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 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.

Is typical angina still prognostically important? The influence of "treatment bias" upon prognostic assessments.

BACKGROUND: Since typical angina has become less frequent, it is unclear if this symptom still has prognostic significance. METHODS: We evaluated 38,383 patients undergoing stress/rest SPECT myocardial perfusion imaging followed for a median of 10.9 years. After dividing patients by clinical symptoms, we evaluated the magnitude of myocardial ischemia and subsequent mortality among medically treated versus revascularized subgroups following testing. RESULTS: Patients with typical angina had more frequent and greater ischemia than other symptom groups, but not higher mortality. Among typical angina patients, those who underwent early revascularization had substantially greater ischemia than the medically treated subgroup, including a far higher proportion with severe ischemia (44.9% vs 4.3%, P < 0.001) and transient ischemic dilation of the LV (31.3% vs 4.7%, P < 0.001). Nevertheless, the revascularized typical angina subgroup had a lower adjusted mortality risk than the medically treated subgroup (HR = 0.72, 95% CI: 0.57-0.92, P = 0.009) CONCLUSIONS: Typical angina is associated with substantially more ischemia than other clinical symptoms. However, the high referral of patients with typical angina patients with ischemia to early revascularization resulted in this group having a lower rather than higher mortality risk versus other symptom groups. These findings illustrate the need to account for "treatment bias" among prognostic studies.

Comparison of clinical outcomes in patients with mixed angina and pure vasospastic angina.

OBJECTIVE: This study investigated differences in clinical outcomes between mixed angina (MA) and pure vasospastic angina (PVA). METHODS: A total of 524 vasospastic angina patients who did or did not have >50% coronary artery stenosis from January 2005 to January 2021 were divided into two groups (Group 1: PVA, N  = 399; Group 2: MA, N  = 125) and then three groups [Group 1: PVA, N  = 399; Group 2: MA without percutaneous coronary intervention (PCI), N  = 67; Group 3: MA with PCI, N  = 58] for assessment. We recorded the incidence of major adverse cardiac and cerebrovascular events (MACCE: the composite of death, myocardial infarction, nonfatal stroke or rehospitalization) during 3-year clinical follow-up. RESULTS: Compared to the PVA group, there were significant differences in MACCE (20.8% vs. 11.8%, P  = 0.011) and rehospitalization (20.0% vs. 9.8%, P  = 0.002) in the MA group. Kaplan-Meier analysis showed that patients in the MA with PCI group had the highest cumulative incidence rate of MACCE during the 3-year follow-up (log-rank P  < 0.001). CONCLUSION: Compared with the PVA patients, MA patients had significantly worse clinical outcomes during long-term follow-up.

The role of physiology in the contemporary management of coronary artery disease.

Coronary physiology assessment, including epicardial and microvascular investigations, is a fundamental tool in the contemporary management of patients with coronary artery disease. Coronary revascularisation guided by functional evaluation has demonstrated superiority over angiography-only-guided treatment. In patients with chronic coronary syndrome, revascularisation did not demonstrate prognostic advantage in terms of mortality over optimal medical therapy (OMT). However, revascularisation of coronary stenosis, which induces myocardial ischaemia, has demonstrated better outcome than OMT alone. Pressure wire (PW) or angiography-based longitudinal coronary physiology provides a point-by-point analysis of the vessel to detect the atherosclerotic pattern of coronary disease. A careful evaluation of this disease pattern allows clinicians to choose the appropriate management strategy.Patients with diffuse disease showed a twofold risk of residual angina after percutaneous coronary intervention (PCI) than those with focal disease. Therefore, OMT alone or coronary artery bypass graft might be considered over PCI. In addition, the post-PCI physiological assessment aims to optimise the result revealing residual myocardial ischaemia. Improvement in post-PCI PW or angiography-based functional indices has been associated with better quality of life and reduced risk of cardiac events and residual angina. Therefore, the information obtained from coronary physiology allows for an optimised treatment strategy, which ultimately leads to improve patient's prognosis and quality of life. This review provides an overview of the latest available evidence in the literature regarding the use of functional assessment of epicardial coronary stenosis in different settings in the contemporary patient-tailored management of coronary disease.

