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.

Pressure-Controlled Intermittent Coronary Sinus Occlusion (PiCSO) in Acute Myocardial Infarction: The PiCSO-AMI-I Trial.

BACKGROUND: Primary percutaneous coronary intervention (pPCI) has improved clinical outcomes in patients with ST-segment-elevation myocardial infarction. However, as many as 50% of patients still have suboptimal myocardial reperfusion and experience extensive myocardial necrosis. The PiCSO-AMI-I trial (Pressure-Controlled Intermittent Coronary Sinus Occlusion-Acute Myocardial Infarction-I) evaluated whether PiCSO therapy can further reduce myocardial infarct size (IS) in patients undergoing pPCI. METHODS: Patients with anterior ST-segment-elevation myocardial infarction and Thrombolysis in Myocardial Infarction flow 0-1 were randomized at 16 European centers to PiCSO-assisted pPCI or conventional pPCI. The PiCSO Impulse Catheter (8Fr balloon-tipped catheter) was inserted via femoral venous access after antegrade flow restoration of the culprit vessel and before proceeding with stenting. The primary end point was the difference in IS (expressed as a percentage of left ventricular mass) at 5 days by cardiac magnetic resonance. Secondary end points were the extent of microvascular obstruction and intramyocardial hemorrhage at 5 days and IS at 6 months. RESULTS: Among 145 randomized patients, 72 received PiCSO-assisted pPCI and 73 conventional pPCI. No differences were observed in IS at 5 days (27.2%±12.4% versus 28.3%±11.45%; P=0.59) and 6 months (19.2%±10.1% versus 18.8%±7.7%; P=0.83), nor were differences between PiCSO-treated and control patients noted in terms of the occurrence of microvascular obstruction (67.2% versus 64.6%; P=0.85) or intramyocardial hemorrhage (55.7% versus 60%; P=0.72). The study was prematurely discontinued by the sponsor with no further clinical follow-up beyond 6 months. However, up to 6 months of PiCSO use appeared safe with no device-related adverse events. CONCLUSIONS: In this prematurely discontinued randomized trial, PiCSO therapy as an adjunct to pPCI did not reduce IS when compared with conventional pPCI in patients with anterior ST-segment-elevation myocardial infarction. PiCSO use was associated with increased procedural time and contrast but no increase in adverse events up to 6 months. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03625869.

A rare case of isolated persistent left superior vena cava diagnosed by echocardiography.

BACKGROUND: The persistent left superior vena cava (PLSVC) is an infrequent vascular variant. PLSVC with absent right superior vena cava, also known as isolated PLSVC, is an exceptionally rare entity. In this case we present a patient with isolated PLSVC draining to coronary sinus, diagnosed incidentally during echocardiography. CASE PRESENTATION: A 35-year-old man underwent a transthoracic echocardiography which showed an enormously dilated coronary sinus. Hand-agitated saline was injected via peripheral intravenous cannulas. The contrast appeared firstly in the coronary sinus before it opacified the right atrium. Since this was also visible by the right antecubital saline injection, it indicated an extremely rare case of PLSVC with the absence of right superior vena cava which was confirmed by cardiac magnetic resonance. CONCLUSIONS: The finding of a distinctively dilated coronary sinus in echocardiography led us to further investigation using agitated saline that revealed an infrequent anomaly termed isolated PLSVC. The in-depth diagnosis of this vascular variant is crucial considering that it may lead to important clinical implications, such as difficulties with central venous access, especially in the current era of a rapid development of cardiac device therapies.

Surgical management of multiple coronary artery to coronary sinus fistulas with giant left circumflex artery and multivalvular infective endocarditis.

Coronary artery fistula (CAF) is characterized as a congenital or acquired abnormal communication between a coronary artery and any of the four chambers of the heart (coronary-cameral fistula) or great vessels (coronary arteriovenous fistula) bypassing the capillaries within myocardium. CAF is a rare disease, challenging to diagnose and treat depending on the anatomical location and type of the fistula and accompanying diseases. This study aims to report a case with multiple coronary artery to coronary sinus (CS) fistulas with giant left circumflex artery and multivalvular infective endocarditis.

Giant coronary sinus aneurysm: an incidental discovery in a case of acute coronary syndrome.

