A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina.

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina. RESULTS: A total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group. CONCLUSIONS: Among patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.).

Coronary sinus reducer for the treatment of refractory angina (ORBITA-COSMIC): a randomised, placebo-controlled trial.

BACKGROUND: The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement. METHODS: ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov, NCT04892537, and completed. FINDINGS: Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77-1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI -0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group. INTERPRETATION: ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease. FUNDING: Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation.

In adults with stable angina, PCI vs. a placebo procedure reduced angina symptoms at 12 wk.

SOURCE CITATION: Rajkumar CA, Foley MJ, Ahmed-Jushuf F, et al; ORBITA-2 Investigators. A placebo-controlled trial of percutaneous coronary intervention for stable angina. N Engl J Med. 2023;389:2319-2330. 38015442.

Gut microbiota and metabolomics profiles in patients with chronic stable angina and acute coronary syndrome.

Cardiovascular disease (CVD) is the leading cause of death worldwide. The gut microbiota and its associated metabolites may be involved in the development and progression of CVD, although the mechanisms and impact on clinical outcomes are not fully understood. This study investigated the gut microbiome profile and associated metabolites in patients with chronic stable angina (CSA) and acute coronary syndrome (ACS) compared with healthy controls. Bacterial alpha diversity in stool from patients with ACS or CSA was comparable to healthy controls at both baseline and follow-up visits. Differential abundance analysis identified operational taxonomic units (OTUs) assigned to commensal taxa differentiating patients with ACS from healthy controls at both baseline and follow-up. Patients with CSA and ACS had significantly higher levels of trimethylamine N-oxide compared with healthy controls (CSA: 0.032 ± 0.023 mmol/L, P < 0.01 vs. healthy, and ACS: 0.032 ± 0.023 mmol/L, P = 0.02 vs. healthy, respectively). Patients with ACS had reduced levels of propionate and butyrate (119 ± 4 vs. 139 ± 5.1 µM, P = 0.001, and 14 ± 4.3 vs. 23.5 ± 8.1 µM, P < 0.001, respectively), as well as elevated serum sCD14 (2245 ± 75.1 vs. 1834 ± 45.8 ng/mL, P < 0.0001) and sCD163 levels (457.3 ± 31.8 vs. 326.8 ± 20.7 ng/mL, P = 0.001), compared with healthy controls at baseline. Furthermore, a modified small molecule metabolomic and lipidomic signature was observed in patients with CSA and ACS compared with healthy controls. These findings provide evidence of a link between gut microbiome composition and gut bacterial metabolites with CVD. Future time course studies in patients to observe temporal changes and subsequent associations with gut microbiome composition are required to provide insight into how these are affected by transient changes following an acute coronary event.NEW & NOTEWORTHY The study found discriminative microorganisms differentiating patients with acute coronary syndrome (ACS) from healthy controls. In addition, reduced levels of certain bacterial metabolites and elevated sCD14 and sCD163 were observed in patients with ACS compared with healthy controls. Furthermore, modified small molecule metabolomic and lipidomic signatures were found in both patient groups. Although it is not known whether these differences in profiles are associated with disease development and/or progression, the findings provide exciting options for potential new disease-related mechanism(s) and associated therapeutic target(s).

Feasibility of double-blinded, placebo-controlled interventional study for assessing catheter ablation efficacy in persistent atrial fibrillation: Insights from the ORBITA AF feasibility study.