Nonpharmacological interventions for 'no-option' refractory angina patients.

Refractory angina pectoris (RAP) defined as chronic anginal chest pain because of coronary artery disease (CAD) is a major problem. The increase in the number of patients with RAP in recent years is because of the increasing aging population and improved survival rates among patients with CAD. Management of patients with RAP is often extremely challenging. In this review, we present several interventional approaches for RAP, including device therapies, lifestyle intervention, and cell therapies. Some of these treatments are currently used in the management of RAP, whereas other treatments are under investigation.

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.

Influence of enhanced external counterpulsation on endothelial function: a meta-analysis of randomized controlled trials.

OBJECTIVES: Enhanced external counterpulsation (EECP) is an effective and noninvasive treatment for patients with refractory angina and chronic heart failure. However, previous studies evaluating the influence of EECP on endothelial function showed inconsistent results. This systematic review and meta-analysis was conducted to evaluate the effects of EECP on endothelial function measured by brachial artery flow-mediated dilation (FMD). DESIGN: PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials comparing the influence of EECP versus usual care on FMD in adult population. A random-effects model incorporating the potential influence of heterogeneity was used to pool the results. RESULTS: Nineteen studies with 1647 patients were included in the meta-analysis. Compared with usual care or conventional therapy, additional treatment with EECP for 3-7 weeks was associated with a significantly improved FMD (mean difference [MD]: 1.96%, 95% confidence interval [CI]: 1.57-2.36, p < 0.001, I2 = 52%). Subgroup analysis showed consistent results in patients with coronary artery disease and in patients with other diseases (p for subgroup difference = 0.21). Results of meta-regression analysis showed that the mean baseline FMD level was positively correlated with the influence of EECP on FMD (coefficient = 0.42, p < 0.001). Results of subgroup analysis suggested that the increment of FMD following EECP was larger in patients with baseline FMD ≥ 5% (MD: 2.69, 95% CI: 2.27-3.10, p < 0.001; I2 = 15%) compared to those with baseline FMD < 5% (MD: 1.49, 95% CI: 1.13-1.85, p < 0.001; I2 = 0%; p for subgroup difference < 0.001). CONCLUSIONS: EECP may be effective in improving endothelial function measured by FMD.

Unlocking Promising Therapies: Drug-Eluting Stents in Medically Refractory Angina Patients With Myocardial Bridging.

Myocardial bridging (MB) is a congenital variation in which a coronary artery segment tunnels through the myocardium instead of following its usual epicardial route. Although MB is usually diagnosed incidentally and has a good long-term prognosis, it can lead to complications such as angina, myocardial infarction, arrhythmias, and sudden death. This study aimed to evaluate the outcomes of drug-eluting stent (DES) implantation in patients with MB and medically refractory angina. The study included 12 patients with significant MB who did not respond to maximal medical therapy and underwent DES implantation. The patients were followed up for a mean duration of 33 months. The procedural success rate was 92%, with only 1 patient experiencing acute coronary artery rupture during the procedure. During the follow-up period, none of the patients reported angina symptoms, required additional percutaneous coronary intervention, or developed stent thrombosis. One patient (8.3%) died from a non-cardiac cause. The procedure demonstrates a high procedural success rate and leads to favorable long-term outcomes, including the absence of angina symptoms and the avoidance of stent-related complications. In conclusion, this study suggests that DES implantation can serve as an effective treatment option for selected patients with medically refractory angina and significant MB.

In the Cardiac Rehabilitation Era, is There a "No-Option" Refractory Angina Patient?: A Case Report. / Na Era da Reabilitação Cardíaca, Ainda Existem Pacientes Portadores de Angina Refratária "Sem Opção"?: Um Relato de Caso.

