin in renal function status remains unclear. Our objective was to investigate the association of plasma hepassocin level with fatty liver and renal function status in patients with stable angina. Methods: Plasma hepassocin levels were determined by enzyme-linked immunosorbent assays in 395 consecutive patients with stable angina. Renal function was defined as an estimated glomerular filtration rate (eGFR). Fatty liver was defined by ultrasonography and fibrosis-4 (FIB-4) index. Results: With increasing hepassocin tertiles, patients had higher prevalence of fatty live, an increased waist-to-hip ratio, and neutrophil count, monocyte count, and FIB-4 index, higher levels of uric acid, blood urine nitrogen and higher sensitivity C-reactive protein. They also had incrementally lower eGFR, serum hemoglobin and albumin levels. In multiple linear stepwise regression analysis, only eGFR was significantly independent negatively associated with plasma hepassocin levels. Conclusion: Our results indicate that circulating hepassocin in patients with stable angina is associated with fatty liver and renal function, which suggests that increased plasma hepassocin may be involved in the pathogenesis of fatty liver and CKD.

Clinical effectiveness and safety of salvia miltiorrhiza depside salt combined with aspirin in patients with stable angina pectoris: A multicenter, pragmatic, randomized controlled trial.

BACKGROUND: Salvia Miltiorrhiza Depside Salt (SMDS) was extracted from Salvia miltiorrhiza with high-quality control of active principles. In 2005, China's FDA approved the use of SMDS for stable angina pectoris (SAP), but the evidence of SMDS combined with aspirin remains unclear. PURPOSE: The aim of this study was to assess the clinical effectiveness and safety of SMDS combined with aspirin in patients with SAP. METHODS: A multicenter, pragmatic, three-armed parallel group and an individually randomized controlled superiority trial was designed. Participants aged 35 to 75 years old with SAP were recruited from four "Class Ⅲ Grade A" hospitals in China. Participants who were randomized into the SMDS group were treated with SMDS by intravenous drip. Participants in the control group received aspirin enteric-coated tablets (aspirin). Participants who were randomly assigned to the combination group received SMDS combined with aspirin. All participants received standard care from clinicians, without any restrictions. The primary outcome measure was thromboelastography (TEG). Secondary outcome measures included symptom score of the Seattle Angina Questionnaire (SAQ), visual analogue scale (VAS) score of traditional Chinese medicine (TCM) symptoms, platelet aggregation measured by light transmittance aggregometry (LTA), and fasting blood glucose. Effectiveness evaluation data were collected at baseline and ten days after treatment. Researchers followed up with participants for one month after treatment to determine whether adverse events (AEs) or adverse drug reactions (ADRs) such as bleeding tendency occurred. All statistical calculations were carried out with R 3.5.3 statistical analysis software. RESULTS: A total of 135 participants completed follow-up data on the primary outcome after ten days of treatment. Participants in the SMDS combined aspirin group had the highest improvement rate of sensitivity in AA% [p < 0.001, 95% CI (0.00-0.00)], from 30.6% before treatment to 81.6% after treatment. Participants with drug resistance (AA% < 20%) in the SMDS combined with aspirin group also had the highest sensitivity rate [p < 0.001, 95% CI (0.00-0.00)] after treatment (accounting for 81.0% of the combination group and 60.7% of the sensitive participants). The improvement of TCM symptoms in participants treated with SMDS combined with aspirin was significantly better than that of the aspirin group [MD = 1.71, 95% CI (0.15-3.27), p = 0.032]. There were no significant differences in other indexes (R, TPI, MA, K, CI, α value) of TEG, SAQ, platelet aggregation and fasting blood glucose among the three groups. No bleeding tendency or ADRs occurred in all participants. CONCLUSION: SMDS combined with aspirin is a clinically effective and safe intervention to treat adults aged 35 and older with SAP. This trial shows that SMDS combined with aspirin can significantly improve the sensitivity rate of AA% in TEG and the VAS score of TCM symptoms. Further large samples and high-quality research are needed to determine if certain participants might benefit more from SMDS combined with aspirin. The study protocol was registered in the Clinical Trials USA registry (registration No. NCT02694848).

Exercise Electrocardiography and Computed Tomography Coronary Angiography for Patients With Suspected Stable Angina Pectoris: A Post Hoc Analysis of the Randomized SCOT-HEART Trial.