BACKGROUND: To date, there are no randomized, double-blinded clinical trials comparing catheter ablation to DC cardioversion (DCCV) with medical therapy in patients with persistent atrial fibrillation (PersAF). Conducting a large-scale trial to address this question presents considerable challenges, including recruitment, blinding, and implementation. We conducted a pilot study to evaluate the feasibility of conducting a definitive placebo-controlled trial. METHODS: This prospective trial was carried out at Barts Heart Centre, United Kingdom, employing a randomized, double-blinded, placebo-controlled design. Twenty patients with PersAF (duration <2 years) were recruited, representing 10% of the proposed larger trial as determined by a power calculation. The patients were randomized in a 1:1 ratio to receive either PVI ± DCCV (PVI group) or DCCV + Placebo (DCCV group). The primary endpoint of this feasibility study was to evaluate patient blinding. Patients remained unaware of their treatment allocation until end of study. RESULTS: During the study, 35% of patients experienced recurrence of PersAF prior to completion of 12 months follow-up. Blinding was successfully maintained amongst both patients and medical staff. The DCCV group had a trend to higher recurrence and repeat procedure rate compared to the PVI group (recurrence of PersAF 60% vs 30%; p = .07 and repeat procedure 70% vs 40%; p = .4). The quality of life experienced by individuals in the PVI group showed improvement, as evidenced by enhanced scores on the AF specific questionnaire (AF PROMS) (3 [±4] vs 21 [±8]) and SF-12 mental-component raw score (51.4 [±7] vs 43.24 [±15]) in patients who maintained sinus rhythm at 12 months. CONCLUSION: This feasibility study establishes the potential for conducting a blinded, placebo-controlled trial to evaluate the efficacy of PVI versus DCCV in patients with PersAF.

Association between dietary macronutrient composition and plasma one-carbon metabolites and B-vitamin cofactors in patients with stable angina pectoris.

Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analysed 1928 patients with suspected stable angina pectoris (geometric mean age 61), representing elevated CVD risk, to assess associations between dietary macronutrient composition (FFQ) and plasma one-carbon metabolites and related B-vitamin status markers (GC-MS/MS, LC-MS/MS or microbiological assay). Diet-metabolite associations were modelled on the continuous scale, adjusted for age, sex, BMI, smoking, alcohol and total energy intake. Average (geometric mean (95 % prediction interval)) intake was forty-nine (38, 63) energy percent (E%) from carbohydrate, thirty-one (22, 45) E% from fat and seventeen (12, 22) E% from protein. The strongest associations were seen for higher protein intake, i.e. with higher plasma pyridoxal 5'-phosphate (PLP) (% change (95 % CI) 3·1 (2·1, 4·1)), cobalamin (2·9 (2·1, 3·7)), riboflavin (2·4 (1·1, 3·7)) and folate (2·1 (1·2, 3·1)) and lower total homocysteine (tHcy) (-1·4 (-1·9, -0·9)) and methylmalonic acid (MMA) (-1·4 (-2·0, -0·8)). Substitution analyses replacing MUFA or PUFA with SFA demonstrated higher plasma concentrations of riboflavin (5·0 (0·9, 9·3) and 3·3 (1·1, 5·6)), tHcy (2·3 (0·7, 3·8) and 1·3 (0·5, 2·2)) and MMA (2·0 (0·2, 3·9) and 1·7 (0·7, 2·7)) and lower PLP (-2·5 (-5·3, 0·3) and -2·7 (-4·2, -1·2)). In conclusion, a higher protein intake and replacing saturated with MUFA and PUFA were associated with a more favourable metabolic phenotype regarding metabolites associated with CVD risk.

E-selectin is associated with stable angina and myocardial infarction in a sample of Kurdish population.

Endothelial dysfunction is the main factor that causes the onset of CAD. Leukocyte adhesion to the endothelium of the active blood artery wall has been demonstrated to be one of the early indicators of arteriosclerosis. This process is regulated by selectins. The purpose of this study is to ascertain the relationship between the polymorphisms in the E-selectin gene that have been linked to ischemic heart disease. We looked at the functional impact of the E-selectin gene polymorphism 7170G>C in Iraqi patients with IHD. This study was conducted on 200 participants who were admitted to the surgical specialty hospital-cardiac center in Erbil City, Iraq between October 2021 and May 2022. Based on the outcomes of the clinical examination, laboratory tests, coronary angiography (COA), acute myocardial infarction (MI) type ST-elevation myocardial infarction (STEMI), stable angina pectoris (SAP), and healthy control groups were tested. Each sample was subjected to Sanger sequencing. The polymorphism was significantly linked to stable angina and myocardial infarction Genotype CC was higher in SAP when compared with MI and control groups which was statistically significant with (p-value<0.05). A higher proportion of C allele was observed in SAP patients (15.7%) which was significantly higher than MI (14.58%) and control (10.8%). The statistical chi-square analysis for allele G frequency showed insignificant differences (p-value>0.05) between patients and the control group. Genetic variation in E-selectin such as polymorphism in nucleotide 7170 G>C at exon 4 region can significantly affect the outcome of cardiovascular diseases.

