The Efficacy of Coronary Sinus Reducer in Patients with Refractory Angina: A Systematic Review and Meta-Analysis.

Background: Refractory angina is a frequently encountered phenomenon in patients with coronary artery disease, often presenting therapeutic challenges to the clinical cardiologist. Novel treatment methods have been explored in this direction, with the coronary sinus reducer (CSR) being among the most extensively-investigated. Methods: We conducted a systematic review of the literature for studies assessing the efficacy of CSR in patients with refractory angina. The primary endpoints of interest were procedural success and the improvement in angina according to the Canadian Cardiovascular Society (CCS) by at least one class. Secondary endpoints were the rate of periprocedural adverse events, the improvement by at least 2 CCS classes, and the mean change in CCS class. A random-effects meta-analysis of proportions (procedural success, improvement by ≥ 1 or ≥ 2 classes, periprocedural adverse events) or means (mean CCS class change) were performed. I 2 was chosen as the metric for between-study heterogeneity. Publication bias was assessed by the inspection of funnel plots and Egger's regression test. We examined the risk of bias according to the Newcastle-Ottawa Scale. Results: From a total of 515 studies identified from the original search, 12 studies were finally included for data extraction. Based on their meta-analysis, we observed a high CSR procedural success (98%, 95% confidence interval (CI) 96 to 99%) with a low rate of periprocedural complications (6%, 95% CI 5 to 7%), while most patients exhibited an improvement by at least 1 CCS class (75%, 95% CI 66 to 83%) after the intervention. A significant proportion of patients demonstrated an improvement by at least 2 CCS classes (39%, 95% CI 34 to 45%), with a mean change of -1.24 CCS class (95% CI -1.40 to -1.08). Conclusions: CSR is associated with high implantation success rates and significant improvements in angina symptoms for patients with refractory angina.

The Impact of Coronary Sinus Reducer on Arrhythmic Properties in Patients with Refractory Angina.

Background: Treatment with a coronary sinus reducer (CSR) is a new therapeutic option for refractory angina patients. Preclinical studies have shown antiarrhythmic properties of coronary sinus narrowing. The possible antiarrhythmic effect of CSR implantation is unknown. This study aimed to determine the possible antiarrhythmic effects of CSR implantation as assessed by high-resolution electrocardiogram (hrECG) parameters. Methods: 24 patients from the Crossroad study randomized to either CSR treatment (n = 12) or a sham procedure (n = 12) had hrECG recorded at baseline and after 6 months. T-peak and T-end interval (TpTe) defined as the time difference between the peak amplitude of the T wave and the global end of the T wave, spatial angle between QRS complex and T axis defined as the angle between the ventricular depolarization and repolarization vectors using maximal (QRSTP) and mean (QRSTM) vector amplitudes and spatial ventricular gradient (SVG) calculated as integral of ECG voltages over the entire QRST complex were analyzed. Additionally, we analyzed parameters of QT and heart rate variability using time and frequency domain. Results: At baseline, all analyzed parameters were comparable between both groups and heart rate remained constant. The intragroup analysis did not show any significant change in TpTe, QRSTP, QRSTM, SVG, QT, and heart rate variability at follow-up. Furthermore, intergroup comparison between CSR implantation and sham procedure also did not show any significant difference in the change of analyzed parameters. Conclusions: Compared to the sham procedure, CSR implantation did not demonstrate a significant impact on the arrhythmogenic substrate assessed with hrECG. Clinical Trial Registration: Unique Identifier: NCT04121845, https://classic.clinicaltrials.gov/ct2/show/NCT04121845.

Keeping it in the family: Use of the grandmother, mother, and child technique to navigate complex anatomy during Coronary sinus Reducer Implantation.

The Coronary Sinus Reducer® (CSR) is an emerging therapy for refractory angina recommended once no further pharmacologic or coronary revascularization options are available. We present the case of a 72-year-old man who underwent CSR implantation. Complex coronary sinus anatomy necessitated an innovative "grandmother, mother, and child" catheter approach.

Beneficial effects of atrial fibrillation ablation in patients with angina pectoris and coronary sinus reducer.

Limited data exists about the effectiveness of the coronary sinus reducer (CSR) device in patients with angina pectoris and atrial fibrillation (AF). This case demonstrates beneficial effects of AF ablation in a patient with CSR. We report four major findings: Rhythm control has a relevant effect on angina pectoris symptoms in patients with coronary artery disease and AF. In these patients, AF ablation should be considered at an early stage. Patients with persistent angina pectoris and CSR may require sinus rhythm for an optimal effect of the device. Selected coronary sinus (CS) interventions can still be performed through the mesh of the CSR device.