Importance: Recent European guidance supports a diminished role for exercise electrocardiography (ECG) in the assessment of suspected stable angina. Objective: To evaluate the utility of exercise ECG in contemporary practice and assess the value of combined functional and anatomical testing. Design, Setting, and Participants: This is a post hoc analysis of the Scottish Computed Tomography of the Heart (SCOT-HEART) open-label randomized clinical trial, conducted in 12 cardiology chest pain clinics across Scotland for patients with suspected angina secondary to coronary heart disease. Between November 18, 2010, and September 24, 2014, 4146 patients aged 18 to 75 years with stable angina underwent clinical evaluation and 1417 of 1651 (86%) underwent exercise ECG prior to randomization. Statistical analysis was conducted from October 10 to November 5, 2019. Interventions: Patients were randomized in a 1:1 ratio to receive standard care plus coronary computed tomography (CT) angiography or to receive standard care alone. The present analysis was limited to the 3283 patients who underwent exercise ECG alone or in combination with coronary CT angiography. Main Outcomes and Measures: The primary clinical end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years. Results: Among the 3283 patients (1889 men; median age, 57.0 years [interquartile range, 50.0-64.0 years]), exercise ECG had a sensitivity of 39% and a specificity of 91% for detecting any obstructive coronary artery disease in those who underwent subsequent invasive angiography. Abnormal results of exercise ECG were associated with a 14.47-fold (95% CI, 10.00-20.41; P < .001) increase in coronary revascularization at 1 year and a 2.57-fold (95% CI, 1.38-4.63; P < .001) increase in mortality from coronary heart disease death at 5 years or in cases of nonfatal myocardial infarction at 5 years. Compared with exercise ECG alone, results of coronary CT angiography had a stronger association with 5-year coronary heart disease death or nonfatal myocardial infarction (hazard ratio, 10.63; 95% CI, 2.32-48.70; P = .002). The greatest numerical difference in outcome with CT angiography compared with exercise ECG alone was observed for those with inconclusive results of exercise ECG (5 of 285 [2%] vs 13 of 283 [5%]), although this was not statistically significant (log-rank P = .05). Conclusions and Relevance: This study suggests that abnormal results of exercise ECG are associated with coronary revascularization and the future risk of adverse coronary events. However, coronary CT angiography more accurately detects coronary artery disease and is more strongly associated with future risk compared with exercise ECG. Trial Registration: ClinicalTrials.gov Identifier: NCT01149590.

Comparison of Instantaneous Wave-Free Ratio (iFR) and Fractional Flow Reserve (FFR) with respect to Their Sensitivities to Cardiovascular Factors: A Computational Model-Based Study.

While coronary revascularization strategies guided by instantaneous wave-free ratio (iFR) are, in general, noninferior to those guided by fractional flow reserve (FFR) with respect to the rate of major adverse cardiac events at one-year follow-up in patients with stable angina or an acute coronary syndrome, the overall accuracy of diagnosis with iFR in large patient cohorts is about 80% compared with the diagnosis with FFR. So far, it remains incompletely understood what factors contribute to the discordant diagnosis between iFR and FFR. In this study, a computational method was used to systemically investigate the respective effects of various cardiovascular factors on FFR and iFR. The results showed that deterioration in aortic valve disease (e.g., regurgitation or stenosis) led to a marked decrease in iFR and a mild increase in FFR given fixed severity of coronary artery stenosis and that increasing coronary microvascular resistance caused a considerable increase in both iFR and FFR, but the degree of increase in iFR was lower than that in FFR. These findings suggest that there is a high probability of discordant diagnosis between iFR and FFR in patients with severe aortic valve disease or coronary microcirculation dysfunction.

Artificial Intelligence Uncovered Clinical Factors for Cardiovascular Events in Myocardial Infarction Patients with Glucose Intolerance.

PURPOSE: Glucose intolerance (GI), defined as either prediabetes or diabetes, promotes cardiovascular events in patients with myocardial infarction (MI). Using the pooled clinical data from patients with MI and GI in the completed ABC and PPAR trials, we aimed to identify their clinical risk factors for cardiovascular events. METHODS: Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 415,328 combinations of < 4 clinical parameters. RESULTS: We identified 242 combinations that predicted the occurrence of hospitalization for (1) percutaneous coronary intervention for stable angina, (2) non-fatal MI, (3) worsening of heart failure (HF), and (4) all causes, and we analyzed combinations in 1476 patients. Among these parameters, the use of proton pump inhibitors (PPIs) or plasma glucose levels > 200 mg/dl after 2 h of a 75 g oral glucose tolerance test were linked to the coronary events of (1, 2). Plasma BNP levels > 200 pg/dl were linked to coronary and cardiac events of (1, 2, 3). Diuretics use, advanced age, and lack of anti-dyslipidemia drugs were linked to cardiovascular events of (1, 3). All of these factors were linked to (4). Importantly, each finding was verified by independently drawn Kaplan-Meier curves, indicating that the determined factors accurately affected cardiovascular events. CONCLUSIONS: In most previous MI patients with GI, progression of GI, PPI use, or high plasma BNP levels were linked to the occurrence of coronary stenosis or recurrent MI. We emphasize that use of AI may comprehensively uncover the hidden risk factors for cardiovascular events.

