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.

Distinct Challenges of Eruptive and Non-Eruptive Calcified Nodules in Percutaneous Coronary Intervention.

PURPOSE OF REVIEW: To provide a summary of prevalence, pathogenesis, and treatment of coronary calcified nodules (CNs). RECENT FINDINGS: CNs are most frequently detected at the sites of hinge motion of severely calcified lesions such as in the middle segment of right coronary artery and left main coronary bifurcation. On histopathology, CNs exhibit two distinctive morphologies: eruptive and non-eruptive. Eruptive CNs, which have a disrupted fibrous cap with adherent thrombi, are biologically active. Non-eruptive CNs, which have an intact fibrous cap without thrombi, are biologically inactive, representing either healed eruptive CNs or protrusion of calcium due to plaque progression. Recent studies using optical coherence tomography (OCT) have shown a difference in the mechanism of stent failure in the two subtypes, demonstrating early reappearance of eruptive CNs in the stent (at ~ 6 months) as a unique mechanism of stent failure that does not seem to be preventable by simply achieving adequate stent expansion. The cause of CN reappearance in stent is not known and could be due to acute or subacute intrusion or continued growth of the CN. Whether modification of CN is needed, the most effective calcium modification modality and effectiveness of stent implantation in eruptive CNs has not been elucidated. In this review, we discuss pathogenesis of CNs and how intravascular imaging can help diagnose and manage patients with CNs. We also discuss medical and transcatheter therapies beyond conventional stent implantation for effective treatment of eruptive CNs that warrant testing in prospective studies.

Percutaneous Coronary Intervention of Native Artery Versus Bypass Graft in Patients with Prior Coronary Artery Bypass Graft Surgery.

Background: Percutaneous coronary intervention (PCI) is common in patients with prior coronary artery bypass graft surgery (CABG), however, there is limited data on the association between the PCI target-vessel and clinical outcomes. In this article, we provide a state-of-the-art overview of the contemporary management of patients with prior CABG and a clear indication for revascularization. Methods: We performed a structured literature search of PubMed and Cochrane Library databases from inception to March 2021. Relevant studies were extracted and synthesized for narrative review. Results: Twenty-six observational studies focusing on PCI of bypass graft versus native coronary artery lesions in 366,060 patients with prior CABG were included. The data from observational studies suggest that bypass graft PCI is associated with higher short- and long-term major adverse cardiac events compared to native coronary artery PCI. Conclusions: Whenever feasible, native coronary artery PCI should be the prioritized treatment for saphenous vein graft failure. Prospective randomized trials are needed to elucidate the optimal revascularization strategy for patients with prior CABG.

Unintended Deformation of Stents During Bifurcation PCI: An OCTOBER Trial Substudy.

BACKGROUND: Unintended deformation of implanted coronary stents can lead to loss of coronary access, stent thrombosis and coronary events during follow-up. The incidence, mechanisms and clinical outcomes of unintended stent deformations (USD) during complex bifurcation stenting are not well characterized. OBJECTIVES: In a prespecified analysis of the OCTOBER (European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction) trial, we aimed to: 1) determine the incidence and characterize mechanisms of USD identified by optical coherence tomography (OCT); and 2) evaluate physician's detection and correction of accidental abluminal rewiring and USD. METHODS: OCT scans were analyzed for accidental abluminal rewiring and USD. When USD was identified, the plausible mechanism was determined by analysis of all procedural OCT scans and the corresponding angiograms. RESULTS: USD was identified by the core lab in 9.3% (55/589) of OCT-guided cases. Accidental abluminal rewiring was the cause in 44% (24/55), and guide catheter collision was the cause in 40% (22/55) of cases. USD was found in 18.5% of all cases with left main bifurcation percutaneous coronary intervention. The total incidence of abluminal rewiring was 33 in 32 OCT-guided cases (5.4%) and was corrected by physicians in 18 of 33 appearances (54.5%). The 2-year major adverse cardiac event rate for patients with untreated USD (n = 30) was 23.3%, whereas patients with confirmed or possibly corrected USD (n = 25) had no events during follow-up. CONCLUSIONS: USD was associated with adverse procedural complications and cardiac events during follow-up when not identified and corrected. The predominant mechanisms were undetected abluminal rewiring and guide catheter collision. Left main bifurcation percutaneous coronary intervention was a particular risk with USD detected in 18.5% of cases.

Calcified Nodule in Percutaneous Coronary Intervention: Therapeutic Challenges.