Efficacy of coronary sinus Reducer in patients with refractory angina and diabetes mellitus.

Coronary sinus Reducer (CSR) implantation is currently recommended to relieve angina in patients with refractory symptoms despite optimal medical therapy and maximally achievable revascularization. The impact of diabetes mellitus on outcome after CSR implantation is at present unknown. We aimed to explore the impact of CSR in refractory angina patients with diabetes mellitus. Data from consecutive patients undergoing CSR implantation at four different centres between 2014 and 2018 were included. Patients were divided according to the presence or absence of diabetes mellitus. Primary objective of this analysis was to evaluate the clinical response to CSR implantation defined as an improvement of ≥ 1 classes of the Canadian Cardiovascular Society (CCS) Classification. A total of 219 patients were included, 116 (53%) of whom had diabetes mellitus. The median age of the population was 69 years and 167 patients (76%) were male. There were no significant differences between groups of patients with and without diabetes mellitus with respect to CCS class at baseline (p value = 0.32) and at follow-up (p = 0.75). Over a median follow-up of 393 [224-1004] days, 84 (72%) of the patients with diabetes mellitus met the primary outcome, similarly to those without diabetes mellitus (p = 0.28). Fifty-three patients (24%) did not have an improvement in CCS class and no one experienced worsening of angina. CSR implantation was equally effective in improving angina symptoms among patients with refractory angina and diabetes mellitus compared to patients without diabetes mellitus.

Coronary sinus size and ischemia improvement after reducer implantation; "one size to fit them all?"

AIM: Coronary sinus (CS) reducer implantation is associated with symptomatic relief of patients with refractory angina. However, 15% to 30% of the patients do not respond to this treatment. Aim if this study was to evaluate the effect of CS size in the effectiveness of the device. METHODS: Prior to device implantation and at 4-month resting ventricular function was assessed by stress cardiac magnetic resonance. Ischemia was assessed by the myocardial perfusion reserve index (MPRI). RESULTS: Fifteen patients (66 ± 10 years) underwent successful CS Reducer implantation, with improvements in angina class and exercise tolerance. Patients with a smaller CS size (<5.8 mm) presented a significantly higher percentage increase in MPRI (63 ± 51 vs 9 ± 30%, P = .03) and a higher reduction in left ventricle end-diastolic volumes. CONCLUSIONS: Greater benefits, in terms of ischemia improvement, after CS Reducer implantation were seen in patients with smaller CS sizes, suggesting a potential mechanism underlying the observed rates of reducer non-responsiveness.

Coronary sinus anatomical features: Description and procedural implications during coronary sinus Reducer implantation.

OBJECTIVES: We hypothesized that some coronary sinus (CS) anatomies allow a more straightforward CS Reducer (CSR) implantation. BACKGROUND: Recent decades have seen a rise in patients with chronic angina. When complete revascularization and maximal medical therapy fail to reduce symptoms, CSR has become a new therapeutic option. METHODS: We identified a classical C-shape-a near horizontal course of the proximal portion of a circular CS-in a retrospective analysis of 47 CSR implantations and compared the procedural time, fluoroscopic time, contrast use, presence of valves or bifurcations and procedural complications with the non-C-shape CS anatomy. RESULTS: We found a significant difference in procedural (20.0 [19.0-24.7] min vs. 24.5 [20.7-51.0] min; p = .028 and fluoroscopic time (9.5 [7.5-14.5] min vs. 11.0 [7.9-30.0] min; p = .016). There was no significant difference in contrast use. The presence of bifurcations or valves along the CS course did not influence the procedural timings. CONCLUSION: This study is the first systematic evaluation of CS anatomy and its procedural implications. We identified a favorable C-shape anatomy which allows for a more straightforward implantation. Operators should be aware of the different implications of CS anatomy, their influence on guiding catheter stability and overall procedure complexity.

Coronary Sinus Reducer for the Treatment of Chronic Refractory Angina: Will This Challenge the Treatment of Coronary Chronic Total Occlusions?