Low-Attenuation Noncalcified Plaque on Coronary Computed Tomography Angiography Predicts Myocardial Infarction: Results From the Multicenter SCOT-HEART Trial (Scottish Computed Tomography of the HEART).

BACKGROUND: The future risk of myocardial infarction is commonly assessed using cardiovascular risk scores, coronary artery calcium score, or coronary artery stenosis severity. We assessed whether noncalcified low-attenuation plaque burden on coronary CT angiography (CCTA) might be a better predictor of the future risk of myocardial infarction. METHODS: In a post hoc analysis of a multicenter randomized controlled trial of CCTA in patients with stable chest pain, we investigated the association between the future risk of fatal or nonfatal myocardial infarction and low-attenuation plaque burden (% plaque to vessel volume), cardiovascular risk score, coronary artery calcium score or obstructive coronary artery stenoses. RESULTS: In 1769 patients (56% male; 58±10 years) followed up for a median 4.7 (interquartile interval, 4.0-5.7) years, low-attenuation plaque burden correlated weakly with cardiovascular risk score (r=0.34; P<0.001), strongly with coronary artery calcium score (r=0.62; P<0.001), and very strongly with the severity of luminal coronary stenosis (area stenosis, r=0.83; P<0.001). Low-attenuation plaque burden (7.5% [4.8-9.2] versus 4.1% [0-6.8]; P<0.001), coronary artery calcium score (336 [62-1064] versus 19 [0-217] Agatston units; P<0.001), and the presence of obstructive coronary artery disease (54% versus 25%; P<0.001) were all higher in the 41 patients who had fatal or nonfatal myocardial infarction. Low-attenuation plaque burden was the strongest predictor of myocardial infarction (adjusted hazard ratio, 1.60 (95% CI, 1.10-2.34) per doubling; P=0.014), irrespective of cardiovascular risk score, coronary artery calcium score, or coronary artery area stenosis. Patients with low-attenuation plaque burden greater than 4% were nearly 5 times more likely to have subsequent myocardial infarction (hazard ratio, 4.65; 95% CI, 2.06-10.5; P<0.001). CONCLUSIONS: In patients presenting with stable chest pain, low-attenuation plaque burden is the strongest predictor of fatal or nonfatal myocardial infarction. These findings challenge the current perception of the supremacy of current classical risk predictors for myocardial infarction, including stenosis severity. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01149590.

Correlation of plasma soluble suppression of tumorigenicity-2 level with the severity and stability of coronary atherosclerosis.

BACKGROUND: Soluble growth stimulation expressed gene 2 (sST2) is the receptor of interleukin (IL)-33. We hypothesized the IL-33/ST2 pathway may be closely related to the progression of coronary atherosclerotic lesions. METHODS: We analyzed 262 patients, including 63 with stable angina pectoris (SAP), 97 with acute coronary syndrome (ACS), and 102 control subjects. Plasma sST2 levels were determined using ELISA. Gensini scores were calculated. Patients with ACS and SAP were further divided according to the complexity of atherosclerotic lesions (simple/complex). Statistical analysis was performed on all data. RESULTS: The plasma sST2 levels were significantly higher in patients with coronary artery disease (CAD) than in the control group, and were significantly higher in ACS patients with complex lesions than in those with simple lesions. There were no correlations between plasma sST2 level and both the number of culprit vessels and Gensini score. Multivariate stepwise regression analysis revealed that angiographically detected complex lesions were independently correlated with plasma sST2 level. Logistic regression analyses showed that sST2 was an independent factor of both CAD and the lesion type (simple/complex) of ACS. For the diagnosis of ACS and complex lesions, the area under the receiver operating characteristic curve of sST2 was 0.651. CONCLUSIONS: The plasma sST2 level was not correlated with the stenosis severity of coronary atherosclerosis. A relationship between the plasma sST2 level and the morphology of complex lesions was found for the first time, especially in ACS patients. It may be a new marker for assessing the stability and complexity of atherosclerotic plaques.

Validation of European Society of Cardiology pre-test probabilities for obstructive coronary artery disease in suspected stable angina.

