Search Results (32)

Background: Recent observational studies suggest that coronary sinus reducer (CSR) implantation may have a beneficial effect on microcirculatory indices in patients with coronary microvascular dysfunction (CMD). However, to date, there is no comprehensive summary of the evidence regarding the impact of CSR in this population. Methods: This systematic review was conducted in accordance with the PRISMA 2020 Statement. The following databases were searched: PubMed, EMBASE, MEDLINE, and ClinicalTrials.gov. Studies assessing microcirculatory indices or primarily involving patients with CMD undergoing CSR implantation were included. Results: After the selection process, 17 studies or trials were included in this systematic review. Across observational studies and case series, CSR implantation was associated with significant improvements in coronary microvascular function, including reductions in the index of microvascular resistance and an increase in coronary flow reserve. These physiological changes were accompanied by consistent improvements in angina severity (CCS class), exercise capacity, and quality-of-life measures, particularly in patients with more severe baseline CMD. Evidence was derived mainly from non-randomized studies involving small patient cohorts, with low procedural complication rates. Ongoing randomized trials are expected to clarify the magnitude of benefit and its clinical relevance in this population. Conclusions: CSR implantation may offer clinical and physiological benefits in patients with refractory angina due to CMD. However, the lack of randomized evidence and uncertainty regarding long-term effects warrant further adequately powered trials. Full article

A substantial proportion of patients with ischemic heart disease continue to experience recurrent or persistent angina despite optimized medical therapy and prior revascularization, highlighting the need for novel and effective treatment strategies. Device-based therapies have emerged as promising options to address this unmet clinical need. Among these, the Coronary Sinus Reducer™ (CSR) has gained particular attention, supported by randomized trials and registries demonstrating improvements in angina symptoms and quality of life, with a favorable safety profile. However, a disconnect between symptomatic relief and objective measures of myocardial perfusion has been noted, suggesting that the underlying mechanisms remain incompletely understood. Beyond the CSR, other device-based approaches—such as enhanced external counterpulsation, neuromodulation, and shockwave therapy—are either approved or under investigation. This review explores the current landscape of device-based therapies for angina, focusing on the evidence supporting the CSR and other device-based interventions. We discuss pathophysiological mechanisms, clinical outcomes, and future research directions aimed at optimizing therapeutic efficacy. Integrating patient-reported outcomes with physiological and imaging assessments will be essential to refine indications and improve long-term results. Device-based therapies represent a developing frontier in angina management, with the potential to improve outcomes in patients with persistent symptoms despite optimal medical and interventional therapy. Full article

Background: Ischemia with no obstructive coronary artery disease (INOCA) is characterized by myocardial ischemia in the absence of significant coronary artery stenosis. Despite the lack of major obstructive lesions, patients often present with chest pain, making diagnosis and management a significant challenge. Materials and Methods: A comprehensive search strategy of electronic databases (2000 to 2024) was used to identify studies assessing pathophysiology, diagnosis, surgical treatments, interventions, and outcomes in INOCA. Clinical trials, observational studies, case-control studies, and cohort studies were included. Results: Emerging surgical treatments may have a role in certain subgroups of INOCA patients, particularly those with severe and persistent symptoms or underlying pathophysiological factors that do not respond adequately to pharmacological therapies. Transmyocardial revascularization (TMR) and sympathetic denervation procedures reduce coronary vasospasm in refractory angina. Trials have shown promise for coronary sinus occlusion. Autologous stem cell therapy is an innovative surgical approach that has shown promise in early trials but remains investigational. Selective surgical cardiac vein retroperfusion remains largely experimental, with limited clinical data. Conclusions: This review highlights the need for ongoing research and clinical trials to assess the effectiveness of surgical and nonsurgical options in INOCA. Although current data on surgical interventions is limited, these treatments may offer hope for patients with refractory symptoms. A personalized and multidisciplinary approach to management is essential for optimal patient outcomes. Full article

Refractory angina pectoris (RAP) is a clinical syndrome characterized by persistent chest pain caused by myocardial ischemia that is unresponsive to optimal pharmacological therapy and revascularization procedures. Spinal cord stimulation (SCS) has emerged as a promising therapeutic option for managing RAP, offering significant symptom relief and improved quality of life. A systematic literature review was conducted to evaluate the clinical effectiveness, mechanisms of action, and safety profile of SCS in treating RAP. Comprehensive searches were performed in PubMed, Scopus, and Web of Science for studies published between 1990 and 2023. Of 328 articles identified, 6 met the inclusion and exclusion criteria for final analysis. The included studies consistently demonstrated that SCS significantly reduces the frequency of anginal episodes and nitroglycerin use while improving exercise capacity and quality of life. Proposed mechanisms include modulation of pain signals via the gate control theory, enhancement of autonomic balance, and redistribution of myocardial perfusion. Novel stimulation modalities, including high-frequency, Burst, and Differential Target Multiplexed (DTM), show potential advantages in enhancing patient comfort and clinical outcomes. Nevertheless, long-term studies are necessary to validate these findings and establish the comparative efficacy of these advanced technologies. SCS is a safe and effective therapy for patients with RAP who are unsuitable for surgical interventions. Innovations in neurostimulation, including closed-loop systems and personalized treatment strategies have the potential to further optimize outcomes. Rigorous clinical trials are needed to consolidate the role of SCS as a cornerstone therapy for the management of RAP. Full article