PURPOSE OF REVIEW: The prevalence of angina despite optimal medical therapy is high among patients with coronary chronic total occlusions. Despite advancements in techniques and operator's experience, percutaneous revascularization of coronary chronic total occlusions is still associated with a not negligible risk of failures and complications. The Coronary Sinus Reducer, a new device developed to improve angina, has shown promising results in terms of efficacy and safety in patients with refractory symptoms. The aim of this review is to summarize the evidence so far available and to guide clinicians in the selection of patients with chronic total occlusions that could benefit more from Coronary Sinus Reducer implantation. RECENT FINDINGS: A recently published study suggests a clear value of this device in patients with chronic total occlusions. This is likely to be related to the presence of a well-developed collateral circulation. A careful evaluation of risks and benefits of both myocardial revascularization and Coronary Sinus Reducer implantation should be done in all the cases in order to better define the optimal strategy for the patient. The Coronary Sinus Reducer implantation has a rationale in patients with chronic total occlusion as an alternative or additional therapy to myocardial revascularization.

The Coronary Sinus Reducer; 5-year Dutch experience.

BACKGROUND: Refractory angina is a growing and major health-care problem affecting millions of patients with coronary artery disease worldwide. The Coronary Sinus Reducer (CSR) is a device that may be considered for the relief of symptoms of refractory angina. It causes increased venous pressure leading to a dilatation of arterioles and reduced arterial vascular resistance in the sub-endocardium. This study describes the 5­year Dutch experience regarding safety and efficacy of the CSR. METHODS: One hundred and thirty-two patients with refractory angina were treated with the CSR. The primary efficacy endpoint of the study was Canadian Cardiovascular Society (CCS) class improvement between baseline and 6­month follow-up. The primary safety endpoint was successful CSR implantation in the absence of any device-related events. RESULTS: Eighty-five patients (67%) showed improvement of at least 1 CCS class and 43 patients (34%) of at least 2 classes. Mean CCS class improved from 3.17 ± 0.61 to 2.12 ± 1.07 after implantation (P < 0.001). The CSR was successfully implanted in 99% of the patients and only minor complications during implantation were reported. CONCLUSION: The CSR is a simple, safe, and effective option for most patients with refractory angina. However, approximately thirty percent of the patients showed no benefit after implantation. Future studies should focus on the exact underlying mechanisms of action and reasons for non-response to better identify patients that could benefit most from this therapy.

The impact of the coronary sinus reducer upon left ventricular function in patients with refractory angina pectoris.

OBJECTIVES: To evaluate the impact of coronary sinus (CS) Reducer implantation upon left ventricular (LV) function. BACKGROUND: CS Reducer implantation is associated with symptomatic relief in patients with refractory angina. The effects of the device upon left ventricular function remains unknown. METHODS: Prior to device implantation and at 4-months, resting ventricular volumes and function were measured using cardiac magnetic resonance (CMR). Stress CMR was performed to extract quantitative indices of myocardial perfusion (myocardial perfusion reserve index-MPRI). RESULTS: Nineteen patients (18 males, 66.0 [IQR 56.0-77.0] years), underwent successful Reducer implantation. Sixteen (84%) patients improved by at least 1 CCS class. Four months after Reducer implantation, we noticed a significant improvement in LV ejection fraction (LVEF) (61 [IQR 47-71] to 66 [IQR 57-72] %; p = .009), a reduction in LV end-diastolic volume (LVEDV)/Body surface area (BSA) (65.7 [IQR 57.4-89.6] to 64.7 [IQR 53.7-74.1] mL/m2 ; p = .036) and a reduction in LV end-systolic volume (LVESV)/BSA (28.7 [IQR 18.6-38.8] to 20.0 [IQR 15.0-31.4] mL/m2 ; p = .007). Patients with reduced EF (EF < 50%, n = 6) presented a greater increase of EF at follow up compared to patients with preserved EF (11.3 [IQR 6.5-54.5] vs. 3.8 [IQR 0.6-9.1] %; p = .029). The observed decrease in LVESV/BSA was greater in patients with reduced EF (23.6 [IQR 11.6-33.8] vs. 4.2 [IQR -2.0 to 8.4] mL/m2 ; p = .005). A significant increase in transmural MPRI was observed 4 months after Reducer implantation (p < .011). CONCLUSIONS: CS Reducer improved angina symptoms and improved left ventricular function. The improvement was pronounced in the subgroup of patients with reduced ejection fraction. Myocardial perfusion improvement could represent the underlying mechanism for the observed benefits.