Circulating secretoneurin level reflects angiographic coronary collateralization in stable angina patients with chronic total occlusion.

OBJECTIVE: To investigate the association between circulating secretoneurin (SN) and angiographic coronary collateralization in stable angina patients with chronic coronary total occlusion (CTO). METHODS: SN concentrations in serum were measured in 641 stable angina patients with CTO by radioimmunoassay. The status of coronary collaterals from the contra-lateral vessel was visually estimated using the Rentrop grading system, and was categorized into poor (grade 0 or 1) or good (grade 2 or 3) collateralization. RESULTS: Serum SN levels were significantly higher in patients with good coronary collaterals compared to those with poor collaterals (175.23 ± 52.09 pmol/L vs. 143.29 ± 42.01 pmol/L, P < 0.001). Serum SN increased stepwise across Rentrop score 0 to 3 (P < 0.001), and increasing SN tertiles were associated with higher proportion of good coronary collateralization (OR, 1.907; 95% CI, 1.558 ~ 2.335, P < 0.001). After adjustment for confounding variables, serum SN (per tertile) remained an independent factor for predicting good coronary collaterals (OR, 1.870; 95% CI, 1.515 ~ 2.309; P < 0.001). Moreover, the diagnostic value of serum SN (per tertile) was consistent after stratifying patients based on gender, age, body mass index, hypertension, diabetes, history of smoking, severity of coronary artery disease and kidney function (OR: 1.511 ~ 2.680, P interaction ≥ 0.327). CONCLUSION: Elevated circulating SN reflects good angiographic coronary collaterals in stable angina patients with CTO. The findings may provide insight into decision-making for these patients.

Transcription factor 21 rs12190287 polymorphism is related to stable angina and ST elevation myocardial infarction in a Chinese Population.

Background: Transcription factor 21 (TCF21, epicardin, capsuling, pod-1) is expressed in the epicardium and is involved in the regulation of cell fate and differentiation via epithelial-mesenchymal transformation during development of the heart. In addition, TCF21 can suppress the differentiation of epicardial cells into vascular smooth muscle cells and promote cardiac fibroblast development. This study aimed to explore whether TCF21 gene (12190287G/C) variants affect coronary artery disease risk. Methods: We enrolled 381 patients who had stable angina, 138 with ST elevation myocardial infarction (STEMI), and 276 healthy subjects. Genotyping of rs12190287 of the TCF21 gene was performed. Results: Higher frequencies of the CC genotype were found in the patients with stable angina/STEMI than in the healthy controls. After adjusting for diabetes mellitus, hypertension, age, sex, smoking, body mass index and hyperlipidemia, the patients with the CC genotype of the TCF21 gene were associated with 2.49- and 9.19-fold increased risks of stable angina and STEMI, respectively, compared to the patients with the GG genotype. Furthermore, TCF21 CC genotypes showed positive correlations with both stable angina and STEMI, whereas TCF21 GG genotypes exhibited a negative correlation with STEMI. Moreover, the stable angina and STEMI patients with the CC genotype had significantly elevated high-sensitivity C-reactive protein levels than those with the GG genotype. In addition, significant associations were found between type 2 diabetes mellitus, hypertension, and hyperlipidemia with TCF21 gene polymorphisms (p for trend < 0.05). Conclusion: TCF21 gene polymorphisms may increase susceptibility to stable angina and STEMI.

Atrial fibrillation incidence after coronary artery bypass graft surgery and percutaneous coronary intervention: the prospective AFAF cohort study.

