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.

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.

A Case of Refractory Variant Angina.

Coronary vasospasm is defined as the abnormal contraction of an epicardial coronary artery. Variant angina is a severe form of coronary vasospasm, reflecting transmural ischemia with ST-T elevation on an electrocardiogram. A pharmacologic spasm provocation test during coronary angiography is the gold standard evaluation for patients who have not been diagnosed with coronary vasospasm by a non-invasive test. The sensitivity and specificity of pharmacologic spasm provocation testing have been reported to be very high in patients with variant angina. Here, we report the case of a 61-year-old woman who had refractory variant angina. Although a pharmacologic spasm provocation test did not lead to a definitive diagnosis, she had recurrent acute coronary syndrome due to coronary vasospasm. Physicians should be aware of the limitations of the spasm provocation test, even in patients with refractory variant angina.

A budget impact model and a cost-utility analysis of reducer device (Neovasc) in patients with refractory angina.

Background: Refractory angina (RA) is a chronic condition characterized by the presence of debilitating angina symptoms due to established reversible ischemia in the presence of obstructive coronary artery disease (CAD). Treatments for this condition have undergone major developments in recent decades; however, the treatment for RA remains a challenge for medicine. In this sense, the Coronary Sinus Reducer System (CSRS) stands as the last line of therapy for ineligible patients for revascularization with reversible ischemia. The purpose of this report is to evaluate the potential burden on the National Health Service (NHS) and measure the health effects in terms of both quantity (life years) and quality-of-life aspects related to the reducer. Methods: Two different economic evaluation models were developed as part of the analysis. The budget impact was developed to estimate the potential burden on the NHS from incremental uptake of the use of the reducer in the target population. The utility cost analysis compares and evaluates the quality of life and health resource use and costs between the two alternatives, based on the research of Gallone et al. A deterministic and probabilistic sensitivity analysis was carried out to characterize the uncertainty around the parameters of the model. Results: In the budget impact analysis (BIA), the reducer is shown to be more expensive in the first 2 years of the model, due to the gradual uptake in the market and the cost of the device. Starting from the third year, assuming maintenance of effectiveness, there are savings in terms of resource absorption in direct healthcare costs arising from hospitalizations, emergency department accesses, coronarography, and visits avoided. Conclusion: The BIA and cost-effectiveness model show that the reducer device, despite an increase in resources absorbed in the first years of implementation and use, has the potential to result in increased quality of life in patients with RA. These costs are largely offset in the short term by the improved clinical outcomes achievable leading to savings from the third year onward in the BIA and a dominance ratio in the cost-utility analysis.

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.

Ischemic Myocardial Positron Emission Tomography Perfusion Without Epicardial Coronary Disease in Hypertrophic Obstructive Cardiomyopathy.

The presence of impaired microvascular coronary flow (MCF) identified by positron emission tomography myocardial perfusion imaging (PET-MPI) has been described in hypertrophic obstructive cardiomyopathy (HOCM) patients, contributes to blunted myocardial perfusion during vasodilator stress, and is a strong predictor of poor prognosis. A 45-year-old female with hypertension and obesity presented with angina. Her PET-MPI displayed vasodilator stress-induced global LV ischemia. However, her coronary angiogram revealed no obstructive coronary disease. These contradictory findings triggered a more thorough cardiac MRI with diffuse myocardial fibrosis, indicating high-risk HOCM. She underwent implantable cardioverter-defibrillator (ICD) placement due to non-sustained ventricular tachycardia and syncope. While this patient lacked epicardial coronary disease, her PET-MPI demonstrated global LV ischemia due to decreased MCF, leading to inadequate augmentation of myocardial perfusion during hyperemia. This is a well-described phenomenon responsible for anginal symptoms in HOCM patients. HOCM hearts have abnormally thick coronary arterioles and decreased capillary density, leading to increased oxygen diffusion distances and reduced perfusion. The presence of vasodilator-induced, global ischemia on PET-MPI without epicardial stenosis should raise suspicion for HOCM with impaired MCF, which represents a high-risk population with an almost 10 times greater risk of cardiovascular mortality compared to hypertrophic cardiomyopathy with preserved MCF.