Exercise-based cardiac rehabilitation, an effective and safe adjuvant treatment recommended to patients with coronary artery disease, is scarcely applied to patients with refractory angina (RA) due to difficulties related to safety, trainning prescription and their clinical management. This case report presents an instance of a "no-option" patient with RA, who was included in a 12-week exercise program, in sessions consisted of 40 minutes of treadmill aerobic exercise, three times a week, and intensity prescribed between ischemic/angina threshold and ventilatory threshold 1, obtained in the cardiopulmonary exercise test; mild to moderate angina was allowed during training. Furthermore, 15 minutes of moderate-intensity resistance training (large group muscle exercises, two sets of 8 to 12 repetitions) was performed. At the end of the protocol, the patient presented an important improvement in functional performance (VO 2 peak 17.0 ml/kg/min to 27.3 ml/kg/min), angina threshold (HR 68 bpm to 95 bpm), and intensity chest pain (levels 7 to 5) with no clinical adverse events during the period. Exercise-based cardiac rehabilitation was safe, even in the occurrence of angina/ischemia during training, according to tolerability to symptoms and other warning clinical signs.

A reabilitação cardíaca baseada em exercícios, um tratamento adjuvante eficaz e seguro recomendado para pacientes com doença arterial coronariana, é pouco aplicada em pacientes com angina refratária (AR) devido a dificuldades relacionadas à segurança, prescrição do treinamento e o seu manejo clínico. Este relato de caso apresenta um paciente "sem opção" com AR, incluído em um programa de exercícios de 12 semanas de duração, composto de 40 minutos de exercício aeróbico em esteira por sessão, três vezes por semana, e intensidade prescrita entre limiares isquêmicos/anginosos e limiar ventilatório 1, conforme obtidos no teste de exercício cardiopulmonar; angina leve a moderada foi permitida durante o treinamento. Além disso, foram realizados 15 minutos de treinamento de resistência de intensidade moderada (exercícios de grandes grupos musculares, duas séries de 8 a 12 repetições). Ao final do protocolo, o paciente apresentou melhora importante no desempenho funcional (VO 2 máximo de 17,0 ml/kg/min para 27,3 ml/kg/min), limiar anginoso (FC de 68 bpm para 95 bpm) e na intensidade da dor torácica (nível 7 para 5) sem eventos clínicos adversos durante o período. A reabilitação cardíaca baseada em exercícios se mostrou segura, mesmo na ocorrência de angina/isquemia durante o treinamento, de acordo com a tolerabilidade aos sintomas e outros sinais clínicos de alerta.

Diseases of the Coronary Microcirculation: Diagnosis and Treatment.

BACKGROUND: Coronary microvascular dysfunction (CMD) comprises a variety of pathogenic mechanisms that impair the microcirculation of the heart. Clinical studies have shown that 30-50% of patients suffering from myocardial ischemia without significant coronary artery stenosis have CMD. The disease is associated with ele - vated mortality and poor quality of life. Whenever a patient presents with symptoms of angina pectoris and no underlying disease is detected by the usual methods, CMD should be considered a possible cause. METHODS: This review is based on publications retrieved by a selective search in PubMed and on current international guidelines and recommendations of specialty societies. RESULTS: The diagnosis of CMD is based on objective evidence of a microvascular origin of symptoms. The guidelines contain a class IIa recommendation for invasive coronary flow reserve and microvascular resistance measurements. Noninvasive tests such as positron emission tomography and cardiac magnetic resonance imaging are less accurate and are given a class IIb recommendation. No highquality therapeutic trials are available to date, and the treatment of CMD is thus based on that of chronic coronary syndrome. Lifestyle modification is performed to reduce risk factors. Patients with an abnormal coronary flow reserve or elevated microvascular resistance can be treated with an ACE inhibitor or angiotensin receptor blocker. Beta-blockers and calcium channel antagonists can relieve angina pectoris. Statins lower the LDL level and have positive pleiotropic effects. First-line treatment can be supplemented with further medications. CONCLUSION: Approximately 25% of patients with CMD have symptoms that do not respond to intensive treatment with the currently available modalities. New treatments, including interventional therapies, are being studied. Their long-term benefit remains to be assessed and compared to that of the existing methods.