Objectives. Atrial fibrillation is a common arrhythmia in patients with ischemic heart disease. This study aimed to determine the cumulative incidence of new-onset atrial fibrillation after percutaneous coronary intervention or coronary artery bypass grafting surgery during 30 days of follow-up. Design. This was a prospective multi-center cohort study on atrial fibrillation incidence following percutaneous coronary intervention or coronary artery bypass grafting for stable angina or non-ST-elevation acute coronary syndrome. Heart rhythm was monitored for 30 days postoperatively by in-hospital telemetry and handheld thumb ECG recordings after discharge were performed. The primary endpoint was the cumulative incidence of atrial fibrillation 30 days after the index procedure. Results. In-hospital atrial fibrillation occurred in 60/123 (49%) coronary artery bypass graft and 0/123 percutaneous coronary intervention patients (p < .001). The cumulative incidence of atrial fibrillation after 30 days was 56% (69/123) of patients undergoing coronary artery bypass grafting and 2% (3/123) of patients undergoing percutaneous coronary intervention (p < .001). CABG was a strong predictor for atrial fibrillation compared to PCI (OR 80.2, 95% CI 18.1-354.9, p < .001). Thromboembolic stroke occurred in-hospital in one coronary artery bypass graft patient unrelated to atrial fibrillation, and at 30 days in two additional patients, one in each group. There was no mortality. Conclusion. New-onset atrial fibrillation during 30 days of follow-up was rare after percutaneous coronary intervention but common after coronary artery bypass grafting. A prolonged uninterrupted heart rhythm monitoring strategy identified additional patients in both groups with new-onset atrial fibrillation after discharge.

The impact of statins treatments for plaque characteristics in stable angina pectoris patients with very low and high low-density lipoprotein cholesterol levels: an intracoronary optical coherence tomography study.

Low-density lipoprotein cholesterol (LDL-C) levels are recommended according to the patient's risk factors based on guidelines. In patients achieving low LDL-C levels, the need for statins is uncertain, and the plaque characteristics of patients not treated with statins are unclear. In addition, the difference in plaque characteristics with and without statins is unclear in similarly high LDL levels. We evaluate the impact of statins on plaque characteristics on optical coherence tomography (OCT) in patients with very low LDL-C levels and high LDL-C levels. A total of 173 stable angina pectoris patients with 173 lesions undergoing OCT before percutaneous coronary intervention were evaluated. We divided the LDL-C levels into three groups: < 70 mg/dL (n = 48), 70 mg/dL ≤ LDL-C < 100 mg/dL (n = 71), and ≥ 100 mg/dL (n = 54). Among patients with LDL-C < 70 mg/dL, patients not treated with statins showed a significantly higher C-reactive protein level (0.27 ± 0.22 mg/dL vs. 0.15 ± 0.19 mg/dL, p = 0.049), and higher incidence of thin-cap fibroatheromas (TCFAs; 44% [7/16] vs. 13% [4/32], p = 0.021) than those treated with statins. Among patients with LDL-C level ≥ 100 mg/dL, patients treated with statins showed a significantly higher prevalence of familial hypercholesterolemia (FH) (38% [6/16] vs. 5% [2/38], p = 0.004), lower incidence of TCFAs (6% [1/16] vs. 39% [15/38], p = 0.013), healed plaques (13% [2/16] vs. 47% [18/38], p = 0.015), and higher incidence of fibrous plaques (75% [12/16] vs. 42% [16/38], p = 0.027) than patients not treated with statins. While patients achieved a low LDL-C, patients not treated with statins had high plaque vulnerability and high systemic inflammation. While patients had a high LDL-C level with a high prevalence of FH, patients treated with statins had stable plaque characteristics.

Effects of Remote Ischaemic Conditioning in Stable and Unstable Angina Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.