Gender medicine has increasingly underscored the necessity of addressing sex-based differences in disease prevalence and management, particularly within cardiovascular conditions and drug intolerance. Women often present cardiovascular diseases distinctively from men, with a higher prevalence of non-obstructive coronary artery disease and varied ischemic manifestations, such as coronary microvascular dysfunction and epicardial or microvascular coronary spasm. This disparity is further exacerbated by elevated drug intolerance rates among women, influenced by hormonal, genetic, and psychosocial factors. The 2024 ESC guidelines for managing chronic coronary syndromes stress the need for personalized approaches to treat angina and ischemia with non-obstructive coronary artery disease (ANOCA/INOCA), recommending a combination of antianginal medications. Despite standard treatments, up to 40% of ANOCA/INOCA patients experience refractory angina, necessitating a multifaceted approach that often involves multiple antianginal drugs, which can increase the likelihood of drug intolerances. Future research should focus on including women in drug studies and addressing sex-specific differences, while healthcare providers must be equipped to manage gender-specific drug intolerances. Enhanced awareness, individualized treatment strategies, and gender-sensitive healthcare policies are crucial for improving outcomes and bridging the gender gap in cardiovascular medicine. Full article

Adult stem cell therapy via intramyocardial injection of autologous CD34+ stem cells has been shown to improve exercise capacity and reduce angina frequency and mortality in patients with refractory angina (RA). However, the cost of such therapy is a limitation to its adoption in clinical practice. Our goal was to determine whether the less costly, less invasive, and widely accessible, FDA-approved alternative treatment for RA patients, known as enhanced external counterpulsation (EECP), mobilizes endogenous CD34+ stem cells and whether such mobilization is associated with the clinical benefits seen with intramyocardial injection. We monitored changes in circulating levels of CD34+/CD133+ and CD34+/KDR+ cells in RA patients undergoing EECP therapy and in a comparator cohort of RA patients undergoing an exercise regimen known as cardiac rehabilitation. Changes in exercise capacity in both cohorts were monitored by measuring treadmill times (TT), double product (DP) scores, and Canadian Cardiovascular Society (CCS) angina scores between pre- and post-treatment treadmill stress tests. Circulating levels of CD34+/CD133+ cells increased in patients undergoing EECP and were significant (β = −2.38, p = 0.012) predictors of improved exercise capacity in these patients. CD34+/CD133+ cells isolated from RA patients could differentiate into endothelial cells, and their numbers increased during EECP therapy. Our results support the hypothesis that mobilized CD34+/CD133+ cells repair vascular damage and increase collateral circulation in RA patients. They further support clinical interventions that can mobilize adult CD34+ stem cells as therapy for patients with RA and other vascular diseases. Full article

Background: The coronary slow flow phenomenon (CSFP) is an angiographic finding characterised by the delayed passage of contrast through the coronary arteries, despite the absence of obstructive coronary artery disease (defined as less than 50% narrowing of the vessel lumen). Patients with the CSFP experience recurrent angina, for which there are limited evidence-based therapies. Ticagrelor may serve as an effective anti-anginal therapy for these patients by increasing adenosine levels, which could alleviate coronary microvascular dysfunction and its associated angina due to its vasodilatory properties. This study aimed to determine the anti-anginal efficacy of ticagrelor 90 mg taken twice daily on spontaneous angina episodes in patients with refractory angina (i.e., episodes ≥3/week despite two anti-anginals) and documented CSFP. Methods: In a randomised, double-blind, placebo-controlled, cross-over trial, the anti-anginal efficacy of a 4-week ticagrelor therapy regimen was evaluated in 20 patients with refractory angina (mean age 61.5 ± 10.5 years; 40% women) who had documented slow coronary flow. The primary endpoint was the frequency of angina episodes, recorded using an angina diary. Secondary endpoints included the duration and severity of angina episodes, consumption of short-acting nitrates, and health status evaluations using the Seattle Angina Questionnaire (SAQ) and the Short Form-36 (SF-36) indices. Results: During the four weeks of therapy, ticagrelor did not significantly improve angina symptoms compared to the placebo (placebo 25.7 (16.7)) vs. ticagrelor 19.8 (18.1), p > 0.05). Furthermore, it did not impact other patient-related outcome measures, including angina severity, duration, frequency of prolonged angina episodes, nitrate consumption, or the SAQ/SF-36 health outcome indices. No serious adverse events related to the study drug were observed. Conclusions: In patients with documented CSFP who were unresponsive to standard anti-anginal therapy, ticagrelor did not reduce the frequency of spontaneous angina episodes or the consumption of nitrates. Further confirmation of the potential benefits of this therapy may be obtained through a larger clinical trial. Full article

