Canadian Cardiovascular Society Class Research Articles

Real-World Data from the Use of Ranolazine in Patients with Stable Angina Pectoris: The RANGER Study.

Background: Although ranolazine has been available for years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on the effectiveness, tolerability, and safety of ranolazine are limited. Methods: A non-interventional, prospective study was conducted to assess the effectiveness and safety of ranolazine. Patients eligible for enrolment had a baseline assessment between one and fourteen days after initiating ranolazine for the first time and a follow-up visit three months later. The primary endpoints comprised the weekly frequency of angina attacks, total adverse events, and ranolazine discontinuation rate. The secondary endpoints included the use of short-acting nitrates, changes on the Canadian Cardiovascular Society (CCS) angina classification score and quality of life scale score (QoL). Results: In total, 1101 patients were enrolled at 214 sites. Mean weekly angina attacks were reduced from 3.6 ± 2.9 to 0.4 ± 0.9 (p < 0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7 ± 2.2 (p < 0.0001). CCS class and QoL were also improved (p < 0.0001). Adverse events were reported by 11 (1%) patients in total, while 2 of them (0.2%) were characterised as serious. Treatment was discontinued for various reasons in 23 patients (2.1%) after the follow-up period. Ranolazine treatment was equally effective in all subgroups tested, with larger benefits observed in patients with more frequent angina and CCS angina class III and IV. Up-titration of ranolazine during the study improved the outcomes. Conclusions: Ranolazine was well tolerated and effectively reduced angina attacks, with simultaneous improvement of the CCS class and QoL score in patients with stable angina.

Percutaneous intramyocardial septal radiofrequency ablation after 5-year follow-up

ObjectiveThe objective is to evaluate the 5-year follow-up results of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for hypertrophic obstructive cardiomyopathy (HOCM), including clinical status, electrocardiographic and echocardiographic characteristics.Methods27 patients (age:...

The Canadian Cardiovascular Society Classification of acute atherothrombotic myocardial infarction provides a novel staging scheme based on tissue injury severity.

The Canadian Cardiovascular Society Classification of acute atherothrombotic myocardial infarction provides a novel staging scheme based on tissue injury severity.

Minimalistic Hybrid Approach for the Percutaneous Treatment of Coronary Chronic Total Occlusions: Midterm Follow-Up of an International Multicenter Cohort

The minimalistic hybrid approach (MHA) is a recently proposed algorithm to perform chronic total occlusion (CTO) percutaneous coronary intervention (PCI), reducing the overall invasiveness of the procedure without impacting the acute results. However, data on midterm results are lacking. This study aimed to evaluate the midterm clinical outcomes of a multicenter international cohort of CTO PCI treated according to the MHA. Data from a consecutive series of patients with a CTO who underwent PCI according to the MHA between February 2019 and March 2022 were prospectively collected in 3 European centers and retrospectively analyzed. The main outcome was the first occurrence of a major adverse cardiac event (MACE), defined as a composite outcome of all-cause death, any myocardial infarction, and target vessel revascularization, at the last follow-up available. A total of 212 patients were included. The majority of the patients were symptomatic for angina (Canadian Cardiovascular Society class 2 or 3: 63.7%) at the time of the index procedure. The mean Japanese-CTO and CASTLE scores were 2.1 ± 1.2 and 2.0 ± 1.3, respectively. Technical success (CTO open with optimal flow) was achieved in 198 patients (93.9%) and procedural success (technical success without in-hospital MACEs) in 195 (91.9%). At the last follow-up available (median 677 days), the cumulative incidence rate of MACEs was 11.5%; in particular, all-cause death was 7.4%, any myocardial infarction was 4.3%, and unplanned target vessel revascularization was 6.5%. In conclusion, the midterm results of the MHA seem to be in line with contemporary results of other CTO PCI algorithms, thus potentially validating the MHA as a valuable alternative, provided that interventionalists are already expert CTO operators and accustomed to the definitions and peculiarities of MHA.

