Management Of Refractory Angina Research Articles

Son of a Lesser God: The Case of Cell Therapy for Refractory Angina.

In the last decades, various non-pharmacological solutions have been tested on top of medical therapy for the treatment of patients affected by refractory angina (RA). Among these therapeutics, neuromodulation, external counter-pulsation and coronary sinus constriction have been recently introduced in the guidelines for the management of RA in United States and Europe. Notably and paradoxically, although a consistent body of evidence has proposed cell-based therapies (CT) as safe and salutary for RA outcome, CT has not been conversely incorporated into current international guidelines yet. As a matter of fact, published randomized controlled trials (RCT) and meta-analyses (MTA) cumulatively indicated that CT can effectively increase perfusion, physical function and well-being, thus reducing angina symptoms and drug assumption in RA patients. In this review, we (i) provide an updated overview of novel non-pharmacological therapeutics included in current guidelines for the management of patients with RA, (ii) discuss the Level of Evidence stemmed from available clinical trials for each recommended treatment, and (iii) focus on evidence-based CT application for the management of RA.

Abstract P100: Enhanced External Counterpulsation Reduces Central Blood Pressure In Stable Angina Patients: A Meta Analysis

Introduction: Emerging evidence suggests central systolic blood pressure (cSBP) and augmentation index are superior predictors of adverse cardiovascular outcomes as compared to peripheral systolic blood pressure (pSBP). Enhanced external counterpulsation (EECP) is a non-invasive treatment modality approved for the management of refractory angina. The degree of benefit from EECP on central hemodynamics and arterial stiffness remains unknown. This meta-analysis evaluated the effect of EECP on peripheral (office) blood pressure and central hemodynamic parameters. Methods: A comprehensive literature search was conducted in Pubmed, CINAHL, and Cochrane Library databases. All prospective clinical trials assessing the impact of EECP in patients with stable angina and CAD were included. Studies were excluded for not completing a full course of EECP, having a baseline peripheral systolic blood pressure &lt100 mmHg, or not reporting adequate data for analysis. The primary endpoint was the change in cSBP before and after EECP. The change in pSBP, pDBP, cDBP, and augmentation index before and after EECP were also assessed. The weighted mean difference using the DerSimonian and Laird random-effect model was utilized for determining the change in each parameter before and after EECP. Statistical heterogeneity was evaluated using the Egger’s bias statistic. Results: Five studies containing 137 unique patients were included for the cSBP analysis. cSBP was reduced significantly by -7.56 mmHg (95% CI -11.83 to -3.28; Cochrane Q=1.81) post-EECP. In the same set of studies, pSBP was reduced significantly by -9.65 mmHg (95% CI -14.32 to -4.98) post-EECP. pDBP [-4.67 mmHg (95% CI -8.56 to -0.77)] was reduced post-EECP, while no changes were evident in cDBP. Augmentation index was reduced by -3.74% (95% CI -7.05 to -0.43) post-EECP. Two studies included a sham-EECP intervention arm and demonstrated no significant changes in cSBP [0.67 mmHg (95% CI -5.66 to 7.01)] or other parameters. Conclusion: EECP significantly reduced cSBP and pSBP by approximately 8 mmHg and 10 mmHg respectively. EECP also demonstrated a mild improvement in arterial stiffness, which translates to reduced wasted left ventricular energy and myocardial oxygen demand. In patients with stable angina and CAD, EECP exerts beneficial effects in both peripheral and central hemodynamics but whether these benefits are sustained over a longer duration need further exploration.

An evidence-based review of neuromodulation for the treatment and management of refractory angina.

Angina pectoris is defined as substernal chest pain that is typically exacerbated by exertion, stress, or other exposures. There are various methods of treatment for angina. Lifestyle modification and pharmacological management are considered as conservative treatments. If these medications do not result in the resolution of pain, more invasive approaches are an option, like coronary revascularization. Refractory angina (RA) is differentiated from acute or chronic angina based on the persistence of symptoms despite conventional therapies. Overall, the prevalence of RA is estimated to be 5%-15% in patients with coronary artery disease, which can account for up to 1,500,000 current cases and 100,000 new cases in the United States per year. Spinal cord stimulation treatment is a viable option for patients who are suffering from RA pain and are either not candidates for revascularization surgery or are currently not being well managed on more traditional treatments. Many studies show a positive result.

