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Feasibility of Extracorporeal Shock Wave Myocardial Revascularization Therapy for Post-Acute Myocardial Infarction Patients and Refractory Angina Pectoris Patients.
Myojo, M, Ando, J, Uehara, M, Daimon, M, Watanabe, M, Komuro, I
International heart journal. 2017;(2):185-190
Abstract
Extracorporeal shockwave myocardial revascularization (ESMR) is one of the new treatment options for refractory angina pectoris (RAP), and some studies have indicated its effectiveness. A single-arm prospective trial to assess the feasibility of ESMR using Cardiospec for patients with post-acute myocardial infarction (AMI) and RAP was designed and performed. The patients were treated with 9 sessions of ESMR to the ischemic areas for 9 weeks. The feasibility measures included echocardiography; cardiac magnetic resonance imaging; troponin T, creatine kinase-MB (CK-MB), and brain natriuretic peptide testing; and a Seattle Angina Questionnaire (SAQ) survey. Three post-AMI patients and 3 RAP patients were enrolled. The post-AMI patients had already undergone revascularization with percutaneous coronary intervention (PCI) in the acute phase. In two patients, adverse events requiring admission occurred: one a lumbar disc hernia in a post-AMI patient and the other congestive heart failure resulting in death in an RAP patient. No apparent elevations in CK-MB and troponin T levels during the trial were observed. Echocardiography revealed no remarkable changes of ejection fraction; however, septal E/E' tended to decrease after treatments (11.6 ± 4.8 versus 9.2 ± 2.8, P = 0.08). Concerning the available SAQ scores for two RAP patients, one patient reported improvements in angina frequency and treatment satisfaction and the other reported improvements in physical limitations and angina stability. In this feasibility study, ESMR seems to be a safe treatment for both post-AMI patients and RAP patients. The efficacy of ESMR for post-AMI patients remains to be evaluated with additional studies.
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Use of ranolazine in patients with incomplete revascularization after percutaneous coronary intervention: design and rationale of the Ranolazine for Incomplete Vessel Revascularization Post-Percutaneous Coronary Intervention (RIVER-PCI) trial.
Weisz, G, Farzaneh-Far, R, Ben-Yehuda, O, Debruyne, B, Montalescot, G, Lerman, A, Mahmud, E, Alexander, KP, Ohman, EM, White, HD, et al
American heart journal. 2013;(6):953-959.e3
Abstract
BACKGROUND Incomplete revascularization (ICR) after percutaneous coronary intervention (PCI) is common and is associated with increased rates of rehospitalization, revascularization, and mortality. Adjunctive pharmacotherapy with ranolazine, an inhibitor of the late sodium current with anti-ischemic properties, may be effective in reducing recurrent events after PCI in patients with ICR. TRIAL DESIGN RIVER-PCI is a phase 3, randomized, double-blind, placebo-controlled, international event-driven clinical trial evaluating the efficacy of ranolazine in patients with a history of chronic angina and ICR after PCI. Approximately 2,600 participants with ICR post-PCI will be randomized in a 1:1 ratio to ranolazine or matched placebo within 14 days of an index PCI. The primary end point of the trial is time to the first occurrence of ischemia-driven revascularization or ischemia-driven hospitalization without revascularization. Participants will be followed up for a minimum of 1 year and until at least 720 confirmed primary end point events have occurred. Secondary end points include sudden cardiac death, cardiovascular death, myocardial infarction, and measures of quality of life and cost-effectiveness. The evaluation of long-term safety will include all-cause mortality, stroke, transient ischemic attack, and hospitalization for heart failure. Enrollment commenced in November 2011 and was completed in summer 2013. CONCLUSIONS RIVER-PCI is a novel, large-scale, international, randomized, double-blind, placebo-controlled clinical trial evaluating the role of ranolazine in the long-term medical management of patients with ICR post-PCI.