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. Full article

Background: Patients with coronary microvascular disorders often experience recurrent angina for which there are limited evidence-based therapies. These patients have been found to exhibit increased plasma levels of endothelin; thus, selective endothelin–A (Et-A) receptor blockers such as zibotentan may be an effective anti-anginal therapy in these patients. The study evaluated the impact of a 10 mg daily dose of zibotentan on spontaneous angina episodes in patients with the coronary slow-flow phenomenon who had refractory angina (i.e., experiencing angina at least three times/week despite current anti-anginal therapy). Methods: Using a randomized, double-blind, placebo-controlled, crossover trial design with 4-week treatment periods, 18 patients (63.2 ± 9.9 years, 33% females) were recruited. The primary endpoint was angina frequency as measured by an angina diary, with secondary endpoints including nitrate consumption, angina duration/severity and the Seattle Angina Questionnaire (SAQ) domains. Results: During the 4 weeks of therapy, angina frequency significantly improved with zibotentan therapy (placebo 41.4 (58.5) vs. zibotentan 29.2 (31.6), p < 0.05), and sublingual nitrate consumption significantly reduced (placebo 11.8 (15.2) vs. zibotentan 8.8 (12.9), p < 0.05. Conclusions: Zibotentan improved the frequency of spontaneous angina episodes and reduced sublingual nitrate consumption in patients unresponsive to standard anti-anginal therapy. Full article

Ivabradine is a recently introduced inhibitor of the I_f ion channel, which exhibits the capacity to reduce heart rate while preserving hemodynamic stability. At present, ivabradine finds its clinical indication in patients suffering from heart failure with reduced ejection fraction and maintaining a relative sinus rhythm refractory to beta-blockers. To optimize heart rate control, it is recommended to pursue an aggressive up-titration of ivabradine. This approach may ameliorate tachycardia-induced hypotension by incrementally enhancing cardiac output and allow further up-titration of agents aimed at ameliorating heart failure, such as beta-blockers. Both the modulation of heart rate itself and the up-titration of agents targeting heart failure lead to cardiac reverse remodeling, consequently culminating in a subsequent reduction in mortality and morbidity. A novel overlap theory that our team proposed recently has emerged in recent times. Under trans-mitral Doppler echocardiography, the E-wave and A-wave closely juxtapose one another without any overlapping at the optimal heart rate. Employing echocardiography-guided ivabradine for heart-rate modulation to minimize the overlap between the E-wave and A-wave appears to confer substantial benefits to patients with heart failure. This approach facilitates superior cardiac reverse remodeling and yields more favorable clinical outcomes when compared to those patients who do not receive echocardiography-guided care. The next pertinent issue revolves around the potential expansion of ivabradine’s clinical indications to encompass a broader spectrum of diseases. It is imperative to acknowledge that ivabradine may not yield clinically significant benefits in patients afflicted by heart failure with preserved ejection fraction, acute heart failure, sepsis, or stable angina. An important fact yet to be explored is the clinical applicability of ivabradine in patients with atrial fibrillation, a concern that beckons future investigation. In this review, the concept of overlap theory it introduced, along with its application to expand the indication of ivabradine and the overlap theory-guided optimal ivabradine therapy. Full article

Background: Microvascular disorders represent an uncommon site of tissue hypo-perfusion and damage. Various genetic and acquired causes can be involved. A 65-year-old man was admitted because of refractory angina, which he had had since the age of 30 years, micro-hematuria, and recurrent transitory ischemic attacks from the age of 64. Methods: Hematochemical studies, ECG, Holter monitoring, 2D-echo, cardiac magnetic resonance (CMR), CTA of cerebral vessels, endomyocardial coronary angiography, and kidney biopsy processes were undertaken. Gene mutation analysis was conducted using next-generation sequencing, which included more than 5000 genes associated with inherited diseases. Results: Hematochemical findings were unremarkable. The ECG, Holter, 2D-echo, and CTA of brain vessels were normal. Cerebral magnetic resonance showed the presence of multiple small foci of ischemia. Coronary and ventricular angiography showed normal arteries with remarkably slow flow and multiple biventricular micro-aneurysms. At the endomyocardial biopsy, five of seven arterioles presented severe lumen obstruction due to hypertrophy and disarray of the muscular coat. Similarly, obstructed pre-glomerular arteries with glomerular sclerosis were seen at the renal biopsy. Genetics identified mutations in the ABCC6, MMP2, and XYLT1 genes, which play pivotal roles in the extracellular matrix. Conclusion: This study described a new genetic microvascular obstructive disease causing progressive hypo-perfusion of the human brain, heart, and kidney. Full article

