Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis

Background: Microvascular dysfunction is known to play a key role in patients with angina and nonobstructive coronary artery disease. We investigated the impact of ranolazine among patients with angina and nonobstructive coronary artery disease. Methods: In this randomized, double-blinded, placebo-controlled pilot trial, 26 patients with angina once weekly or more, abnormal stress test, and nonobstructive coronary artery disease (<50% stenosis by angiography and fractional flow reserve >0.80) were randomized 1:1 to ranolazine or placebo for 12 weeks. Primary end point was ΔSeattle Angina Questionnaire (SAQ) angina frequency score. Baseline and 3 months follow-up SAQ, Duke Activity Status Index scores along with invasive fractional flow reserve, coronary flow reserve (CFR), hyperemic myocardial resistance, and cardiopulmonary exercise testing measurements were performed. Results: No significant differences in ΔSAQ angina frequency scores ( P =0.53) or Duke Activity Status Index ( P =0.76) were observed between ranolazine versus placebo, although patients on ranolazine had lesser improvement in SAQ physical limitation scores ( P =0.02) compared with placebo at 3 months. There were no significant differences in ΔCFR or Δhyperemic myocardial resistance between ranolazine and placebo groups. Patients treated with ranolazine, compared with placebo, had no significant improvement in maximum rate of oxygen consumption measured during incremental exercise (VO 2 max) and peak metabolic equivalents of task. Interestingly, in the ranolazine group, patients with baseline CFR<2.0 demonstrated greater gain in CFR compared with those with baseline CFR≥2.0 ( P =0.02). Conclusions: Ranolazine did not demonstrate improvement in SAQ angina frequency score, invasive microvascular function, or peak metabolic equivalent compared with placebo at 3 months. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02147067.

Program «Smart ECG – ranolazin» - own experience and world approach

Purpose - comprehensive analysis of the world approach of the use of ranolazine in various clinical trials and the introduction of the program "Smart ECG" to assess the effectiveness of ranolazine.Matherial and methods. Evaluation of European guidelines, analysis of global randomized clinical trials of the ranolazine use, presentation of our own trial: we examined 40 patients with Q wave myocardial infarction (STEMI), were instituted basic therapy according to the modern recommendations which contained interventional treatment with restoration of patency of a heart attack-conditioned coronary artery, double antiplatelet therapy, statins, β-adrenergic blocker, angiotensin-converting enzyme inhibitors, aldosterone antagonists with addition of ranolazine (group I, 30 patients diagnosed STEMI), control - group II, 10 patients with STEMI, who received basic therapy without addition of ranolazine. Results. Analysis of clinical trials (CARISA, MARISA, ERICA, TERISA, MERLIN-TIMI, RIVER-PCI, RIMINI-TRIAL) proved the effectiveness of ranolazine as an antianginal and anti-ischemic drugs. The use of own program «Smart ECG» demonstrates the positive effect of ranolazine on STEMI and requires further implementation.Conclusion. In the European Society of Cardiology guidelines of the management of stable angina pectoris, ranolazine is given a class IIa (level of evidence B) recommendation as a second-line treatment to reduce angina frequency and improve exercise tolerance in subjects who cannot tolerate, have contraindications to, or whose symptoms are not adequately controlled by β- adrenergic blockers, calcium channel blockers and long-acting nitrates. In subjects with baseline low heart rate and low blood pressure, ranolazine may be considered as a first-line drug to reduce angina frequency and improve exercise tolerance - class IIa (level of evidence C) recommendation. Own study, which partially reflects the global approach according to the analyzed clinical studies, demonstrates the positive effect of ranolazine for patients with STEMI - analogue scale EQ–VAS indicates a positive effect, positive influence on the markers of electrical myocardial instability: decreasing of the probability of cases of SDNN decrease, depression of QT and maybe increase of ratio of maximum velocity for differentiated T wave.

Abstract 16186: Intravascular Ultrasound-guided Surgical Unroofing in Symptomatic Patients With Myocardial Bridging of the Left Anterior Descending Artery

Introduction: Myocardial bridging (MB) has been shown to cause significant clinical symptoms or adverse cardiac events in patients with no obstructive coronary artery disease. In contrast to medical therapy or stent placement with controversial efficacy, surgical unroofing (supra-arterial myotomy) of MB is considered to directly address the pathology with durable normalization of the altered hemodynamics. In this context, preoperative IVUS assessment can provide a precise map of the MB to guide the unroofing procedure, but it remains unclear if any IVUS parameter is related to the efficacy of this treatment. Methods: We evaluated 94 consecutive patients who underwent MB unroofing with serial (preoperative and 6-month follow-up) angina assessments using the Seattle Angina Questionnaire (SAQ). The primary outcome was the SAQ summary score, obtained by averaging the scores of physical limitation, angina frequency, and quality of life. Preoperative IVUS determined total MB length, halo thickness, arterial compression rate, maximal plaque burden upstream of MB, and septal branches originating in the tunneled LAD segment. Results: In all cases, preoperative IVUS successfully offered a geographic MB map with quantitative characteristics: MB length = 27.5 (20.2 to 40.3) mm, halo thickness = 0.54 (0.41 to 0.75) mm, arterial compression rate = 34 (26 to 43)%, and plaque burden = 34 (20 to 46)% [median (range) for all]. MB unroofing resulted in significant symptomatic improvements across all scales of SAQ (p<0.001 for all) as well as the SAQ summary score (Figure), without any death or major complications. No significant correlation was observed between the preoperative IVUS parameters and the change in SAQ summary score after the surgery. Conclusions: IVUS-guided surgical unroofing safely and effectively achieved significant symptomatic improvements in patients with MB, regardless of the morphologic or morphometric MB characteristics assessed by preoperative IVUS.