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Oral administration of L-arginine in patients with angina or following myocardial infarction may be protective by increasing plasma superoxide dismutase and total thiols with reduction in serum cholesterol and xanthine oxidase.
Tripathi, P, Chandra, M, Misra, MK
Oxidative medicine and cellular longevity. 2009;(4):231-7
Abstract
Administration of L-arginine has been shown to control ischemic injury by producing nitric oxide which dilates the vessels and thus maintains proper blood flow to the myocardium. In the present study attempt has been made to determine whether oral administration of L-arginine has any effect on oxidant/ antioxidant homeostasis in ischemic myocardial patients [represented by the patients of acute angina (AA) and acute myocardial infarction (MI)]. L-arginine has antioxidant and antiapoptotic properties, decreases endothelin-1 expression and improves endothelial function, thereby controlling oxidative injury caused during myocardial ischemic syndrome. Effect of L-arginine administration on the status of free radical scavenging enzymes, pro-oxidant enzyme and antioxidants viz. total thiols, carbonyl content and plasma ascorbic acid levels in the patients has been evaluated. We have observed that L-arginine administration (three grams per day for 15 days) resulted in increased activity of free radical scavenging enzyme superoxide dismutase (SOD) and increase in the levels of total thiols (T-SH) and ascorbic acid with concomitant decrease in lipid per-oxidation, carbonyl content, serum cholesterol and the activity of proxidant enzyme, xanthine oxidase (XO). These findings suggest that the supplementation of L-arginine along with regular therapy may be beneficial to the patients of ischemic myocardial syndromes.
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Angina pectoris and atherosclerotic risk factors in the multisite cardiac lifestyle intervention program.
Frattaroli, J, Weidner, G, Merritt-Worden, TA, Frenda, S, Ornish, D
The American journal of cardiology. 2008;(7):911-8
Abstract
Cardiovascular symptom relief is a major indicator for revascularization procedures. To examine the effects of intensive lifestyle modification on symptom relief, we investigated changes in angina pectoris, coronary risk factors, quality of life, and lifestyle behaviors in patients with stable coronary artery disease enrolled in the multisite cardiac lifestyle intervention program, an ongoing health insurance-covered lifestyle intervention conducted at 22 sites in the united states. Patients with coronary artery disease (nonsmokers; 757 men, 395 women; mean age 61 years) were asked to make changes in diet (10% calories from fat, plant based), engage in moderate exercise (3 hours/week), and practice stress management (1 hour/day). At baseline, 108 patients (43% women) reported mild angina and 174 patients (37% women) reported limiting angina. By 12 weeks, 74% of these patients were angina free, and an additional 9% moved from limiting to mild angina. This improvement in angina was significant for patients with mild and limiting angina at baseline regardless of gender (p <0.01). Significant improvements in cardiac risk factors, quality of life, and lifestyle behaviors were observed, and patients with angina who became angina free by 12 weeks showed the greatest improvements in exercise capacity, depression, and health-related quality of life (p <0.05). In conclusion, the observed improvements in angina in patients making intensive lifestyle changes could drastically reduce their need for revascularization procedures.
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The significance of 123I-BMIPP delayed scintigraphic imaging in cardiac patients.