AIMS: To assess contemporary pre-test probability estimates for obstructive coronary artery disease in patients with stable chest pain. METHODS AND RESULTS: In this substudy of a multicentre randomized controlled trial, we compared 2019 European Society of Cardiology (ESC)-endorsed pre-test probabilities with observed prevalence of obstructive coronary artery disease on computed tomography coronary angiography (CTCA). We assessed associations between pre-test probability, 5-year coronary heart disease death or non-fatal myocardial infarction and study intervention (standard care vs. CTCA). The study population consisted of 3755 patients (30-75 years, 46% women) with a median pre-test probability of 11% of whom 1622 (43%) had a pre-test probability of >15%. In those who underwent CTCA (n = 1613), the prevalence of obstructive disease was 22%. When divided into deciles of pre-test probability, the observed disease prevalence was similar but higher than the corresponding median pre-test probability [median difference 2.3 (1.3-5.6)%]. There were more clinical events in patients with a pre-test probability >15% compared to those at 5-15% and <5% (4.1%, 1.5%, and 1.4%, respectively, P < 0.001). Across the total cohort, fewer clinical events occurred in patients who underwent CTCA, with the greatest difference in those with a pre-test probability >15% (2.8% vs. 5.3%, log rank P = 0.01), although this interaction was not statistically significant on multivariable modelling. CONCLUSION: The updated 2019 ESC guideline pre-test probability recommendations tended to slightly underestimate disease prevalence in our cohort. Pre-test probability is a powerful predictor of future coronary events and helps select those who may derive the greatest absolute benefit from CTCA.

Combined Vascular Brachytherapy and Stenting for the Treatment of In-Stent Restenosis.

In-stent restenosis (ISR) remains a therapeutic challenge in the current drug-eluting stent (DES) era. Vascular brachytherapy (VBT) is a therapeutic option for ISR, but data about the outcomes of combination therapy with VBT and stenting for ISR lesions are sparse. We retrospectively analyzed patients who presented with ISR at our institution from 2003 through 2017. Three treatment arms were compared: VBT alone, VBT plus bare-metal stent (BMS), and VBT plus DES. Clinical, procedural, and 1-year outcome data were collected. Follow-up was obtained by phone calls and clinic visits. The patient cohort included 461 patients (764 ISR lesions). Of these, 333 patients (533 lesions) were treated with VBT alone, 89 patients (158 lesions) with VBT plus BMS, and 39 patients (73 lesions) with VBT plus DES. There were no significant differences in baseline characteristics among the 3 groups except for more patients with a remote smoking history in the VBT plus BMS (43.8%) and VBT plus DES groups (56.4%), and more patients with history of peripheral vascular disease (39.5%) and congestive heart failure (27%) in the VBT plus DES group. The most common clinical presentation was unstable angina (64.6%). In the VBT plus DES group, 10.3% of patients presented with MI, versus 5.5% in the VBT alone group and 2.2% in the VBT plus BMS group. At 1-year follow-up, the VBT plus DES group had higher rates of target vessel revascularization-major adverse cardiovascular events (38.5%) than the VBT plus BMS (21.3%) and VBT alone (15.6%) groups (p = 0.002). In conclusion, in patients with ISR, combination therapy with VBT and stenting at the same setup is associated with worse outcomes at 12 months and, if possible, should be avoided.

Feasibility and Clinical Significance of In Vivo Cholesterol Crystal Detection Using Optical Coherence Tomography.

OBJECTIVE: Cholesterol crystals (CCs) are frequently found at the site of acute myocardial infarctions (AMIs), but the role of CCs in the onset of AMI remains unclear due to the lack of validated in vivo imaging tools. The aim of this study was to validate the ability of optical coherence tomography (OCT) to detect CCs and to compare the prevalence and distribution of CCs in patients with AMIs and stable angina pectoris. Approach and Results: CC assessment using OCT were compared with histopathology results in 45 coronary samples. We investigated 152 consecutive patients with AMIs and 41 patients with single vessel-diseased stable angina pectoris. Based on the presence of plaque ruptures (PR), AMI patients were divided into 2 groups: those with PR (n=112) and those without PR (n=40). CCs invading fibrous caps were defined as superficial-type CCs. A multivariable logistic regression analysis was performed to determine PR predictors. The sensitivity and specificity of OCT for detecting CCs were 68% and 92%, respectively. The prevalence of plaques with CCs was higher in the AMI with PR group (AMI with PR 81%, AMI without PR 48%, stable angina pectoris 39%, P<0.01). A multivariable logistic model showed that superficial-type CCs and thin-cap fibroatheromas were positive predictors for PR. CONCLUSIONS: OCT has a high specificity and modest sensitivity for the detection of CCs. The combination of CCs invading fibrous cap and thin-cap fibroatheromas detected by OCT may better identify rupture-prone plaques.

Single Sheath for Dual Injection Prior to CTO Intervention.

To our knowledge, this is the first reported case of a dual injection using a single sheath approach, in order to evaluate a CTO and plan a future intervention.