AIM: Type 4a myocardial infarction (T4aMI), defined as myocardial injury associated with percutaneous coronary intervention (PCI), is associated with a poor prognosis and there is conflicting evidence regarding the effectiveness of remote ischaemic conditioning (RIC) in its prevention. This review aimed to determine the effect of RIC on stable and unstable angina patients. METHOD: A systematic review was conducted in PubMed and Central database. Outcome measures were: changes in peak troponin, creatine kinase myocardial band (CKMB), C-reactive protein (CRP) level, incidence of T4aMI, and major adverse cardiovascular event (MACE). Data were meta-analysed and reported as standardised mean difference (SMD) and odds ratio (OR). Risk of bias was assessed with the Risk of Bias 2 (RoB2) tool. RESULTS: Fifteen studies with no significant risk of bias were included. Peak troponin level was reduced in the RIC group, particularly after excluding a study with low statin use, while CKMB and CRP levels resulted in a non-significant SMD between the groups. The incidence of T4aMI was significantly lower in the intervention group (OR 0.714; p=0.026); this finding was also seen in subgroups of elective PCI, pre-conditioning, and high statin use. Incidence of MACE also only reached statistically significant protective effects with OR <1 in similar subgroups. No substantial heterogeneity was found and the funnel plot did not show publication bias. CONCLUSION: Remote ischaemic conditioning in elective PCI patients has been proven to be potentially beneficial in reducing peak troponin levels and risk of T4aMI and MACE.

Study on the Therapeutic Value of Shexiang Tongxin Dropping Pills in Patients with Stable Angina Pectoris of Coronary Heart Disease Complicated with Cognitive Impairment.

BACKGROUND: There is a pressing need to identify pharmaceuticals that are both safe and efficacious, with lower toxicity, for the treatment of stable angina pectoris in individuals suffering from coronary heart disease. The aim of this paper is to explore the therapeutic value of Shexiang Tongxin Dropping Pills in patients with stable angina pectoris of coronary heart disease complicated with cognitive impairment. METHODS: 200 patients with stable angina pectoris combined with cognitive dysfunction and coronary heart disease admitted to our hospital from January 2022 to June 2023 were retrospectively selected as the study objects. According to the treatment method, the subjects were divided into a control group and a study group, with 100 cases in each group. The control group received conventional oral Western medicine, and the study group underwent treatment with Shexiang Tongxin Dropping Pills in addition to traditional Western medicine. The course of treatment was eight weeks. The enhancement in angina pectoris, cognitive function level, self-care ability, and clinical efficacy of both groups were assessed by comparing the conditions before and after the treatment. RESULTS: After treatment, the frequency and duration of angina pectoris attacks in both groups were significantly lower than before, and the study group was lower than the control group (p < 0.05). The Montreal Cognitive Assessment (MoCA) score of both groups was higher than before, and the score of the study group was significantly higher than that of the control group (p < 0.05). Neuropsychiatric Inventory (NPI) scores in both groups were significantly lower than before, and the scores of the study group were significantly lower than those of the control group (p < 0.05). Traditional Chinese Medicine (TCM) syndrome scores in both groups were significantly lower than before, and the scores of the study group were significantly lower than those of the control group (p < 0.05). After treatment, the total effective rate of the control group and the study group was 81.00% and 93.00%, respectively, and the total clinical effective rate of the study group was significantly higher than that of the control group (p < 0.05). CONCLUSION: Shexiang Tongxin Dropping Pills can effectively reduce the incidence of angina pectoris in patients with stable angina pectoris complicated with coronary heart disease and cognitive dysfunction. It can also regulate the patient's neurological function, improve their cognitive level, and significantly improve clinical efficacy.

Prognostic Value of Coronary CT Angiography-derived Fractional Flow Reserve on 3-year Outcomes in Patients with Stable Angina.