Akashi, YJ, Kida, K, Suzuki, K, Inoue, K, Kawasaki, K, Yamauchi, M, Musha, H, Anker, SD
International journal of cardiology. 2007;(2):145-51
Abstract
BACKGROUND Earlier studies have not fully investigated the significance of radionuclide planar imaging in cardiac patients using the fatty acid analogue 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP). OBJECTIVES This study was to clarify the effectiveness of 123I-BMIPP in assessing the heart-to-mediastinum ratio (H/M) and myocardial washout rate (WR) in patients with heart disease. METHODS Myocardial 123I-BMIPP imaging was performed in 33 patients (20 with chronic heart failure [CHF] and 13 with stable angina pectoris [AP]) and 11 control subjects. Myocardial 123I-BMIPP planner images were obtained 30 min (early image) and 4 h (delayed image) after tracer injection. The left ventricular ejection fraction (LVEF) was measured by quantitative gated single photon emission computed tomography. The concentration of plasma brain natriuretic peptide (BNP) was measured before the scintigraphic study. RESULTS (1) Delayed H/M was much lower in CHF than in AP (1.93 +/- 0.37 vs. 2.21 +/- 0.38, p < 0.05) and controls (vs. 2.47 +/- 0.38, p < 0.001). (2) The WR in CHF and AP were higher than the WR in controls (39.8 +/- 12.7% and 38.7 +/- 11.1 vs. 27.9 +/- 10.2%, p < 0.01 and p < 0.05, respectively). (3) In all subjects, LVEF was correlated with delayed H/M (r = 0.39, p < 0.01). And, the BNP was correlated with both the WR (r = 0.36, p < 0.05) and delayed H/M (r = - 0.29, p = 0.05). CONCLUSION These data strongly suggest that the delayed H/M and myocardial WR of 123I-BMIPP enhances the assessment of the myocardial fatty acid metabolism disorders in patients with heart disease in both masked and unmasked conditions.
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Tolerability to 1-year treatment with once-daily molsidomine in patients with stable angina.
Messin, R, Bruhwyler, J, Dubois, C, Famaey, JP, Géczy, J
Advances in therapy. 2006;(4):601-14
Abstract
Prolonged-release molsidomine 16 mg once daily) QD (has proved effective in the short-term treatment of patients with stable angina. The purpose of this multicenter study was to assess its long-term tolerability and clinical effectiveness. A total of 320 patients with stable angina were treated for 1 year with molsidomine 16 mg QD administered open label as monotherapy or add-on therapy, when beta blockers and/or calcium antagonists were prescribed concomitantly) in 128 patients, ie, 40% of cases), depending on the severity of disease and/or local therapeutic policies. In all, 293 patients (91.6%) completed the study. The proportion of patients who reported drug-related adverse events (AEs) was 9.1%, which is not significantly different (P=.13) from the 5.9% observed during previous short-term (2-4 wk) treatment. Headache accounted for 80.6% of all drug-related AEs and required discontinuation of the drug in one quarter of patients who reported the symptom (ie, 1.9% of the 320 patients involved in the study). No serious drug-related AEs occurred during the study. Tolerability to molsidomine, evaluated with use of a visual analog scale (VAS), improved by 20% from beginning to end of 1-year follow-up. Two-by-two Bonferroni's comparisons were significant at the .05 level between the 2-month assessment and assessments performed at 8, 10, and 12 months. No age-time interaction was noted (P=.82). Heart rate, blood pressure, electrocardiogram, and blood parameters showed no statistically significant or clinically relevant changes during the study. Compliance with treatment was satisfactory throughout the follow-up period. There was no significant change in the weekly frequency of anginal attacks and consumption of short-acting nitroderivatives during the 1-year study (P=.07 and P=.12,respectively), but their frequency was significantly (ie, approximately 50%) lower than during a preceding short-term treatment period (P<.0001 and P=.014, respectively). Subjective clinical status, evaluated through an appropriate VAS, improved by 38% from start to end of 1-year follow-up. Bonferroni's comparisons between baseline and subsequent 2-month evaluations were all significant at the .05 level. No age-time interaction could be seen for frequency of anginal attacks and consumption of short-acting nitroderivatives, nor for clinical status )P=.10, P=.11, and P=.51, respectively). Neither tolerability to molsidomine nor effectiveness of the drug was biased by concomitant antianginal therapies, insofar as none of these parameters showed a significant treatment type (ie, molsidomine administered as monotherapy or add-on therapy)-time interaction (VAS for tolerability: P=.44; angina: P=.39; nitroderivatives: P=.72; VAS for clinical status: P=.62). Molsidomine 16 mg QD administered for 1 y to patients with stable angina was well tolerated and remained effective during the entire treatment period, independent of age and concomitant antianginal therapy.