Proangiogenic Growth Factor Therapy for the Treatment of Refractory Angina: A Meta-analysis.

Background: Refractory angina (RFA; limiting angina despite optimal medical therapy) is a growing, global problem, with limited treatment options. Therefore, we conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effect of proangiogenic growth factor therapy (in the form of vascular growth factors delivered either as recombinant proteins or gene therapy) in patients with RFA ineligible for revascularization. Methods: We performed a meta-analysis (PROSPERO: CRD42018107283) of RCTs as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. A comprehensive search of the PubMed, CENTRAL, Embase, Cochrane, ClinicalTrials.gov and Google Scholar databases, as well as scientific session abstracts, were performed. The pooled outcomes included major adverse cardiac events (MACE), mortality, myocardial perfusion, and indices of angina severity (Canadian Cardiovascular Society angina class [CCS] and exercise tolerance). A prespecified subgroup analysis was performed for delivery method, vector, and protein type. The standardized mean difference (SMD) or odds ratio (OR) was calculated to assess relevant outcomes. We assessed heterogeneity using the χ2 and I2 tests. Results: We included 16 RCTs involving 1607 patients (1052 received proangiogenic growth factor therapy and 555 received a placebo or optimal medical therapy). Our analysis showed a significant decreased risk of MACE (OR, 0.72; 95% confidence interval [CI], 0.55-0.93) and significantly improved CCS class (SMD, -0.55; 95% CI, -1.10 to 0.00), but not mortality (OR, 0.66; 95% CI, 0.28-1.54) or exercise tolerance (SMD, 0.47; 95% CI, -0.14 to 1.09), in treated patients compared to those in the control group. Conclusions: Proangiogenic growth factor therapy is a promising treatment option for RFA, with beneficial effects seen on MACE and CCS class. The results of ongoing trials are needed before it can be considered for clinical practice.

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.

Resultados de la terapia con ondas de choque extracorpórea de baja intensidad en pacientes con angina refractaria / Results of low intensity extracorporeal shock wave therapy in patients with refractory angina

RESUMEN Introducción: La terapia con ondas de choque extracorpórea de baja intensidad ha demostrado ser útil en el tratamiento de los pacientes con angina de pecho refractaria. Objetivo: Valorar los resultados de este tipo de terapia en pacientes con angina refractaria al tratamiento farmacológico. Método: Se realizó un estudio cuasiexperimental en 30 pacientes con angina de pecho refractaria a tratamiento, seleccionados de forma no probabilística a partir de los criterios de inclusión. A todos los pacientes se les aplicó terapia con ondas de choque extracorpórea de baja intensidad en el Cardiocentro Ernesto Guevara de Santa Clara, en el período comprendido de enero a diciembre de 2017. Se analizaron variables epidemiológicas, clínicas y ecocardiográficas al inicio del tratamiento y 6 meses después de concluido este. Resultados: Los resultados obtenidos demostraron una mejoría de la clase funcional (CF) de la Canadian Cardiovascular Society (CCS). Previo al tratamiento el 76,7% de los pacientes tenían una CF III y un 23,3% una CF IV, y a los 6 meses de concluida la terapia el 73,3% mejoró a la CF II y solo un 26,7% quedó en CF III. También se evidenció mejoría con respecto a parámetros ecocardiográficos como la motilidad regional y la fracción de eyección del ventrículo izquierdo, la cual, en los hombres, de una media al inicio de la terapia de un 37,81% alcanzó 44,14% a los 6 meses de concluida; y en las mujeres, de una media de 37,11% inicial llegó a 47,22% a los 6 meses después. Conclusiones: El tratamiento con ondas de choque constituye una alterativa terapéutica para los pacientes con angina refractaria.