Background The prognostic value of coronary CT angiography (CTA)-derived fractional flow reserve (FFR) beyond 1-year outcomes and in patients with high levels of coronary artery calcium (CAC) is uncertain. Purpose To assess the prognostic value of coronary CTA-derived FFR test results on 3-year clinical outcomes in patients with coronary stenosis and among a subgroup of patients with high levels of CAC. Materials and Methods This study represents a 3-year follow-up of patients with new-onset stable angina pectoris who were consecutively enrolled in the Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care, known as ADVANCE (ClinicalTrials.gov: NCT02499679) registry, between December 2015 and October 2017 at three Danish sites. A high CAC was defined as an Agatston score of at least 400. A lesion-specific coronary CTA-derived FFR value of 2 cm with distal-to-stenosis value at or below 0.80 represented an abnormal test result. The primary end point was a composite of all-cause death and nonfatal spontaneous myocardial infarction. Event rates were estimated using the one-sample binomial model, and relative risk was compared between participants stratified by results of coronary CTA-derived FFR. Results This study included 900 participants: 523 participants with normal results (mean age, 64 years ± 9.6 [SD]; 318 male participants) and 377 with abnormal results from coronary CTA-derived FFR (mean age, 65 years ± 9.6; 264 male participants). The primary end point occurred in 11 of 523 (2.1%) and 25 of 377 (6.6%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 3.1; 95% CI: 1.6, 6.3; P < .001). In participants with high CAC, the primary end point occurred in four of 182 (2.2%) and 19 of 212 (9.0%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 4.1; 95% CI: 1.4, 11.8; P = .001). Conclusion In individuals with stable angina, a normal coronary CTA-derived FFR test result identified participants with a low 3-year risk of all-cause death or nonfatal spontaneous myocardial infarction, both in the overall cohort and in participants with high CAC scores. Clinical trial registration no. NCT02499679 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Sinitsyn in this issue.

Chronic remote ischemic conditioning treatment in patients with chronic stable angina (EARLY-MYO-CSA): a randomized, controlled proof-of-concept trial.

BACKGROUND: Chronic remote ischemic conditioning (CRIC) has been shown to improve myocardial ischemia in experimental animal studies; however, its effectiveness in patients with chronic stable angina (CSA) has not been investigated. We conducted a proof-of-concept study to investigate the efficacy and safety of a six-month CRIC treatment in patients with CSA. METHODS: The EARLY-MYO-CSA trial was a prospective, randomized, controlled trial evaluating the CRIC treatment in patients with CSA with persistent angina pectoris despite receiving ≥ 3-month guideline-recommended optimal medical therapy. The CRIC and control groups received CRIC (at 200 mmHg) or sham CRIC (at 60 mmHg) intervention for 6 months, respectively. The primary endpoint was the 6-month change of myocardial flow reserve (MFR) on single-photon emission computed tomography. The secondary endpoints were changes in rest and stress myocardial blood flow (MBF), angina severity according to the Canadian Cardiovascular Society (CCS) classification, the Seattle Angina Questionnaire (SAQ), and a 6-min walk test (6-MWT). RESULTS: Among 220 randomized CSA patients, 208 (105 in the CRIC group, and 103 in the control group) completed the treatment and endpoint assessments. The mean change in MFR was significantly greater in the CRIC group than in the control group (0.27 ± 0.38 vs. - 0.04 ± 0.25; P < 0.001). MFR increased from 1.33 ± 0.48 at baseline to 1.61 ± 0.53 (P < 0.001) in the CRIC group; however, a similar increase was not seen in the control group (1.35 ± 0.45 at baseline and 1.31 ± 0.44 at follow-up, P = 0.757). CRIC treatment, when compared with controls, demonstrated improvements in angina symptoms assessed by CCS classification (60.0% vs. 14.6%, P < 0.001), all SAQ dimensions scores (P < 0.001), and 6-MWT distances (440 [400-523] vs. 420 [330-475] m, P = 0.016). The incidence of major adverse cardiovascular events was similar between the groups. CONCLUSIONS: CSA patients benefit from 6-month CRIC treatment with improvements in MFR, angina symptoms, and exercise performance. This treatment is well-tolerated and can be recommended for symptom relief in this clinical population. TRIAL REGISTRATION: [chictr.org.cn], identifier [ChiCTR2000038649].

An elevated triglyceride-glucose index predicts adverse outcomes and interacts with the treatment strategy in patients with three-vessel disease.