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Effects of vitamin C on intracoronary L-arginine dependent coronary vasodilatation in patients with stable angina.
Tousoulis, D, Xenakis, C, Tentolouris, C, Davies, G, Antoniades, C, Crake, T, Stefanadis, C
Heart (British Cardiac Society). 2005;(10):1319-23
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Abstract
OBJECTIVE To assess the effects of intravenous vitamin C administration on the vasomotor responses to intracoronary L-arginine infusion in epicardial coronary arteries. METHODS 28 patients with coronary artery disease and stable angina were enrolled in the study. Eight patients received intracoronary infusions of 150 micromol/min L-arginine before and after intravenous infusion of vitamin C, 10 patients received intracoronary infusions of 150 micromol/min L-arginine before and after intravenous infusion of normal saline, and 10 patients received intracoronary normal saline before and after intravenous infusion of vitamin C. The diameter of proximal and distal coronary artery segments was measured by quantitative angiography. RESULTS Infusion of L-arginine caused significant dilatation of both proximal (4.87 (0.96)%, p < 0.01 v normal saline) and distal (6.33 (1.38)%, p < 0.01 v normal saline) coronary segments. Co-infusion of vitamin C and L-arginine dilated proximal coronary segments by 8.68 (1.40)% (p < 0.01 v normal saline, p < 0.01 v L-arginine) and distal segments by 13.07 (2.15)% (p < 0.01 v normal saline, p < 0.01 v L-arginine). Intravenous infusion of vitamin C caused a borderline increase in proximal and distal coronary segment diameters (1.93 (0.76)% and 2.09 (1.28)%, respectively, not significant). CONCLUSIONS L-arginine dependent coronary segment vasodilatation was augmented by the antioxidant vitamin C in patients with coronary artery disease. Thus, vitamin C may have beneficial effects on nitric oxide bioavailability induced by L-arginine.
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Risk score for predicting death, myocardial infarction, and stroke in patients with stable angina, based on a large randomised trial cohort of patients.
Clayton, TC, Lubsen, J, Pocock, SJ, Vokó, Z, Kirwan, BA, Fox, KA, Poole-Wilson, PA
BMJ (Clinical research ed.). 2005;(7521):869
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Abstract
OBJECTIVE To derive a risk score for the combination of death from all causes, myocardial infarction, and disabling stroke in patients with stable symptomatic angina who require treatment for angina and have preserved left ventricular function. DESIGN Multivariate Cox regression analysis of data from a large multicentre trial. SETTING Outpatient cardiology clinics in western Europe, Israel, Canada, Australia, and New Zealand. PARTICIPANTS 7311 patients with all required data available. MAIN OUTCOME MEASURE Death from any cause or myocardial infarction or disabling stroke during a mean follow-up of 4.9 years. RESULTS 1063 patients either died from any cause or sustained myocardial infarction or disabling stroke. The five year risk of this composite ranged from 4% for patients in the lowest tenth of risk to 35% for patients in the highest tenth. The risk score combines 16 routinely available clinical variables (in order of decreasing contribution): age, left ventricular ejection fraction, smoking, white blood cell count, diabetes, casual blood glucose concentration, creatinine concentration, previous stroke, at least one angina attack a week, coronary angiographic findings (if available), lipid lowering treatment, QT interval, systolic blood pressure > or = 155 mm Hg, number of drugs used for angina, previous myocardial infarction, and sex. Fitting the same model separately to all cause death, myocardial infarction, and stroke gave similar results. The risk score did not seem to predict the nature of the event (death in 39%, myocardial infarction in 46%, and disabling stroke in 15%) or the incidence of angiography or revascularisation, which occurred in 29% of patients. CONCLUSION This risk score is an objective aid in deciding on further management of patients with stable angina with the aim of reducing serious outcome events. The score can also be used in planning future trials.