Exercise Training on Anginal Threshold Does Not Improve Endothelial Function in Refractory Angina Patients.

Refractory angina (RA) is a chronic condition of coronary artery disease (CAD). Endothelial function (EF) measured by flow-mediated dilation (FMD) is an important prognostic marker in CAD. Exercise training is a stimulus that improves EF in CAD. However, exercise training effects on EF in RA are unknown. Therefore, we aimed to verify the effects of exercise training on EF in RA. This was a longitudinal, non-randomized clinical study, involving patients with patients limited by angina, aged 45 to 75 years. Patients were prospectively allocated by convenience to either exercise trained (ET) or control group (C). Laboratory analysis, cardiopulmonary exercise test (CPET), and FMD were implemented at inclusion and after 12 weeks of exercise training or clinical treatment period. Exercise training included 60 minutes per session, 3 times a week, including 40 minutes of aerobic exercise on anginal threshold heart rate obtained on the CPET, 15 minutes of resistance training, and 5 minutes of stretching. A total of 38 patients were included (mean age 60 ± 9 years, 22 men); 21 were allocated to the ET and 17 to the C group. Baseline measures showed no differences between groups. After 12 weeks glycated hemoglobin and systolic blood pressure were lower in ET before than ET after (p = 0.004, and p = 0.05, respectively), and exercise time of the CPET was lower in ET before than ET after (p = 0.002). Exercise training did not change FMD. In conclusion, exercise training performed on anginal threshold increases exercise tolerance but causes no changes in EF in patients with RA.

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.

EXACT Trial: Results of the Phase 1 Dose-Escalation Study.

BACKGROUND: New therapies are needed for patients with refractory angina. Encoberminogene rezmadenovec (XC001), a novel adenoviral-5 vector coding for all 3 major isoforms of VEGF (vascular endothelial growth factor), demonstrated enhanced local angiogenesis in preclinical models; however, the maximal tolerated dose and safety of direct epicardial administration remain unknown. METHODS: In the phase 1 portion of this multicenter, open-label, single-arm, dose-escalation study, patients with refractory angina received increasing doses of encoberminogene rezmadenovec (1×109, 1×1010, 4×1010, and 1×1011 viral particles) to evaluate its safety, tolerability, and preliminary efficacy. Patients had class II to IV angina on maximally tolerated medical therapy, demonstrable ischemia on stress testing, and were angina-limited on exercise treadmill testing. Patients underwent minithoracotomy with epicardial delivery of 15 0.1-mL injections of encoberminogene rezmadenovec. The primary outcome was safety via adverse event monitoring over 6 months. Efficacy assessments included difference from baseline to months 3, 6 (primary), and 12 in total exercise duration, myocardial perfusion deficit using positron emission tomography, angina class, angina frequency, and quality of life. RESULTS: From June 2, 2020 to June 25, 2021, 12 patients were enrolled into 4 dosing cohorts with 1×1011 viral particle as the highest planned dose. Seventeen serious adverse events were reported in 7 patients; none were related to study drug. Six serious adverse events in 4 patients were related to the thoracotomy, 3 non-serious adverse events were possibly related to study drug. The 2 lowest doses did not demonstrate improvements in total exercise duration, myocardial perfusion deficit, or angina frequency; however, there appeared to be improvements in all parameters with the 2 higher doses. CONCLUSIONS: Epicardial delivery of encoberminogene rezmadenovec via minithoracotomy is feasible, and up to 1×1011 viral particle appears well tolerated. A dose response was observed across 4 dosing cohorts in total exercise duration, myocardial perfusion deficit, and angina class. The highest dose (1×1011 viral particle) was carried forward into phase 2. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04125732.