Implantation of a Coronary Sinus Reducer to Treat Refractory Angina in a 38-Year-Old with an Anomalous Left Coronary Artery and No Revascularization Options.

A 38-year-old female with anomalous left coronary artery from the pulmonary artery presented with refractory angina (Canadian Cardiovascular Society [CCS] class 4). Having failed two previous internal mammary artery grafts to the left anterior descending artery and with no percutaneous revascularization options, she underwent coronary sinus reducer implantation, which improved her symptoms (CCS 0), quality of life, and corresponded to an improvement in ischemia on myocardial perfusion scanning. This case report describes an unusual case of refractory angina in the context of congenital heart disease, illustrates the benefit of this novel hourglass-shaped stent in improving ischemia, quality of life, depression and anxiety, and highlights the importance of managing these patients in multidisciplinary teams.

Angina and left ventricular dysfunction: can we 'reduce' it?

Despite the evolution in pharmacology and devices, recurrent and persistent angina still represent a frequent issue in clinical practice. A 69-year-old Caucasian female patient has history of surgical aortic valve replacement with a bioprosthesis for severe aortic stenosis with subsequent transcatheter valve-in-valve implantation for bioprosthesis degeneration and single coronary artery bypass graft with left internal mammary artery on left anterior descending (LAD). After transcatheter aortic valve implantation, she started to complain angina [Canadian Cardiovascular Society (CCS) Class III], effectively treated with bisoprolol uptitration and ivabradine 5 b.i.d. addition. After 6 months, she had a non-ST segment elevated myocardial infarction with evidence of left main occlusion and good functioning aortic bioprosthesis. A retrograde drug-eluting balloon percutaneous coronary intervention (PCI) on LAD (in-stent restenosis) was performed. However, the patient continued to complain angina (CCS Class II-III), even after further ivabradine increase to 7.5 mg b.i.d. After 4 months, the patient underwent Reducer implantation. After 2 months, angina started to improve and the patient is currently angina free. In the last decades, PCI materials and stents greatly improved. Medical therapy (such as ß-blockers) has been shown not only to improve symptoms but also to add a prognostic benefit in patients with reduced ejection fraction (EF). Ivabradine showed additional benefits in patients with angina and reduced EF. However, still a relevant portion of patients complain refractory angina. The COSIRA trial showed that a coronary sinus Reducer was associated with greater angina relief than the sham procedure and could be a further step in angina treatment.

The efficacy of coronary sinus reducer in patients with refractory angina-A systematic review of the literature.

OBJECTIVES: The aim of our systematic review was to investigate the efficacy of coronary sinus (CS) reducer device in patients with refractory angina. BACKGROUND: The CS reducer device provides a therapeutic option for patients with coronary artery disease who are not suitable for revascularization. METHODS: Two independent investigators (GB and GT) systematically searched the Medline and Cochrane library databases for studies describing the efficacy and safety of the CS reducer in patients with refractory angina from January 1, 2000 until May 12, 2018 using the following terms: "coronary sinus (reducer OR reducing) device." Efficacy was defined as ≥1 unit improvement in the Canadian cardiovascular society (CCS) score. RESULTS: Our search strategy provided six studies (five observational studies and one randomized clinical trial) with 196 patients. The CS reducer device was effective in 146/186 (78.5%) patients. CCS score improved from 3.2 at baseline to 1.9 after 8.6 months of follow-up. The efficacy of CS reducer device was also demonstrated as an improvement in Seattle Angina Questionnaire score, dobutamine echocardiography, thalium single-photon emission computed tomography perfusion studies, 6-min-walk test and myocardial perfusion reserve index. Implantation failed in 4 of 196 (2%) patients and 5 patients (2.5%) had a complication during 30-day follow-up. CONCLUSIONS: The CS reducer is a promising treatment option for patients with refractory angina who are not candidates for revascularization. However, larger randomized control trials with long-term follow-up are needed to elucidate its role.

Coronary Sinus Stent: Could It Help in Refractory Chronic Stable Angina?

Refractory angina is a life-disabling disease, even with the discovery of antianginal drugs and the advances in revascularization surgically or percutaneously to improve symptoms. Over the last decade a renewal of interest in an old surgical modality of narrowing the coronary sinus has evolved. Although the surgical procedure idea was born in 1940 it was overshadowed by the development of coronary artery bypass graft and percutaneous interventions. Recently, a percutaneous approach of reducing the coronary sinus size has been developed and several clinical studies have been reported in refractory angina patients. We review the history of coronary sinus intervention, and explore coronary sinus stent possible mechanism of action, device design, and the clinical data supporting its use.