The efficacy of coronary sinus reduction in refractory angina: A meta-analysis

Abstract Objectives Refractory angina is a frequent complain of patients with coronary artery disease. Its management is challenging despite the available pharmacological approaches. Interventional approaches have also been attempted, with coronary sinus reduction (CSR) being the main treatment option. Purpose This meta-analysis aimed to assess the efficacy of CSR in improving symptoms and cardiovascular endpoints in patients with refractory angina. Methods We searched the Pubmed database till 26/2/2023 for studies assessing the impact of CSR in refractory angina. The primary outcome of interest was the improvement in Canadian Cardiovascular Society (CCS) category by at least one class. Secondary outcomes included the implantation success, the proportion of patients improving by at least two CCS classes, as well as the rates of new myocardial infarction/percutaneous coronary intervention and mortality at follow-up. Results The literature search resulted in 190 studies. After screening of title/abstract/full-text, a total of 10 studies (1400 patients) were included in the meta-analysis. The median follow-up was 12.8 months (range: 4-24 months). High rates of implantation success (97%, 95% confidence interval (CI) 95%-98) were reported. Improvement by at least one CCS class was reported by 77% (95% CI 73%-81%). Improvement by at least two CCS classes was seen in 41% (95% CI 36%-47%). The proportion of patients exhibiting a new myocardial infarction/percutaneous coronary intervention was 7% (95% CI 3%-16%), while the mortality rate was 7% (95% CI 3%-14%). Conclusion Coronary sinus reduction is a procedure accompanied by high success rates, and is effective in improving symptoms in a considerable proportion of patients with refractory angina.

Treatment of microvascular angina with the coronary sinus reducer: a first experience

Abstract The Coronary Sinus Reducer (CSR) is an hourglass-shaped device approved for the treatment of refractory angina. Its percutaneous implantation in the coronary sinus leads to a retrograde increase in venous pressure, which is thought to improve capillary recruitment and perfusion to the ischemic myocardium. No data is however available on the use of the CSR to treat microvascular angina, an increasingly recognized but still poorly understood condition. In this preliminary study, we evaluated the efficacy of the CSR in a small cohort of patients with non-obstructive disease. We screened consecutive patients from the prospective COMPLEX registry that received a CSR for refractory angina between June 2018 and November 2022. Inclusion criteria were the absence of obstructive coronary artery disease (&amp;lt;50% narrowing in all coronary arteries, or a negative intracoronary fractional flow reserve test) and no prior history of revascularization. Endpoints were angina and dyspnea symptoms, evaluated with the Canadian Cardiovascular Society (CCS) and the New York Hearth Association (NYHA) scores respectively, procedural success rate, and major adverse cardiovascular events (MACE), defined as a composite of all-cause mortality, cardiovascular death, acute coronary syndromes (ACS) and heart failure (HF) hospitalizations. We ultimately enrolled 8 patients; 6 (75%) were females and mean age was 67.8±9.9 years. Their baseline characteristics are further depicted in table 1. Microvascular dysfunction was invasively confirmed in 5 (62.5%) patients; mean index of microvascular resistance (IMR) was 32.8±15.7 and mean coronary flow reserve (CFR) was 1.7±0.7. In one patient, reduced global CFR (1.4) was evident on cardiac magnetic resonance examination. At baseline, mean CCS class was 2.9±0.6, NYHA class 2±0.9, and number of antianginal drugs 2.6±1.6. Procedural success was 100%, with only one patient experiencing a procedure-related complication (sternocleidomastoid muscle hematoma requiring no intervention). At a median follow-up of 647.5 days (IQR 132-732), mean CCS class was 1.5±0.8, NYHA class 1.9±0.9 and number of antianginal drugs 1.9±1.1. All patients improved by ≥1 CCS class and 3 (37.5%) by ≥2 CCS classes. No MACE was observed. To the best of our knowledge, we present the first report of CSR implantation for the treatment of microvascular angina. Our positive results are particularly promising given the paucity of treatment options currently available for the condition, but larger studies are needed to confirm these findings.table 1figure 1