Coronary sinus (CS) anomalies, although infrequent, are increasingly diagnosed with advances in interventional procedures and imaging techniques. Most cases are asymptomatic and incidentally diagnosed. We present a case of an elderly male without comorbidities who presented with acute angina. Coronary catheterisation revealed a double-vessel disease, but incidentally, sequential angiograms captured contrast filling in the levophase of CS, revealing a giant CS. Primary percutaneous angioplasty of the right coronary artery was performed successfully. Echocardiography confirmed the aneurysm, and a CT scan showed an aneurysmally dilated CS and other coronary veins alongside a normal-sized persistent left superior vena cava draining to the right atrium through CS. CS aneurysms may lead to complications such as thrombosis, embolic events, arrhythmias and heart failure, stressing the importance of vigilant monitoring and timely intervention. This case underscores the significance of recognising CS anomalies in cardiac procedures, even when asymptomatic, for proper management.

Snare technique failure in extracting an embolized coronary sinus reducer to the pulmonary artery.

We report the case of a 79-year-old male patient who benefited from the implantation of a coronary sinus reducer (CSR) (Reducer; Neovasc, Inc.) in the management of typical angina with mild exertion with optimal medical treatment.

Mechanisms of coronary sinus reducer for treatment of myocardial ischemia: in silico study.

The coronary sinus reducer (CSR) is an emerging medical device for treating patients with refractory angina, often associated with myocardial ischemia. Patients implanted with CSR have shown positive outcomes, but the underlying mechanisms are unclear. This study sought to understand the mechanisms of CSR by investigating its effects on coronary microcirculation hemodynamics that may help explain the therapy's efficacy. We applied a validated computer model of the coronary microcirculation to investigate how CSR affects hemodynamics under different degrees of coronary artery stenosis. With moderate coronary stenosis, an increase in capillary transit time (CTT) [up to 69% with near-complete coronary sinus (CS) occlusion] is the key change associated with CSR. Because capillaries in the microcirculation can still receive oxygenated blood from the upstream artery with moderate stenosis, the increase in CTT allows more time for the exchange of gases and nutrients, aiding tissue oxygenation. With severe coronary stenosis; however, the redistribution of blood draining from the nonischemic region to the ischemic region (up to 96% with near-complete CS occlusion) and the reduction in capillary flow heterogeneity are the key changes associated with CSR. Because blood draining from the nonischemic region is not completely devoid of O2, the redistribution of blood to the capillaries in the ischemic region by CSR is beneficial especially when little or no oxygenated blood reaches these capillaries. This simulation study provides insights into the mechanisms of CSR in improving clinical symptoms. The mechanisms differ with the severity of the upstream stenosis.NEW & NOTEWORTHY Emerging coronary venous retroperfusion treatments, particularly coronary sinus reducer (CSR) for refractory angina linked to myocardial ischemia, show promise; however, their mechanisms of action are not well understood. We find that CSR's effectiveness varies with the severity of coronary stenosis. In moderate stenosis, CSR improves tissue oxygenation by increasing capillary transit time, whereas in severe stenosis, it redistributes blood from nonischemic to ischemic regions and reduces capillary flow heterogeneity.

Left coronary sinus of valsalva aneurysm dissecting into interventricular septum: a case report.

BACKGROUND: Sinus of Valsalva aneurysm (SVA) is an extremely rare condition, and its rupture causes acute symptoms such as chest pain and dyspnea. Ruptured SVA is frequently associated with other congenital defects. CASE PRESENTATION: A 37-year-old male presented with SVA originating from the left coronary sinus that ruptured into the interventricular septum. SVA was diagnosed by echocardiography, cardiac computed tomography and magnetic resonance imaging, and confirmed during the operation. CONCLUSIONS: SVA is a rare cardiac abnormality which can lead to severe clinical symptoms upon rupture. Immediate surgery is necessary to repair the ruptured SVA.