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.

Coronary Sinus Reducer Therapy for Refractory Angina and its Role in Modern Interventional Practice: A Contemporary Review.

Coronary sinus reducer (CSR) implantation is an emerging treatment option for patients with refractory angina. This condition represents a major global cardiovascular healthcare challenge, with patients experiencing chronic anginal symptoms that significantly impair their quality of life and for whom few effective treatments exist. The clinical burden of refractory angina is only set to grow because of improved survival from coronary artery disease, increased life expectancy and the presence of residual angina after percutaneous or surgical coronary revascularisation. Therefore, new, effective, evidence-based therapies are urgently needed. In this review, we highlight the unmet clinical needs of patients with refractory angina, discuss the development of the CSR device and review the preclinical and clinical evidence base underlying CSR implantation. In addition, we discuss the current role of CSR implantation in contemporary interventional practice, highlighting knowledge gaps and discussing areas of on-going research.

[Coronary sinus reducer : Technical aspects, prevention and management of potential complications]. / Réducteur de sinus coronaire : aspects techniques, prévention et gestion des complications.

Coronary sinus reducer implantation is a percutaneous technique creating a narrowing in the coronary sinus through the implantation of an hourglass-shaped endoprosthesis. It is proposed to reduce symptoms in patients suffering from refractory angina pectoris. This innovative treatment is experiencing a major craze among interventional cardiologists. It is associated with very high procedural success rates. Complications are rare and include coronary sinus dissection or perforation and migration of the device. This review exposes the device implantation technique, the potential anatomical difficulties, the tips and tricks to overcome challenging situations. It also focuses on the prevention and management of potential complications.

Safety and Effectiveness of Coronary Sinus Reducer in the Therapy of Refractory Angina Pectoris-Mid-Term Results of the Real-Life Cohort.

Background: Despite continuous improvements in revascularization techniques, refractory angina without potential revascularization options remains a relevant clinical issue with significant impact on the patient's quality of life. Recently, a novel device, the Coronary Sinus Reducer (CSR), has been introduced into clinical practice as a therapeutic option for patients with disabling angina pectoris. In this single-center, observational study, we evaluated the mid-term (3-month) safety and efficacy of the CSR in a real-world cohort. Methods: The study population consisted of 55 patients with refractory angina without potential revascularization options, who were predominantly men (87.3%) with a high cardiovascular risk factor burden and advanced angina (baseline CCS angina class 3.15 ± 0.6). In terms of procedure safety, all patients underwent successful device deployment with only one periprocedural complication. Results: At the 3-month follow-up, we observed a statistically significant improvement in angina control measured CCS class and SAQ-7 total questionnaire along with increased abolition of physical limitation-6-MWT (233.3 ± 107.1 vs. 305.2 ± 126.8; p < 0.0001). Additionally, we observed significant improvement in terms of quality of life measurements SF-36, the EQ-5D-5L questionnaire, and the EQ-VAS. Conclusions: Our real-world data suggest that CSR implantation is a relatively safe procedure and appears to be particularly effective in relieving angina symptoms and improving quality of life in subjects with refractory angina.

Coronary sinus narrowing therapy: A "Reducer" for angina and beyond.

Refractory Angina (RA) is an increasingly common clinical diagnosis, in which patients unsuitable for further percutaneous or surgical procedures experience anginal symptoms, despite receiving optimal medical therapy. This clinical condition challenges the everyday activities and diminishes the quality of life of these patients. A wide variety of novel therapies for this type of angina are being investigated for clinical use. One of them is coronary sinus narrowing, which is performed as a percutaneous interventional procedure using catheter-delivered device, the Reducer. The device is implanted in the coronary sinus creating a physical narrowing and a pressure gradient in the sinus. This intervention improves the impaired blood flow in the ischemic regions of the heart leading to the relief of the anginal symptoms and, therefore, the overall clinical improvement of these patients. Several clinical trials have established both the safety and efficacy of the coronary sinus Reducer, while ongoing trials are aiming to further establish the procedure's safety and efficiency in both RA and other cardiovascular diseases, such as coronary microvascular dysfunction. This review aims to discuss the pathophysiology and the role of the coronary sinus Reducer in RA, the clinical trials documenting its safety and efficacy, as well as the future perspectives of this procedure among cardiovascular diseases.