Angiogenic gene therapy for refractory angina: results of the epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (EXACT) phase 2 trial

Abstract Background Refractory or "no option" angina (RA) is a debilitating condition with increasing global prevalence. Exogenous transduction of vascular endothelial growth factor (VEGF) induces angiogenesis and improves perfusion of ischemic myocardium in preclinical studies. XC001 (AdVEGFXC1) is a novel adenoviral-5 vector expressing the three major isoforms of VEGF (-121, -165, -189) in ratios shown to enhance potency and improve safety. Purpose EXACT is a single-arm, multicenter, open-label, phase 2 trial to explore the safety, tolerability, and preliminary efficacy of trans-epicardial delivery of XC001 to improve exercise capacity and ischemic burden in RA patients. Methods Patients were required to have stable Canadian Cardiovascular Society (CCS) class II-IV angina on maximally tolerated medical therapy with exercise limited by angina after 90 but before 540 seconds on a modified Bruce protocol, demonstrable ischemia on stress positron emission tomography (PET) and lack revascularization options. XC001 (1x1011 viral particles) was injected directly into ischemic myocardium via surgical transthoracic epicardial access. The primary outcome was safety by adverse event monitoring. Efficacy assessments included difference from baseline to six months in total exercise time (TET), myocardial ischemia by PET, angina class, angina frequency, and quality of life. Results Thirty-two patients (mean/median ages of 64/64, 34% female) were enrolled at 13 sites between March 2021 and July 2022. Median anti-anginal use was 3, 75% had prior revascularization with CABG and 88% with PCI. Fifty-five serious adverse events (SAEs) were observed in 21 patients (66%). None were attributed to study drug. Twenty-one SAEs in 14 patients were related to the surgical procedure, all of which were expected. One non-CV death occurred in month 3 following respiratory infection (Covid) deemed unrelated to surgery or study drug. Compared to baseline, total exercise time at 6-months increased by 85.5 seconds (95% CI 31.3-139.7) [Figure 1A] while total myocardial ischemic deficit in the treated region on PET decreased by 14.4% (95% CI, 3.01–25.73) [Figure 1B]. Angina frequency and nitroglycerin use measured during a two-week diary decreased by 6.6 episodes (95% CI, 3.5–9.7) and 4.1 doses (95% CI, 1.3–6.9), respectively. Canadian Cardiovascular Society angina grade decreased from 3.1 to 1.8, mean difference 1.3 classes (95% CI, 1.0–1.6) [Figure 2] while Seattle Angina Questionnaire Frequency score improved from 41.3 to 67.4, mean difference of 26.1 (95% CI, 16.3–35.9). Conclusions VEGF gene therapy with XC001 administered via minimally invasive epicardial delivery appears safe and well tolerated. Improvements in objective and subjective measures including total exercise time, myocardial perfusion, angina frequency and quality of life support a clinically meaningful biologic effect. This therapy warrants study in larger randomized studies.

Changes in myocardial perfusion after coronary sinus reducer implantation for refractory angina - assessment using fully automated quantitative stress perfusion cardiac MRI