Anatomical Study of the Cardiac Veins and their Tributaries in Bovines (Bos indicus) in Comparison with Humans and Other Animal Species / Estudio Anatómico de las Venas Cardiacas y sus Tributarias en Bovinos (Bos indicus) en Comparación con Humanos y Otras Especies Animales

SUMMARY: In bovines, anatomical observations of the coronary vascular tree describe qualitative characteristics. The objective of this study was to morphometrically characterize the coronary veins and their tributaries in cattle. An arcuate application with 2.0 silk was performed around the ostium of the coronary sinus of 28 bovine hearts and a number 14 catheter was placed, through which semi- synthetic polyester resin and mineral blue color was perfused. In 22 hearts (78.6 %) the great cardiac vein was originated at the cardiac apex. The configuration of the arteriovenous trigone was mainly closed inferior and superior types (50 %). The caliber of the great cardiac vein at the level of the atrioventricular sulcus was 6.7 +/- 1.2 mm. The origin of the left marginal vein was observed in the lower third of the left cardiac margin (53.6 %), its distal caliber was 4.1 +/- 0.8 mm and its drainage was at the level of the great cardiac vein. The middle cardiac vein originated from the cardiac apex in 78.6 % of the samples, emptied mainly into the coronary sinus (82.1 %) and its distal caliber was 4.7 +/- 0.9 mm. Anastomoses occurred in 28.6 % of the hearts, being found in most cases between the middle cardiac vein and the great cardiac vein (50 %), which was significant compared to other anastomoses (p<0.001). The length of the coronary sinus was 42.2 +/- 5.1 mm, its distal caliber was 13.8 +/- 2 mm, and its shape was cylindrical. Myocardial bridges were found in 3 hearts (10.7 %) mainly in the lower third of the middle cardiac vein (66.6 %). Most of the main coronary veins drained into the coronary sinus, with some cases with atypical outlets and the presence of a high percentage of anastomosis that serves to improve cardiac venous drainage in case of venous compression or obstruction.

En bovinos, las observaciones anatómicas de árbol vascular coronario describen características cualitativas. El objetivo de este estudio fue caracterizar morfométricamente las venas coronarias y sus tributarias en bovinos. Se realizó una aplicatura arciforme con seda 2.0 alrededor del ostium del seno coronario de 28 corazones de bovino y se colocó un catéter número 14, a través del cual se perfundió resina de poliéster semisintética y color azul mineral. La vena cardiaca magna se originó en 22 corazones (78,6 %) en el ápex cardiaco. La configuración del trígono arteriovenoso fue principalmente cerrado inferior y superior (50 %). El calibre de la vena cardiaca magna a nivel del surco atrioventricular fue 6,7 +/- 1,2 mm. El origen de la vena marginal izquierda se observó en el tercio inferior del margen izquierdo cardiaco (53,6 %), su calibre distal fue 4,1 +/- 0,8 mm y su desembocadura fue a nivel de la vena cardiaca magna. La vena cardiaca media se originó en el ápex cardiaco en el 78,6 % de las muestras, desembocó principalmente en el seno coronario (82.1 %) y su calibre distal fue 4,7 +/- 0,9 mm. Se presentó anastomosis en el 28,6 % de los corazones, encontrándose en la mayoría de los casos entre la vena cardiaca media y la vena cardiaca magna (50 %), lo cual fue significativo en comparación con otras anastomosis (p<0,001). La longitud del seno coronario fue 42,2 +/- 5,1 mm, su calibre distal fue 13,8 +/- 2 mm y su forma fue cilíndrica. Se encontró puentes miocárdicos en 3 corazones (10,7 %) y en el tercio inferior de la vena cardiaca media (66,6 %). La mayoría de las venas coronarias principales desembocan en el seno coronario, con algunos casos con desembocaduras atípicas y la presencia de un alto porcentaje de anastomosis que sirve para mejorar el drenaje venoso cardiaco en caso de compresión u obstrucción venosa.

Coronary Sinus Narrowing Improves Coronary Microcirculation Function in Patients With Refractory Angina: A Multicenter Prospective INROAD Study.