ABSTRACT Introduction: Low intensity extracorporeal shock wave therapy has proven useful in the treatment of patients with refractory angina pectoris. Objective: To assess the results of this type of therapy in patients with refractory angina to drug treatment. Method: A quasi-experimental study was carried out in 30 patients with refractory angina pectoris to treatment, selected in a non-probabilistic way, taking into account the following inclusion criteria. All patients were applied low intensity extracorporeal shock wave therapy in the Cardiocentro Ernesto Guevara of Santa Clara, in the period from January to December 2017. Epidemiological, clinical and echocardiographic variables were analyzed at the beginning of the treatment and six months after it was completed. Results: The results obtained demonstrated an improvement of the functional class (FC) of the Canadian Cardiovascular Society (CCS). Previous to treatment, 76.7% of patients had a FC III and 23.3% a FC IV, and after six months of completed therapy, 73.3% improved to FC II and only 26.7 % remained in FC III. There was also an improvement with respect to echocardiographic parameters such as regional motility and left ventricular ejection fraction, which, in men, of an average at the start of therapy of 37.81% it reached 44.14% at six months of completed; and in women, of an average of 37.11% initially, it reached 47.22 % six months later. Conclusions: The treatment with shock waves represents a therapeutic alternative for patients with refractory angina.

Aplicación del bloqueo del ganglio estrellado en el tratamiento de dos pacientes con angina refractaria crónica

RESUMEN Objetivo. Evaluación y seguimiento de dos pacientes a los que se les realizó la técnica de Bloqueo del Ganglio Estrellado (BGE) como tratamiento del ángor refractario. Casos clínicos. Se controla durante un período de 12 meses la evolución de dos pacientes con angina crónica refractaria a los que se les realizó la técnica de BGE por abordaje anterior izquierdo bajo fluoroscopía. Durante el control evolutivo se registraron la aparición de episodios anginosos y su relación con la actividad diaria, así como el incremento en el uso de medicación antiisquémica. En ambos casos se logró remisión de la sintomatología sin constatarse complicaciones, permaneciendo libres de síntomas entre dos y tres meses, reiterándose el procedimiento ante la aparición de dolor precordial al esfuerzo. Conclusión. La simpatectomía temporal aparece como una opción efectiva, bien tolerada y de bajo riesgo en pacientes ambulatorios con angina refractaria a tratamiento médico y revascularización, aplicada en el marco de un tratamiento de Cuidado Integral Cardiovascular.

summary Objective. Evaluation and follow-up of two patients whom Stellate Ganglion Blockade (SGB) Technique was performed to treat chronic refractory angina. Clinical cases. We analyzed during a year period two patients with refractory angina despite optimal medication who underwent repeated Stellate Ganglion Block under fluoroscopic guidance by left anterior approach. We recorded the presence or absence of chest pain and the number of anti-angina medications pre and post-treatment. Both patients achieve pain relief without complications. The period of complete pain relief was two and three months for each patient. SGB was repeated when angina returned. Conclusions. Temporal sympathectomy may provide a safe and effective option in patients with angina pectoris that is refractory to optimal medication and revascularization as part of holistic care. Continuous fluoroscopy monitoring may also prevent serious complications.

resumo Objetivo. Avaliação e seguimento de dois pacientes nos quais realizou-se a técnica do Bloqueio do Gânglio Estrelado (BGE) como tratamento da dor anginosa refratária. Casos Clínicos. Controla-se durante um período de 12 meses a evolução de dois pacientes com angina crônica refratária nos quais realizou-se a técnica de BGE por abordagem anterior esquerda sob fluoroscopia. Durante o controle evolutivo registrou-se o aparecimento de episódios anginosos e sua relação com a atividade diária assim como o incremento no uso de medicação anti-isquêmica. Em ambos casos logrou-se remissão da sintomato-logia sem que se constatasse complicações, permanecendo livres de sintomas por 2 a 3 meses, reiterando-se o procedimento ante a aparição de dor pré-cordial ao esforço. Conclusão. A simpatectomia temporal surge como uma opção efetiva, bem tolerada e de baixo risco em pacientes ambulatoriais com angina refratária a tratamento médico e revascularizacão, aplicada no conjunto de um tratamento cardiovascular integral.