Abstract Introduction Previous reports show angina improvement after Coronary Sinus Reducer (CSR) implantation [1,2]. However, the mechanistic basis remains unconfirmed. Preliminary studies using semi-quantitative metrics derived from stress perfusion cardiac MRI (CMR), have suggested improved myocardial perfusion particularly in ischaemic segments [3]. To date, assessment by fully automated quantitative myocardial perfusion CMR has not been reported. Purpose To assess the effect of CSR implantation on quantitative regional myocardial blood flow in patients with refractory angina and advanced coronary artery disease (CAD). Methods Prospective cohort study of patients undergoing CSR implantation. CMR was performed at baseline and median 7 months follow-up. Automated segmentation into a 16-segment American Heart Association model was performed to quantify segmental rest and stress myocardial blood flow (MBF, ml/min/g) and myocardial perfusion reserve (MPR). Rest MBF was corrected for heart rate by dividing by the scan heart rate and multiplying by the mean resting heart rate among all subjects. Wilcoxon matched-pairs sign rank tests were used to compare paired global and segmental perfusion values. A linear mixed-effects model with random slopes and intercepts was used to assess the relationship between baseline segmental MPR and associated change in MPR (ΔMPR) after CSR implantation. Results 12 patients (10M:2F; mean age 67) were included. Median Canadian Cardiovascular Society class was 3. Globally, there was no change in rest (P=0.90), stress MBF (P=0.34) or MPR (P=0.72) from baseline to follow-up. However, ΔMPR was related to the degree of baseline ischaemia (panel A). Segments with baseline MPR&amp;lt;2.45 increased in MPR whereas segments with baseline MPR ≥2.45 experienced a decrease (P=0.003, conditional R2: 0.81). In segments with MPR&amp;lt;2.45 (n=138), median ΔMPR was +0.18 (15.4%; P&amp;lt;0.0001); whereas with MPR≥2.45 (n=52) it was -0.41 (-12.7%; P=0.03; panel B). When assessed by myocardial layer, significant increases in MPR were observed in both subendocardial (+0.19 [15.6%]; P&amp;lt;0.0001) and subepicardial (+0.19 [12.3%]; P&amp;lt;0.0002) segments with baseline MPR&amp;lt; 2.45 (panel C). Conversely, in segments with baseline MPR≥2.45, there was a significant reduction in MPR in the subendocardium (-0.43 [-15.9%]; P=0.04) but not in the subepicardium (-0.36 [-9.90%]; P=0.08; panel D). Conclusion To our knowledge, this is the first study showing changes in quantitative myocardial perfusion after CSR implantation by fully automated inline quantitative perfusion CMR. Our analysis shows a relationship between baseline MPR and change in MPR after CSR implantation, supporting redistribution of perfusion into both subendocardial and subepicardial layers as potential mechanisms of action of CSR. Further studies are needed to confirm these preliminary results.

Abstract 15114: Enhanced External Counter Pulsation for Treatment of Angina With No Obstructive Coronary Artery Disease (ANOCA)

Background: Angina and no obstructive coronary artery disease (ANOCA) is associated with poor outcomes and limited treatment options. Enhanced external counterpulsation (EECP) is a non-invasive treatment that involves applying external inflatable cuffs to the lower extremities to increase blood flow during diastole (diastolic augmentation and increased preload), followed by deflation during systole (decreased afterload). Although EECP is indicated in refractory angina patients, its effectiveness in treating refractory angina in ANOCA patients is relatively unknown and limited to small case series. Objective: Assess the efficacy of EECP treatment in ANOCA patients using Canadian Cardiovascular Society (CCS) angina class, 6-minute walk test (6MWT), Duke Activity Status Index (DASI), Seattle Angina Questionnaire (SAQ), and weekly anginal episodes. Methods: We examined ANOCA patients (defined as £50% stenosis in any major epicardial vessels) with CCS class 3 or 4 angina that completed EECP treatment at 2 large centers. CCS class, 6MWT, DASI, SAQ, and weekly anginal episodes were evaluated pre- and post- EECP treatment, as data was available. A paired Student’s t-test, Wilcoxon signed-rank test, and McNemar’s test were utilized as appropriate. Results: 65 ANOCA patients (63% female; 60±11 years) that completed 35±2 EECP sessions were included. Patients were on 4±2 cardiac medications pre-EECP (78% statin, 52% ACEI/ARB, 62% BBs, 34% CCBs, 48% nitrates, and 53% ranolazine). Post-EECP, 42 patients (65%) had an improvement of 3 1 CCS angina class with 16 (25%) improving by 3 2 classes. Significant improvements in CCS angina severity, 6MWT, DASI, SAQ, and weekly anginal episodes were evident post-EECP ( Table ). Conclusion: In ANOCA patients, EECP therapy reduces CCS angina class and improves exercise tolerance. EECP should be considered in ANOCA patients with refractory angina CCS class 3 or 4 as a part of optimal medical therapy.