Calcified nodules (CNs) are among the most challenging lesions to treat in contemporary percutaneous coronary intervention. CNs may be divided into 2 subtypes, eruptive and noneruptive, which have distinct histopathological and prognostic features. An eruptive CN is a biologically active lesion with a disrupted fibrous cap and possibly adherent thrombus, whereas a noneruptive CN has an intact fibrous cap and no adherent thrombus. The use of intravascular imaging may allow differentiation between the 2 subtypes, thus potentially guiding treatment strategy. Compared with noneruptive CNs, eruptive CNs are more likely to be deformable, resulting in better stent expansion, but are paradoxically associated with worse clinical outcomes, in part because of their frequent initial presentation as an acute coronary syndrome and subsequent reprotrusion of the CN into the vessel lumen through the stent struts. Pending the results of ongoing studies, a tailored therapeutic approach based on the distinct features of the different CNs may be of value.

Safety and Effectiveness of a Novel Microcatheter in Coronary Chronic Total Occlusions-The BIOMICS Study.

Background: Chronic total occlusion (CTO) remains the most complex anatomical subset of lesions in percutaneous coronary intervention (PCI), often requiring advanced techniques and technologies, including the use of microcatheters. Methods: The BIOMICS study is a premarket first-in-human prospective, multicenter, open-label, single-arm trial investigating the safety and efficacy of a novel coronary microcatheter (BioMC, Biosensors International) in 100 patients with symptoms of ischemia undergoing elective CTO-PCI. The primary efficacy end point of the study was device success defined according to the CTO-ARC (Chronic Total Occlusion Academic Research Consortium) criteria namely the ability of the microcatheter to successfully facilitate placement of a guide wire beyond the occluded coronary segment. The primary safety end point was the incidence of in-hospital cardiac death or myocardial infarction at hospital discharge. Results: Hundred patients were recruited between March 2022 and January 2023. The primary efficacy end point was achieved in 75% of patients (95% CI, 65.3%-83.1%; P < .0001 for superiority compared to the prespecified performance goal of 54%). The primary safety end point of in-hospital cardiac death or myocardial infarction was observed in 2% of the patients. There were no study device-related coronary perforations or device failures. Conclusions: The use of a novel coronary microcatheter during CTO-PCI was associated with a high device success and an excellent safety profile.

Impact of Anatomical and Viability-Guided Completeness of Revascularization on Clinical Outcomes in Ischemic Cardiomyopathy.

BACKGROUND: Complete revascularization of coronary artery disease has been linked to improved outcomes in patients with preserved left ventricular (LV) function. OBJECTIVES: This study sought to identify the impact of complete revascularization in patients with severe LV dysfunction. METHODS: Patients enrolled in the REVIVED-BCIS2 (Revascularization for Ischemic Ventricular Dysfunction) trial were eligible if baseline/procedural angiograms and viability studies were available for analysis by independent core laboratories. Anatomical and viability-guided completeness of revascularization were measured by the coronary and myocardial revascularization indices (RIcoro and RImyo), respectively, where RIcoro = (change in British Cardiovascular Intervention Society Jeopardy score [BCIS-JS]) / (baseline BCIS-JS) and RImyo= (number of revascularized viable segments) / (number of viable segments supplied by diseased vessels). The percutaneous coronary intervention (PCI) group was classified as having complete or incomplete revascularization by median RIcoro and RImyo. The primary outcome was death or hospitalization for heart failure. RESULTS: Of 700 randomized patients, 670 were included. The baseline BCIS-JS and SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores were 8 (Q1-Q3: 6-10) and 22 (Q1-Q3: 15-29), respectively. In those patients assigned to PCI, median RIcoro and RImyo values were 67% and 85%, respectively. Compared with the group assigned to optimal medical therapy alone, there was no difference in the likelihood of the primary outcome in those patients receiving complete anatomical or viability-guided revascularization (HR: 0.90; 95% CI: 0.62-1.32; and HR: 0.95; 95% CI: 0.66-1.35, respectively). A sensitivity analysis by residual SYNTAX score showed no association with outcome. CONCLUSIONS: In patients with severe LV dysfunction, neither complete anatomical nor viability-guided revascularization was associated with improved event-free survival compared with incomplete revascularization or treatment with medical therapy alone. (Revascularization for Ischemic Ventricular Dysfunction) [REVIVED-BCIS2]; NCT01920048).

Advanced CT Imaging for the Assessment of Calcific Coronary Artery Disease and PCI Planning.

Vascular calcification is a hallmark of atherosclerosis and adds considerable challenges for percutaneous coronary intervention (PCI). This review underscores the critical role of coronary computed tomography (CT) angiography in assessing and quantifying vascular calcification for optimal PCI planning. Severe calcification significantly impacts procedural outcomes, necessitating accurate preprocedural evaluation. We describe the potential of coronary CT for calcium assessment and how CT may enhance precision in device selection and procedural strategy. These advancements, along with the ongoing Precise Procedural and PCI Plan study, represent a transformative shift toward personalized PCI interventions, ultimately improving patient outcomes in the challenging landscape of calcified coronary lesions.