BACKGROUND: The underlying mechanisms responsible for the clinical benefits following coronary sinus narrowing and pressure elevation remain unclear. The present study aims to investigate whether coronary sinus narrowing improves the indexes of coronary microcirculatory function. METHODS: Patients with refractory angina who had a clinical indication for reducer implantation underwent invasive physiological assessments before and 4 months after the procedure. The primary outcome was the change in the values of the index of microcirculatory resistance. Secondary end points included changes in coronary flow reserve and the resistive resistance ratio values. Angina status was assessed with the Canadian Cardiology Society class and the Seattle Angina Questionnaire. RESULTS: Twenty-four patients with a history of obstructive coronary artery disease and prior coronary revascularization (surgical and percutaneous) treated with reducer implantation were enrolled, and 21 of them (87%) underwent repeated invasive coronary physiological assessment after 4 months. The index of microcirculatory resistance values decreased from 33.35±19.88 at baseline to 15.42±11.36 at 4-month follow-up (P<0.001; mean difference, -17.90 [95% CI, -26.16 to -9.64]). A significant (≥20% from baseline) reduction of the index of microcirculatory resistance was observed in 15 (71.4% [95% CI, 47.8%-88.7%]) patients. The number of patients with abnormal index of microcirculatory resistance (≥25) decreased from 12 (57%) to 4 (19%; P=0.016). Coronary flow reserve increased from 2.46±1.52 to 4.20±2.52 (mean difference, 1.73 [95% CI, 0.51-2.96]). Similar findings were observed for resistive resistance ratio values. Overall, 16 patients (76.1%) had an improvement of 1 Canadian Cardiology Society class. Seattle Angina Questionnaire summary score increase of around 3 points (3.01 [95% CI, 1.39-4.61]). CONCLUSIONS: Coronary sinus reduction implantation is associated with a significant improvement in the parameters of coronary microcirculatory function. These findings provide insights into the improvement of angina symptoms and may have implications for the treatment of coronary microvascular dysfunction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05174572.

A double-blind, randomised, placebo-controlled trial of the coronary sinus Reducer in refractory angina: design and rationale of the ORBITA-COSMIC trial.

The coronary sinus Reducer (CSR) is an hourglass-shaped device which creates an artificial stenosis in the coronary sinus. Whilst placebo-controlled data show an improvement in angina, these results are unreplicated and are the subject of further confirmatory research. The mechanism of action of this unintuitive therapy is unknown. The Coronary Sinus Reducer Objective Impact on Symptoms, MRI Ischaemia, and Microvascular Resistance (ORBITA-COSMIC) trial is a randomised, placebo-controlled, double-blind trial investigating the efficacy of the CSR. Patients with (i) established epicardial coronary artery disease, (ii) angina on maximally tolerated antianginal medication, (iii) evidence of myocardial ischaemia and (iv) no further options for percutaneous coronary intervention or coronary artery bypass grafting will be enrolled. Upon enrolment, angina and quality-of-life questionnaires, treadmill exercise testing and quantitative stress perfusion cardiac magnetic resonance (CMR) imaging will be performed. Participants will record their symptoms daily on a smartphone application throughout the trial. After a 2-week symptom assessment phase, participants will be randomised in the cardiac catheterisation laboratory to CSR or a placebo procedure. After 6 months of blinded follow-up, all prerandomisation tests will be repeated. A prespecified subgroup will undergo invasive coronary physiology assessment at prerandomisation and follow-up. The primary outcome is stress myocardial blood flow on CMR. Secondary outcomes include angina frequency, quality of life and treadmill exercise time. (ClinicalTrials.gov: NCT04892537).

The effect of an initial catheter ablation with an adjunctive ethanol infusion into the vein of Marshall on persistent atrial fibrillation.

INTRODUCTION: Some previous studies have reported that a first-step ethanol infusion into the vein of Marshall (EIVOM) with touch-up radiofrequency (RF) ablation can facilitate mitral isthmus (MI) block and improves the ablation outcomes in persistent atrial fibrillation (PeAF) patients. However, the effect of an initial RF ablation with an adjunctive EIVOM has not been fully investigated. METHODS: This study enrolled 233 PeAF patients undergoing pulmonary vein isolation and linear ablation including an MI, roof line, and cavotricuspid isthmus ablation. An EIVOM was performed when endocardial ablation with or without coronary sinus ablation failed to create MI block. RESULTS: Bidirectional MI block was achieved in 224 patients (96.1%). Among them, MI block was obtained by only RF ablation in 174/224 patients (77.7%) (RF group) and an adjunctive EIVOM was needed in 50/224 (22.3%) (EIVOM group). During the follow-up, 113 (64.9%) RF group patients were free from AF/atrial tachycardia compared to 41 (82.0%) EIVOM group patients (log-rank p = .045). In a multivariate Cox regression analysis, an adjunctive EIVOM was associated with a lower recurrence rate (hazard ratio = 0.39, 95% confidence interval = 0.17-0.78, p = .006). CONCLUSION: An initial RF ablation with an adjunctive EIVOM strategy improved MI ablation's acute success rate and was associated with better clinical outcomes.