Abstract 17136: Prospective Cohort Study for Evaluating the Safety and Efficacy of Mobile, Motorized Enhanced Extracorporeal Counterpulsation in Refractory Angina Patients

Introduction: Enhanced external counterpulsation (EECP) therapy is a potential treatment for refractory angina, which refers to persistent symptoms despite optimal treatment. However, the immobility, cost, and lack of individualized pressure control limit the accessibility and clinical implications of EECP. To address these limitations, a new Mobile, Motorized Enhanced Counterpulsation (MECP) device has been developed. Hypothesis: To investigate efficacy of MECP in improving in angina functional class and exercise tolerance in patients with refractory angina and to validate the consistency in outcomes observed with conventional EECP treatment. Methods: This prospective study enrolled patients with symptomatic refractory angina between September 2020 and December 2022 at two tertiary centers in Korea. Baseline and post-treatment assessments included measurements of angina scale, 6-minute walking test, cardiopulmonary exercise test, and central arterial pressure. Results: The study included 71 patients (70.4% male, median age 66 years). After the 10-hour MECP treatment session, 57.7% of patients showed improvement in angina scale based on Canadian Cardiovascular Society classification, with a significant distribution change from 76.8% to 49.3% in class II and from 21.7% to 5.7% in class III (p&lt;0.001). Furthermore, patients demonstrated an increase of 20 meters in the 6-minute walk distance after MECP treatment (464 meters vs. 484 meters, p&lt;0.001). However, there were no statistically significant differences in the baseline characteristics of patients based on their response to MECP. Conclusion : Our study highlights the substantial benefits of MECP in relieving symptoms for patients with refractory angina and suggests its potential for broader clinical applications which merits further investigation.

Abstract 17001: Enhancing Coronary Functional Angiography: Integrating Doppler-Based Left Circumflex Coronary Flow Reserve in Assessment

Background: Coronary microvascular dysfunction (CMD), predominantly affecting women is associated with poor outcomes and has limited diagnostic options. Coronary functional angiography (CFA) is used for diagnosing CMD in patients with refractory angina and no obstructive coronary artery disease (ANOCA). The assumption is that endothelial-independent CMD is a homogenous disease process, therefore current gold-standard for diagnosis is measure of coronary flow reserve (CFR) in the proximal left anterior descending artery (LAD). However, there is limited data on CFR in the left circumflex (LCx). Objective: Examine the benefits of measuring CFR using Doppler-tipped guide wire in LCx in addition to proximal LAD. Methods: Examined 191 ANOCA patients with Canadian Cardiovascular Society (CCS) class 3 or 4 angina despite optimal medical treatment who underwent CFA for assessment of CMD. CFR measurements were obtained using Doppler-tipped guidewire during the administration of 72 mcg of adenosine in both the proximal LAD and LCx and CFR of &lt;2.5 was used to define CMD. Results: 191 patients underwent CFA including 91% female with a median age of 59 years (IQR: 50, 67). The correlation in CFR measurements between the proximal LAD and LCx was 0.610 (p&lt;0.001). 149 (78%) patients had concordant results including 113 (59%) with abnormal CFRs and 36 (19%) with normal CFRs in both vessels. 12 (6%) had abnormal proximal LAD CFR and normal LCx CFR; and 30 (16%) had an abnormal LCx CFR and normal proximal LAD CFR and would have gone undiagnosed without measuring LCx CFR. Conclusion: The addition of LCx CFR measurement to the current standard CFA protocol using the Doppler guidewire improves diagnosis of CMD in patients. Further studies are needed to evaluate a comprehensive assessment of CMD including measurement of LCx CFR.