Do Myocardial Blush Grade Following Chronic Total Occlusion Recanalization Improve Clinical Outcome of Chronic Coronary Syndromes Patients?

Background : Myocardial blush grade (MBG) is an angiographic parameter to describe the adequacy of myocardial reperfusion. The correlation between myocardial blush and the clinical outcome following chronic total occlusion (CTO) recanalization is still unclear. Our study aimed to investigate the impact of myocardial blush after CTO recanalization on the clinical outcome of CCS patients. Design : A retrospective cohort study was conducted. Patients who underwent CTO recanalization were divided into two groups based on the myocardial blush. Patients were classified as having good myocardial blush (MBG category 2 to 3 or QUBE 0 to 10.2) and poor myocardial blush (MBG category 0 to 1 or QUBE 10.2 to 36.4). The outcome measured was the improvement of angina measured using the Seattle Angina Questionnaire (SAQ) and the reduction of antianginal drug regimens. Results : The follow-up period was ranging from 2 to 24 months following the CTO recanalization procedure. The SAQ for physical limitation (83.86 ± 16.11 vs. 77.92 ± 3.44; p = 0.247), angina frequency (85.27 ± 17.44 vs. 74.76 ± 22.05; p = 0.105), and quality of life (73.24 ± 3.41 vs. 72.82 ± 3.56; p = 0.932) between the two groups was not significantly different. Good myocardial blush was not correlated with the reduction of antianginal drug regimens (10 (52.6) vs. 8 (40); p = 0.639). Conclusion : Myocardial blush post-CTO recanalization was not associated with the improvement of angina symptoms and the reduction of antianginal drug regimens among patients with CCS.

Prognostic factors related to angina frequency and health-related quality of life during the recovery period in patients with acute myocardial infarction: A follow-up study

Background and Objective: Angina frequency (AF) and health-related quality of life (HRQoL) are important outcomes of acute myocardial infarction (AMI) survivors. The aim of this study was to identify the specific characteristics related to the changes of AF and HRQoL among AMI patients after treatment. Methods: We performed a prospective cohort study of 102 AMI patients in Taiwan. Data were collected at baseline and 1 month (T2), 3 months (T3), and 6 months (T4) after treatment. AF was assessed using the Seattle Angina Questionnaire (SAQ). The HRQoL was evaluated with the 12-Item Short-Form Health Survey (SF-12). The generalized estimating equation (GEE) model explored the prognostic factors related to the changes in AF and HRQoL. Results: Patients who received PCI had a reduction of the changes in AF compared with those in non-PCI group from baseline to T2 (B: -15.70, p < 0.05), T3 (B: -21.50, p < 0.05) and T4 (B: -22.91, p < 0.05). Occlusive vessels negatively associated with the changes in physical HRQoL from baseline to T3 (B: -11.44, p < 0.001) and T4 (B: -11.53, p < 0.05). Patients who had longer hospital stay (B: 0.86, p < 0.001) and jobs (B: 5.88, p < 0.05) showed better physical HRQoL from baseline to T3. Patients who were older (B: -4.56, p < 0.05) and unemployment (B: -6.86, p < 0.05) reported worse mental HRQoL. Conclusion: Higher risk AMI patients such as PCI therapy, older age, and occlusive vessels would take care carefully for promoting HRQoL and AF.

Association Between Mental Stress-Induced Inferior Frontal Cortex Activation and Angina in Coronary Artery Disease

Background: The inferior frontal lobe is an important area of the brain involved in the stress response, and higher activation with acute mental stress may indicate a more severe stress reaction. However, it is unclear if activation of this region with stress correlates with angina in individuals with coronary artery disease. Methods: Individuals with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors in conjunction with high resolution positron emission tomography imaging of the brain. Blood flow to the inferior frontal lobe was evaluated as a ratio compared with whole brain flow for each scan. Angina was assessed with the Seattle Angina Questionnaire’s angina frequency subscale at baseline and 2 years follow-up. Results: We analyzed 148 individuals with coronary artery disease (mean age [SD] 62 [8] years; 69% male, and 35.8% Black). For every doubling in the inferior frontal lobe activation, angina frequency was increased by 13.7 units at baseline ( , 13.7 [95% CI, 6.3–21.7]; P =0.008) and 11.6 units during follow-up ( , 11.6 [95% CI, 4.1–19.2]; P =0.01) in a model adjusted for baseline demographics. Mental stress-induced ischemia and activation of other brain pain processing regions (thalamus, insula, and amygdala) accounted for 40.0% and 13.1% of the total effect of inferior frontal lobe activation on angina severity, respectively. Conclusions: Inferior frontal lobe activation with mental stress is independently associated with angina at baseline and during follow-up. Mental stress-induced ischemia and other pain processing brain regions may play a contributory role.