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Matching the evaluation of the clinical efficacy of clopidogrel to platelet function tests relevant to the biological properties of the drug.
Labarthe, B, Théroux, P, Angioï, M, Ghitescu, M
Journal of the American College of Cardiology. 2005;(4):638-45
Abstract
OBJECTIVES This study aimed to explore platelet function tests relevant to the biological effects of clopidogrel that could help the clinical monitoring of drug efficacy. BACKGROUND Clopidogrel selectively inhibits the P2Y12 receptor, the major role of which is stabilization of aggregation, whereas initiation of aggregation depends on activity of both P2Y1 and P2Y12 receptors. METHODS Tests used were peak aggregation (Agg(max)) and late aggregation (Agg(6min)), and disaggregation, relating to P2Y1 and P2Y12 activity, respectively; and monoclonal antibody binding activated glycoprotein (GP) IIb/IIIa receptors (PAC-1) and P-selectin, measuring activation and secretion. A first study compared hirudin/PPACK (r-hirudin and D-phenylalanyl-prolyl-arginine chloromethyl ketone) with citrate as blood anticoagulant (16 patients), and a second control study compared the effects of clopidogrel, aspirin, or both (20 normal controls). RESULTS Clopidogrel similarly inhibited adenosine 5'-diphosphate (ADP)-induced Agg(max) with either anticoagulant, but significantly more Agg(6min) (75% vs. 31%), P-selectin (72% vs. 53%), and PAC-1 (62% vs. 24%) in hirudin/PPACK. In the control study, it inhibited Agg(max) by 22%, and Agg(6min), P-selectin, and PAC-1, by 69%, 66%, and 55%, respectively (all p < 0.05). Disaggregation at six min reached 62% with clopidogrel, but was virtually absent with placebo and aspirin. Non-responsiveness as evaluated by inhibition of Agg(max) in citrate was diagnosed in 35% of patients; in half this rate by Agg(6min), P-selectin, and PAC-1; and in 6% to 12% with the latter tests performed in hirudin/PPACK. CONCLUSIONS The evaluation of clopidogrel responsiveness by platelet function tests is largely influenced by the choice of blood preservative and functional tests. Measures of aggregation stabilization, and of consequent secretion and activation, identified most patients as responders, contrasting with measures of peak aggregation, by likely reflecting better the interactions clopidogrel and the P2Y12 receptor.
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Treatment of angina pectoris: associations with symptom severity.
Kirwan, BA, Lubsen, J, Poole-Wilson, PA, ,
International journal of cardiology. 2005;(2):299-306
Abstract
OBJECTIVE To evaluate whether the frequency of anginal attacks in medically treated patients with stable angina is related to the intensity of anti-anginal treatment, the clinical history and coronary anatomy. METHODS Analysis of baseline data from the A Coronary disease Trial Investigating Outcome with Nifedipine GITS (ACTION) study, an ongoing placebo-controlled trial in 7669 patients with stable angina pectoris who require anti-anginal treatment. RESULTS Prior to randomisation, 8% of 7669 patients had no anginal attacks, 63% had occasional, 22% had regular, 4% had frequent and 3% had daily attacks. Men (79% of all patients) and patients with a history of MI (51%) had less frequent anginal attacks (P<0.0001). The number of coronary angiograms ever performed (70% had at least one angiogram), the extent of angiographic coronary disease (32% of those who had angiography had more than two-vessel disease), a history of peripheral artery disease (12%), the number of anti-anginal drugs used (64% were prescribed two or more such medications) and a history of revascularisation (a history of coronary bypass surgery was present in 23% and of balloon dilatation in 26%) were each positively associated with anginal attack frequency. CONCLUSIONS For the majority of patients with chronic stable angina not on a calcium-antagonist, medical treatment with other anti-anginal drugs is sufficient to control symptoms and only a minority of patients are refractory to medical treatment. Invasive treatments for chronic stable angina are only needed in a small proportion where symptoms persist.