BACKGROUND: Insulin resistance is a pivotal risk factor for cardiovascular diseases, and the triglyceride-glucose (TyG) index is a well-established surrogate of insulin resistance. This study aimed to investigate the prognostic value of the TyG index and its ability in therapy guidance in patients with three-vessel disease (TVD). METHODS: A total of 8862 patients with TVD with available baseline TyG index data were included in the study. The endpoint was major adverse cardiac events (MACE). All patients received coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy (MT) alone reasonably. RESULTS: An elevated TyG index was defined as the TyG index greater than 9.51. During a median follow-up of 7.5 years, an elevated TyG index was significantly associated with an increased risk of MACE (adjusted hazard ratio 1.161, 95% confidence interval 1.026-1.314, p = 0.018). The elevated TyG index was shown to have a more pronounced predictive value for MACE in patients with diabetes, but failed to predict MACE among those without diabetes, whether they presented with stable angina pectoris (SAP) or acute coronary syndrome (ACS). Meanwhile, the association between an elevated TyG index and MACE was also found in patients with left main involvement. Notably, CABG conferred a significant survival advantage over PCI in patients with a normal TyG index, but was not observed to be superior to PCI in patients with an elevated TyG index unless the patients had both ACS and diabetes. In addition, the benefit was shown to be similar between MT and revascularisation among patients with SAP and an elevated TyG index. CONCLUSIONS: The TyG index is a potential indicator for risk stratification and therapeutic decision-making in patients with TVD.

Coronary arterial repair in patients with stable angina pectoris or acute coronary syndrome after ultrathin biodegradable polymer sirolimus-eluting stent implantation at 1-year follow-up by coronary angioscopy.

BACKGROUND: Imaging modality-based evidence is limited that compares the extent of coronary arterial repair after percutaneous coronary intervention between patients with stable angina pectoris (SAP) and those with acute coronary syndrome (ACS). METHODS: Between December 2018 and November 2021, a single-center, nonrandomized, observational study was conducted in 92 patients with SAP (n = 42) or ACS (n = 50), who were implanted with Orsiro sirolimus-eluting stent (O-SES) providing a hybrid (active and passive) coating and underwent 1-year follow-up by coronary angioscopy (CAS) after implantation. CAS assessed neointimal coverage (NIC), maximum yellow plaque (YP), and mural thrombus (MT). RESULTS: Baseline clinical characteristics were comparable between the SAP and ACS groups. The follow-up periods were comparable between the two groups (390.1 ± 69.9 vs. 390.6 ± 65.7 days, p = 0.99). The incidences of MT at 1 year after implantation were comparable between the two groups (11.4% vs. 11.1%, p = 0.92). The proportions of "Grade 1" in dominant NIC grades were highest in both groups, and the proportions of maximum YP grades and MT were comparable between the two groups. CONCLUSION: O-SES-induced coronary arterial repair at the site of stent implantation, irrespective of the types of coronary artery disease.

Proteomic Characterization of Atherosclerotic Lesions In Situ Using Percutaneous Coronary Intervention Angioplasty Balloons-Brief Report.

BACKGROUND: Materials extracted from atherosclerotic arteries can disclose data about the molecular pathology of cardiovascular disease, but obtaining such samples is complex and requires invasive surgery. To overcome this barrier, this study investigated whether angioplasty balloons inflated during standard percutaneous coronary interventions retain proteins from treated (dilated) atherosclerotic lesions and whether proteomic analysis of this material could provide data on lesion protein profiles and distinguish between patients with stable and unstable coronary artery disease. METHODS: Patients with ST-segment-elevation myocardial infarction and stable angina pectoris were subjected to routine percutaneous coronary interventions. All angioplasty balloons inflated in a coronary artery were collected. Proteins retained on the balloons were extracted and analyzed using shotgun proteomic analysis. RESULTS: Proteomics identified and quantified 1365 unique proteins captured on percutaneous coronary intervention balloons. Control balloons inflated in the ascending aorta showed minimal nonspecific protein binding, indicating specificity to the luminal region of atherosclerotic lesions of the diseased artery wall. Clustering and principal component analyses showed that ST-segment-elevation myocardial infarction and stable angina pectoris subjects could be separated by variations in protein content and abundance. We identified 206 proteins as differentially abundant between ST-segment-elevation myocardial infarction and stable angina pectoris subjects. Pathway analysis indicated several enriched processes in the ST-segment-elevation myocardial infarction group involved in neutrophil-mediated immunity and platelet activation. CONCLUSIONS: Disease-related proteins from coronary artery lesions adhere to angioplasty balloons and constitute a source of material for proteomic analysis. This approach can identify proteins and processes occurring in unstable coronary atherosclerotic lesions and suggest novel therapeutic approaches.