Acupuncture therapy for stable angina pectoris: a systematic review and meta-analysis

Background Stable angina pectoris (SAP) is a common cardiovascular disease, which brings health burden to society. Acupuncture therapy is effective in improving SAP as adjunctive therapy, nevertheless, there were controversies on the effect of acupuncture on disease-affected meridian (DAM), sham acupoints and nonaffected meridian (NAM). This study evaluated the effect of acupuncture on DAM as adjunctive therapy, and the difference in acupuncture on DAM, sham acupoints, and nonaffected meridian NAM. Methods Thirteen online databases were searched from inception to December 2, 2019. Risk of bias and quality of evidence for outcomes were respectively assessed by the Cochrane risk of bias assessment tool and the GRADE approach. RevMan 5.3 was adopted to conduct meta-analysis. Results Thirteen RCTs including 1026 participants were included in this study. Acupuncture therapy could be effective in the improvement of angina severity, ECG results, 6-MWT, SAQ results (physical limitation, angina stability, angina frequency, treatment satisfaction, disease perception), anxiety, HRV (LF, LF/HF), ET, CRP, and reduction of nitroglycerin intake. Acupuncture on DAM could be more beneficial than acupuncture on sham acupoints in aspects of angina severity, 6-MWT, SAQ results (angina stability, angina frequency, treatment satisfaction, disease perception). Compared to acupuncture in NAM, acupuncture on DAM could be more effective in SAQ results (angina stability, angina frequency, treatment satisfaction). Moreover, acupuncture on DAM did not increase the risk of dropout and adverse effect. Conclusions Acupuncture on DAM could effectively improving SAP, and it could be more effective compared with acupuncture on sham acupoints or NAM. However, these conclusions were limited by low-quality of most of included studies. Registration Open Science Framework registration (DOI: 10.17605/OSF.IO/F9DTW).

TREATMENT ADHERENCE AND QUALITY OF LIFE OF PATIENTS WITH STABLE ISCHEMIC HEART DISEASE IN TREATMENT WITH NICORANDIL: INTERRELATION AND INTERACTION (ACCORDING TO THE RESULTS OF THE OBSERVATIONAL STUDY NIKEA)

Aim. To assess quality of life (QoL) and its dynamics during nicorandil treatment in patients with stable ischemic heart disease, to study the relationship of treatment adherence and QoL indicators when treated with nicorandil.Material and methods. Observational program NIKEA included 590 patients with angina pectoris. Seattle Angina Questionnaire (SAQ) was used to assess QoL. Patients completed SAQ at the visit of inclusion (V0) and at the visit after 3 months of observation (V3). Potential and actual adherence to therapy was assessed by medical interviews at visits V0, V1 (1 month of observation) and V3. During the visit V0 417 people (from 590 ones enrolled into the study) completed SAQ (71% response); after 3 months (V3) SAQ was filled in by 454 of 552 people who came to this visit (82% response). According to the results of medical interviews, potential adherence (visit V0) was determined in all 590 patients, actual adherence to nicorandil (visits V1 and V3) was assessed in 552 patients who came to these visits. In accordance with the degree of adherence, all patients were divided into 3 groups: (1) adherent to treatment (taking nicorandil for the first three months), (2) non-adherent (who refused to take nicorandil), and (3) partially non-adherent (who started nicorandil, but for various reasons stopped taking the drug).Results. In all patients, regardless of their adherence to the recommended drug, there was an increase in QoL according to all five scales of the SAQ after 3 months of follow-up. Statistically significant positive dynamics of all SAQ indicators was found only in adherent patients (p<0.0001 for all aspects). Patients, who showed good adherence to nicorandil at V1, had more severe angina at the beginning of treatment (according to “Angina Stability” and “Angina Frequency” indicators). These patients also had lower QoL “Disease Perception” score and more confidence in the doctor (“Treatment Satisfaction” score) than non-adherent patients (p<0.05). In non-adherent patients a mild degree of angina was determined 2 times more often according to “Angina Frequency” indicator (p=0.03).Conclusion. The results of the study confirm the interrelation and mutual influence of the QoL indicators and treatment adherence to nicorandil. Effective treatment with nicorandil in patients with lower health-related QoL indicators could increase treatment adherence. On the other hand, the mild degree of angina, the low level of confidence in the treating doctor, the side effects of the new drug reduce medication adherence of patients, which, as a result, negatively affects the QoL of these patients