Coronary artery bypass grafting (CABG) is the gold standard procedure for multi vessels and left main coronary artery disease. The prognosis and survival outcomes of CABG surgery are highly dependent on the patency of the bypass graft. Early graft failure which can occur during or soon after CABG remains a significant issue, with reported incidences of 3–10%. Graft failure can lead to refractory angina, myocardial ischemia, arrhythmias, low cardiac output, and fatal cardiac failure, emphasizing the importance of ensuring graft patency during and after surgery to prevent such complications. Technical errors during anastomosis are among the leading causes of early graft failure. To address this issue, various modalities and techniques have been developed to evaluate graft patency during and after CABG surgery. These modalities aim to assess the quality and integrity of the graft, thus enabling surgeons to identify and address any issues before they lead to significant complications. In this review article, we aim to discuss the strengths and limitations of all available techniques and modalities, with the goal to identify the best modality for evaluating graft patency during and after CABG surgery. Full article

Coronary sinus reducer (CSR) implantation is a new treatment option for patients with refractory angina pectoris. However, there is no evidence from a randomized trial that would show an improvement in exercise capacity after this treatment. The aim of this study was to evaluate the influence of CSR treatment on maximal oxygen consumption and compare it to a sham procedure. Twenty-five patients with refractory angina pectoris (Canadian Cardiovascular Society (CCS) class II–IV) were randomized to a CSR implantation (n = 13) or a sham procedure (n = 12). At baseline and after 6 months of follow-up, the patients underwent symptom-limited cardiopulmonary exercise testing with an adjusted ramp protocol and assessment of angina pectoris using the CCS scale and Seattle angina pectoris questionnaire (SAQ). In the CSR group, maximal oxygen consumption increased from 15.56 ± 4.05 to 18.4 ± 5.2 mL/kg/min (p = 0.03) but did not change in the sham group (p = 0.53); p for intergroup comparison was 0.03. In contrast, there was no difference in the improvement of the CCS class or SAQ domains. To conclude, in patients with refractory angina and optimized medical therapy, CSR implantation may improve oxygen consumption beyond that of optimal medical therapy. Full article

Balloon pumps are employed to assist cardiac function in cases of acute myocardial infarction, ventricular arrhythmias, cardiogenic shock, unstable angina, refractory ventricular failure, or cardiac surgery. Counterpulsation, through increasing the diastolic pressure and reducing the systolic pressure, increases coronary perfusion and assists the heart to pump more blood at each contraction. An expanding-contracting balloon, modifying the Poiseuille flow in a straight circular duct, is examined in this study. The balloon is spheroid-shaped, with the length of its minor axis, which is perpendicular to the flow direction, changing in time following a sinusoidal law. The inlet flow volume rate is steady while the rate that the fluid volume leaves the duct varies in time due to the presence of the balloon. For a pulsation frequency of 60 pulses/min, the pressure difference across the pulsating balloon exhibits significant phase lagging behind the outflow volume waveform. The outlet pressure depends on the balloon radius oscillation amplitude and is computed for a range of such. The flow field around the spheroid, periodically expanding-contracting balloon in the steady flow stream is presented, in which the exact pattern of the gradual downstream intensification of the flow pulsation alongside the spheroid body is also identified. Full article

Angina is the main symptom of ischemic heart disease; mirroring a mismatch between oxygen supply and demand. Epicardial coronary stenoses are only responsible for nearly half of the patients presenting with angina; whereas in several cases; symptoms may underlie coronary vasomotor disorders; such as microvascular dysfunction or epicardial spasm. Various medications have been proven to improve the prognosis and quality of life; representing the treatment of choice in stable angina and leaving revascularization only in particular coronary anatomies or poorly controlled symptoms despite optimal medical therapy. Antianginal medications aim to reduce the oxygen supply-demand mismatch and are generally effective in improving symptoms; quality of life; effort tolerance and time to ischemia onset and may improve prognosis in selected populations. Since antianginal medications have different mechanisms of action and side effects; their use should be tailored according to patient history and potential drug-drug interactions. Angina with non-obstructed coronary arteries patients should be phenotyped with invasive assessment and treated accordingly. Patients with refractory angina represent a higher-risk population in which some therapeutic options are available to reduce symptoms and improve quality of life; but robust data from large randomized controlled trials are still lacking. Full article