Enhanced External Counterpulsation for the Treatment of Angina With Nonobstructive Coronary Artery Disease

Angina and nonobstructive coronary artery disease (ANOCA) is associated with poor outcomes and limited treatment options. Enhanced external counterpulsation (EECP) is a noninvasive treatment that involves applying external inflatable cuffs to the lower extremities to increase blood flow during diastole, followed by deflation during systole. Although EECP is approved for treatment in patients with refractory angina due to obstructive coronary artery disease, its effectiveness in treating patients with ANOCA with refractory angina is limited to small studies. We assessed the efficacy of EECP treatment in patients with ANOCA (defined as ≤50% stenosis in any major epicardial vessels) with refractory anginaby measuring changes in Canadian Cardiovascular Society (CCS) angina class, 6-minute walk test, Duke Activity Status Index (DASI), Seattle Angina Questionnaire 7 (SAQ7), and weekly anginal episodes pre-EECP and post-EECP treatment. A total of 101 patients with ANOCA with CCS class III/IV angina completed a full course of EECP treatment at 2 large EECP centers. In 101 patients with ANOCA the mean age (SD) of 60.6 (11.3) years and 62.4% of the cohort were women. We found significant improvements post-EECP treatment in CCS angina class (mean (SD) 3.4 (0.5) to 2.4 (2.9), p <0.001), 6-minute walk test (median 1200 (IQR 972 to 1411) to 1358 (1170 to 1600), p <0.001), DASI (mean (SD) 15.2 (11.6) to 31.5 (16.3), p <0.001), SAQ7 (mean (DS) 36.2 (24.7) to 31.5 (16.3), p <0.001), and weekly anginal episodes (mean (SD) 5.3 (3.5) to 2.4 (2.9), p <0.001). After EECP treatment, 71 patients (70.3%) had an improvement of ≥1 CCS angina class, including 33 (32.7%) patients improving by ≥2 CCS classes. In conclusion, in patients with ANOCA, EECP therapy reduces CCS angina class and improves exercise tolerance and capacity; and should be considered a part of optimal medical therapy.

The Canadian Cardiovascular Society Classification of Acute Atherothrombotic Myocardial Infarction Based on Stages of Tissue Injury Severity: An Expert Consensus Statement

Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide: it can be minimal in aborted MI or myocardial necrosis can be large and complicated by microvascular obstruction and reperfusion hemorrhage. Established risk scores and infarct classifications help with patient management but do not consider tissue injury characteristics. This document outlines the Canadian Cardiovascular Society classification of acute MI. It is an expert consensus formed on the basis of decades of data on atherothrombotic MI with reperfusion therapy. Four stages of progressively worsening myocardial tissue injury are identified: (1) aborted MI (no/minimal myocardial necrosis); (2) MI with significant cardiomyocyte necrosis, but without microvascular injury; (3) cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, “no-reflow”); and (4) cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. Clinical studies have shown worse remodeling and increase in adverse clinical outcomes with progressive injury. Notably, microvascular injury is of particular importance, with the most severe form (hemorrhagic MI) leading to infarct expansion and risk of mechanical complications. This classification has the potential to stratify risk in MI patients and lay the groundwork for development of new, injury stage-specific and tissue pathology-based therapies for MI.

Effectiveness of Device-Guided Breathing in Chronic Coronary Syndrome: A Randomized Controlled Study.

Chronic coronary syndrome (CCS) is one of the most life-restricting coronary artery diseases, and symptom relief is the main goal in CCS patients who suffer from angina. To assess the potential benefits of device-guided breathing in CCS patients with angina in this randomized, controlled, single-blinded study. Fifty-one patients with CCS received device-guided breathing for 7 days/8 weeks. Exercise capacity [exercise stress test], cardiac function [transthoracic echocardiography], and angina severity [Canadian Cardiovascular Society Classification] were evaluated initially and after the training. Device-guided breathing was performed at the lowest resistance of the device (POWERbreathe® Classic LR) for the control group (n = 17). The low load training group (LLTG; n = 18) and high load training group (HLTG; n = 16) were trained at 30% and 50% of maximal inspiratory pressure. Baseline characteristics were compared using one-way ANOVA and Kruskal-Wallis test. Categorical data were compared using the chi-square test. ANCOVA was performed to compare changes between three groups. A p value < 0.05 was considered statistically significant. Metabolic equivalent values were significantly improved in both HLTG and LLTG groups (p < 0.001, p = 0.003). The Duke treadmill score significantly improved and shifted to low-risk both in the HLTG (p < 0.001) and LLTG (p < 0.001) groups. Angina severity significantly alleviated after the training in both HLTG and LLTG groups (p < 0.001, p = 0.002). An 8-week long program of short-term respiratory muscle training provided positive gains in exercise capacity and angina severity in CCS patients with angina. The effects of long-term training programs on CCS patients should be investigated clinically because of the possibility of helping to decrease the need for invasive treatments.