Enhanced external counterpulsation as an effective nonsurgical solution for ischemic heart disease patients

Stable angina is managed primarily through lifestyle advice, medication therapy, and coronary revascularization procedures. Some patients with refractory angina exhibit symptoms that are not optimally controlled with the optimal medication and revascularization options available. Enhanced external counterpulsation (EECP) is a technique that can be used to improve symptoms in chronic stable angina. However, the role of EECP has also been investigated following positive outcomes in patients with both angina and heart failure in multicenter studies. We performed a systematic review of the evidence of the clinical effectiveness of EECP. EECP has been approved by the United States Food and Drug Administration (FDA) for the management of refractory angina (Class IIb). About 200 hospitals across India have adopted this technique. EECP uses three sets of pneumatic cuffs that sequentially contract during diastole, increasing aortic diastolic pressure, augmenting coronary blood flow, and central venous return. EECP improves anginal symptoms and exercise tolerance, and reduces nitroglycerin use in patients with chronic, stable angina. EECP has also been shown to be safe and beneficial in patients with symptomatic stable congestive heart failure. It has been postulated that cardiac benefits of EECP are mediated through vascular endothelial growth factor, and nitric oxide-mediated vasodilatation and angiogenesis. In June 2002, the FDA also approved EECP therapy for heart failure patients. EECP is cost-effective if the observed quality of life benefits are assumed to continue throughout a patient's lifetime. However, there remain uncertainties around the long-term effects of the intervention.

Management of refractory angina: the importance of winning over both hearts and minds

Management of refractory angina: the importance of winning over both hearts and minds

Management of Refractory Angina Pectoris.

With improvements in survival from coronary artery disease (CAD) and an ageing population, refractory angina (RA) is becoming an increasingly common clinical problem facing clinicians in routine clinical practice. These patients experience chronic symptoms in the context of CAD, characterised by angina-type pain, which is uncontrolled despite optimal pharmacological, interventional and surgical therapy. Although mortality rates are no worse in this cohort, patients experience a significantly impaired quality of life with disproportionately high utilisation of healthcare services. It has been increasingly recognised that the needs of RA patients are multifactorial and best provided by specialist multi-disciplinary units. In this review, we consider the variety of therapies available to clinicians in the management of RA and discuss the promise of novel treatments.

Ranolazine in Cardiac Arrhythmia.

Ranolazine utilization in the management of refractory angina has been established by multiple randomized clinical studies. However, there is growing evidence showing an evolving role in the field of cardiac arrhythmias. Multiple experimental and clinical studies have evaluated the role of ranolazine in prevention and management of atrial fibrillation, with ongoing studies on its role in ventricular arrhythmias. In this review, we will discuss the pharmacological, experimental, and clinical evidence behind ranolazine use in the management of various cardiac arrhythmias.

Stereoselective handling of perhexiline: implications regarding accumulation within the human myocardium.

Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. Myocardial uptake of both (+) and (-) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (-) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (-) perhexiline were the plasma concentrations [(+) perhexiline: β = -0.256, p = 0.015; (-) perhexiline: β = -0.347, p = 0.001] and patients' age [(+) perhexiline: β = 0.300, p = 0.004; (-) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (-) perhexiline varied inversely with simultaneous heart rate (β = -0.240, p = 0.015). (1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (-) perhexiline may selectively modulate heart rate reduction.

Temporary sympathectomy in chronic refractory angina: a randomised, double-blind, placebo-controlled trial.

Temporary sympathectomy by injection of bupivacaine at the site of the left stellate ganglion is used in the management of refractory angina at several UK centres. Although patients frequently report significant reduction in symptoms, efficacy has not been established by double-blind, randomised placebo-controlled trial (RCT). To investigate the efficacy of the procedure for the first time by a double-blind RCT. Consecutive patients referred to the authors' National Health Service (NHS) angina centre who were candidates for temporary sympathectomy were invited to participate in a trial. A total of 65 patients were randomised to receive either bupivacaine or saline injections. Identical syringes were prepared remotely, blinding patients and staff from randomisation. Cardiac autonomic function was measured 3 hours pre- and post-injection using new heart rate variability (HRV) analyses. Angina episodes were recorded contemporaneously by patients in study diaries in the 7-day periods pre- and post-injection. In 51 patients suitable for analysis, no significant differences between the active and placebo groups were found in patient-recorded frequency or intensity of angina episodes pre- and post-injection. However, across both groups combined, a significant difference was found in the frequency of angina episodes pre- and post-injection. The reduction in frequency of angina episodes produced by this procedure may not be due to drug pharmacology. It may be a placebo response or due to the mechanical effects of the injection of fluid. There is a need for further work using a larger patient cohort considering both mechanical and psychological factors.