SYNERGY-Everolimus-Eluting Stent With a Bioabsorbable Polymer in ST-Elevation Myocardial Infarction: CLEAR SYNERGY OASIS-9 Registry.

Our objective was to evaluate the clinical effectiveness of the SYNERGY stent (Boston Scientific Corporation, Marlborough, Massachusetts) in patients with ST-elevation myocardial infarction (STEMI). The only drug-eluting stent approved for treatment of STEMI by the Food and Drug Administration is the Taxus stent (Boston Scientific) which is no longer commercially available, so further data are needed. The CLEAR (Colchicine and spironolactone in patients with myocardial infarction) SYNERGY stent registry was embedded into a larger randomized trial of patients with STEMI (n = 7,000), comparing colchicine versus placebo and spironolactone versus placebo. The primary outcome for the SYNERGY stent registry is major adverse cardiac events (MACE) as defined by cardiovascular death, recurrent MI, or unplanned ischemia-driven target vessel revascularization within 12 months. We estimated a MACE rate of 6.3% at 12 months after primary percutaneous coronary intervention for STEMI based on the Thrombectomy vs percutaneous coronary intervention alone in STEMI (TOTAL) trial. Success was defined as upper bound of confidence interval (CI) to be less than the performance goal of 9.45%. Overall, 733 patients were enrolled from 8 countries with a mean age 60 years, 19.4% diabetes mellitus, 41.3% anterior MI, and median door-to-balloon time of 72 minutes. The MACE rate was 4.8% (95% CI 3.2 to 6.3%) at 12 months which met the success criteria against performance goal of 9.45%. The rates of cardiovascular death, recurrent MI, or target vessel revascularization were 2.7%, 1.9%, 1.0%, respectively. The rates of acute definite stent thrombosis were 0.3%, subacute 0.4%, late 0.4%, and cumulative stent thrombosis of 1.1% at 12 months. In conclusion, the SYNERGY stent in STEMI performed well and was successful compared with the performance goal based on previous trials.

Symptoms as a Predictor of the Placebo-Controlled Efficacy of PCI in Stable Coronary Artery Disease.

BACKGROUND: Placebo-controlled evidence from ORBITA-2 (Objective Randomised Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina-2) found that percutaneous coronary intervention (PCI) in stable coronary artery disease with little or no antianginal medication relieved angina, but residual symptoms persisted in many patients. The reason for this was unclear. OBJECTIVES: This ORBITA-2 secondary analysis investigates the relationship between presenting symptoms and disease severity (anatomic, noninvasive, and invasive ischemia) and the ability of symptoms to predict the placebo-controlled efficacy of PCI. METHODS: Prerandomization symptom severity and nature were assessed using the ORBITA smartphone application and symptom and quality of life questionnaires including the World Health Organization Rose angina questionnaire (Rose). Disease severity was assessed using quantitative coronary angiography, stress echocardiography, fractional flow reserve, and instantaneous wave-free ratio. Bayesian ordinal regression was used. RESULTS: At prerandomization, the median number of daily angina episodes was 0.8 (Q1-Q3: 0.4-1.6), 64% had Rose angina, quantitative coronary angiography diameter stenosis was 61% (Q1-Q3: 49%-74%), stress echocardiography score was 1.0 (Q1-Q3: 0.0-2.7), fractional flow reserve was 0.63 (Q1-Q3: 0.49-0.75), and instantaneous wave-free ratio was 0.78 (Q1-Q3: 0.55-0.87). There was little relationship between symptom severity and nature and disease severity: angina symptom score with quantitative coronary angiography ordinal correlation coefficient: 0.06 (95% credible interval [CrI]: 0.00-0.08); stress echocardiography: 0.09 (95% CrI: 0.02-0.10); fractional flow reserve: 0.04 (95% CrI: -0.03 to 0.07); and instantaneous wave-free ratio: 0.04 (95% CrI: -0.01 to 0.07). However, Rose angina and guideline-based typical angina were strong predictors of placebo-controlled PCI efficacy (angina symptom score: OR: 1.9; 95% CrI: 1.6-2.1; probability of interaction [PrInteraction] = 99.9%; and OR: 1.8; 95% CrI: 1.6-2.1; PrInteraction = 99.9%, respectively). CONCLUSIONS: Although symptom severity and nature were poorly associated with disease severity, the nature of symptoms powerfully predicted the placebo-controlled efficacy of PCI.