Clinical Significance of Coronary Healed Plaques in Stable Angina Pectoris Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Coronary healed plaques (HPs) reportedly have high vulnerability or show advanced atherosclerosis and a risk of rapid plaque progression. However, the prognosis of stable angina pectoris (SAP) patients with HPs undergoing percutaneous coronary intervention (PCI) remains under-investigated.Methods and Results: We analyzed 417 consecutive lesions from SAP patients undergoing pre- and post-intervention optical coherence tomography (OCT) for which HPs were defined as having a layered appearance. We investigated the differences in clinical and lesion characteristics, and post-PCI outcomes between HPs and non-HPs. To account for differences in clinical characteristics, propensity score matching was performed between the groups. HPs were observed in 216 lesions (51.8%) in the total cohort. In the propensity-matched cohort (n=294), HPs had higher rates of angiographic-B2/C lesions (77.6% vs. 59.2%, P<0.001), OCT-lipid-rich plaques (40.8% vs. 25.9%, P=0.007), macrophages (78.2% vs. 44.2%, P<0.001), greater luminal area stenosis (73.5±11.0% vs. 71.5±10.3%, P=0.002), and a higher prevalence of post-stenting irregular tissue protrusion (45.1% vs. 14.7%, P<0.001) than non-HPs. In the total cohort, target lesion revascularization (TLR)-free survival was poorer for HPs (log-rank test 7.66; P=0.006), and Cox proportional hazards analysis showed HP as an independent predictor of TLR (hazard ratio, 5.98; 95% confidence interval, 1.72-20.82; P=0.005). CONCLUSIONS: In SAP patients, HPs had greater complexity of lesions and higher vulnerability, which may have contributed to the poorer post-PCI outcomes.

Evaluating hs-cTnI serum levels and cTnI gene expression compared with cardiac nuclear scan in patients with angina pectoris.

Exercise stress can cause reversible myocardial ischemia in people with coronary artery disease (CAD). On the other hand, the new troponin biomarker with high sensitivity can detect faster and small amounts of troponin in blood circulation. The present study aimed to investigate the serum troponin level following exercise stress and the result of nuclear heart scans as the gold standard. For this purpose, 93 patients with stable angina and no history of known CAD and organic disease were included in this cross-sectional study. The serum level of the highly sensitive cardiac troponin I (hs-cTnI) was measured 75 minutes after the peak of the exercise test and reached at least 85% of the maximum heart rate. It was compared with the rate of reversible myocardial ischemia based on the nuclear heart scan, the three-month prognosis and the persistence of chest pain were investigated. Also, the expression level of the cTnI gene was evaluated by real-time PCR technique. The results showed that the average age of the patients was 58.9+12.4 years, and 62 (66.66%) patients were female. Reversible myocardial ischemia was observed in 31 patients. The relationship between hs-cTI level and the rate of reversible ischemia cases was significant (p = 0.0041). Also, the cTnI gene expression showed the same results as the serum level. According to the heart nuclear scan report, the hs-cTnI value above 1.6ng/dl had a specificity of 72% and sensitivity of 66%, a positive predictive value of 53%, and a negative predictive value of 78%. There was no significant relationship between hs-cTnI level and prognosis and the continuation of chest pain in patients after three months. Generally, the serum level of high-sensitivity cardiac troponin was higher after exercise in the group with reversible myocardial ischemia.