Management of refractory angina in the contemporary era

This editorial refers to ‘Long-term survival in patients with refractory angina’[†][1], by T.D. Henry et al. , on page 2683 Refractory angina pectoris is a debilitating disease characterized by angina resistant to conventional therapies for coronary artery disease including drug therapy, percutaneous coronary interventions, and/or coronary artery bypass grafting. Individuals with refractory angina may suffer severely impaired quality of life, with recurrent and sustained chest pain, poor general health status, psychological distress, impaired role functioning and productivity, and restricted ability to perform activities. The European Society of Cardiology (ESC) Joint Study group on the Treatment of Refractory Angina emphasized that refractory angina is a clinical diagnosis (i.e. based on a combinations of history, physical examination, and investigations) and states that refractory angina pectoris is a chronic condition characterized by the presence of angina caused by coronary insufficiency in the presence of coronary artery disease which cannot be controlled by a combination of medical therapy, angioplasty, and coronary bypass surgery.1 The presence of reversible myocardial ischaemia should be clinically established to be the cause of the symptoms. Chronicity is defined as a duration of >3 months. The ESC Joint Study group further states that the diagnosis of refractory angina requires a cardiological and cardiothoracic surgical assessment that the patient has angina of ischaemic origin and that revascularization is not feasible. Despite these robust definitions, the … [1]: #fn-2

Clinical and research issues regarding chronic advanced coronary artery disease: Part I: Contemporary and emerging therapies

The following report is based on a working group meeting about advanced coronary artery disease for patients with refractory ischemia who cannot receive revascularization. The aims were to review currently available treatment strategies, define unmet clinical needs, explore clinical trial design issues, and identify promising novel therapeutic targets and approaches for patients with chronic ischemia. The Working Group brought together medical experts in the management of refractory angina with representatives from regulatory agencies, Centers for Medicare and Medicaid Services, and industry. The meeting began with presentations reviewing the limitations of the current medical therapies and revascularization strategies and focused on lessons learned from past therapeutic attempts to optimize outcomes and on what are considered to be the most promising new approaches. Perspectives from clinical experts and from regulatory agencies were juxtaposed against needs and concerns of industry regarding development of new therapeutic strategies. This report presents the considerations and conclusions of the meeting on December 4-5, 2006. This document has been developed as a 2-part article, with contemporary and emerging therapies for advanced coronary artery disease reviewed first. Trial design, end points, and regulatory issues will be discussed in the second part of the article.

New therapeutic option for cardiac ischemia in transplant vasculopathy: spinal cord stimulation

The main limitation to long-term survival for allogeneic heart transplant recipients is the onset of “accelerated allograft coronary artery disease” (ACAD). Over the years, different treatment options for the management of ACAD-induced critical ischemia have been taken into consideration. The use of percutaneous transluminal coronary angioplasty (PTCA) is still controversial, performed mostly for Type B/C and Type A lesions measuring 2.5 mm. According to Musci et al, there is no difference between PTCA-treated and non–PTCAtreated patients with ACAD. Myocardial re-vascularization surgery is burdened with high peri-operative mortality and poor long-term results. Transmyocardial laser re-vascularization initially provided encouraging short-term results, but these were not borne out by long-term outcome. In consideration of the increasing number of potential heart transplant recipients and the limited donors pool, which is not increasing proportionally, re-transplantation does not appear to be an ethically sufficient option, because a second transplantation entails a far higher short-term mortality than a first transplantation and is accompanied by a high probability of coronary artery disease (CAD) recurrence. The good outcome reported in the literature and our own experience since 1986 in the management of refractory angina with spinal cord stimulation (SCS) has led us to use this technique in posttransplantation CAD as well. To our knowledge SCS treatment for cardiac transplant recipients has not been reported to date. The Brussels Consensus Statement on SCS in 1998 stated that “to be accepted for SCS treatment, angina pectoris must be refractory both to drug therapy (beta-blockers, calcium channel antagonists, long action nitrates, aspirin) and revascularization methods.” We report a 32-year-old man (weight 58 kg, height 168 cm) who underwent orthotopic cardiac transplantation in February 1992 because of dilated cardiomyopathy, which was diagnosed 2 years earlier and probably had a viral etiology. Post-transplantation follow-up revealed hyperlipoproteinemia, hyperuricemia with sporadic episodes of gout, and obesity. During the 4 years after surgery the patient’s tolerance to the allograft was good. Following the onset of diastolic hypertension and atypical chest pain, left cardiac catheterization with coronary angiography was performed in July 1996. Hemodynamic study showed lesion-free coronary arteries. In January 2000 the patient’s weight increased to 97 kg. Also, he complained of chest pain, typical of exercise-induced angina. The pain was “band-like,” retrosternal, with short duration, and decreased at rest (CCS Functional Class II to III). One month From the Divisions of Pain Therapy and Palliative Care, and Cardiac Surgery, University of Turin, Turin, Italy. Submitted June 11, 2002; revised February 13, 2003; accepted February 13, 2003. Reprint requests: Paolo Centofanti, MD, Divisione di Cardiochirurgia, Ospedale Molinette, C.so A.M. Dogliotti 14, 10126 Turin, Italy. E-mail: paolocentofanti@tiscalinet.it Copyright © 2004 by the International Society for Heart and Lung Transplantation. 1053-2498/04/$–see front matter doi:10.1016/S1053-2498(03)00151-7

Chronic Pain: Management Strategies That Work

Chronic Pain: Management Strategies That Work