Chronic remote ischemic conditioning treatment in patients with chronic stable angina (EARLY-MYO-CSA): a randomized, controlled proof-of-concept trial

BackgroundChronic remote ischemic conditioning (CRIC) has been shown to improve myocardial ischemia in experimental animal studies; however, its effectiveness in patients with chronic stable angina (CSA) has not been investigated. We conducted a proof-of-concept study to investigate the efficacy and safety of a six-month CRIC treatment in patients with CSA.MethodsThe EARLY-MYO-CSA trial was a prospective, randomized, controlled trial evaluating the CRIC treatment in patients with CSA with persistent angina pectoris despite receiving ≥ 3-month guideline-recommended optimal medical therapy. The CRIC and control groups received CRIC (at 200 mmHg) or sham CRIC (at 60 mmHg) intervention for 6 months, respectively. The primary endpoint was the 6-month change of myocardial flow reserve (MFR) on single-photon emission computed tomography. The secondary endpoints were changes in rest and stress myocardial blood flow (MBF), angina severity according to the Canadian Cardiovascular Society (CCS) classification, the Seattle Angina Questionnaire (SAQ), and a 6-min walk test (6-MWT).ResultsAmong 220 randomized CSA patients, 208 (105 in the CRIC group, and 103 in the control group) completed the treatment and endpoint assessments. The mean change in MFR was significantly greater in the CRIC group than in the control group (0.27 ± 0.38 vs. − 0.04 ± 0.25; P < 0.001). MFR increased from 1.33 ± 0.48 at baseline to 1.61 ± 0.53 (P < 0.001) in the CRIC group; however, a similar increase was not seen in the control group (1.35 ± 0.45 at baseline and 1.31 ± 0.44 at follow-up, P = 0.757). CRIC treatment, when compared with controls, demonstrated improvements in angina symptoms assessed by CCS classification (60.0% vs. 14.6%, P < 0.001), all SAQ dimensions scores (P < 0.001), and 6-MWT distances (440 [400–523] vs. 420 [330–475] m, P = 0.016). The incidence of major adverse cardiovascular events was similar between the groups.ConclusionsCSA patients benefit from 6-month CRIC treatment with improvements in MFR, angina symptoms, and exercise performance. This treatment is well-tolerated and can be recommended for symptom relief in this clinical population.Trial registration[chictr.org.cn], identifier [ChiCTR2000038649].

Long-term prognostic value of quantitative-flow-ratio-concordant revascularization in stable coronary artery disease

ObjectivesConfirming the prognostic value of global QFR and evaluating the long-term prognosis of QFR-concordant therapy in stable coronary artery disease. BackgroundWire-based functional evaluation of coronary disease is linked to patient's prognosis. Quantitative Flow Ratio (QFR) is a newer index of computational physiology, linked to clinical outcomes and prognosis at 1 year follow-up. Long-term prognosis of QFR-concordant revascularization in stable coronary artery disease is however unknown hitherto. MethodsConsecutive patients with stable coronary disease undergoing coronary angiography were included. Centralized and blinded QFR analysis of three coronary territories was performed. Three vessel QFR (3vQFR) was defined as the sum of the basal QFR of each coronary territory. QFR-concordant revascularization was met if all significant lesions (QFR ≤ 0.80) were revascularized and all non-significant lesions (QFR > 0.80) were not; otherwise, the case was defined as QFR-discordant revascularization. Patient-oriented composite end-point (POCE) of cardiac death, myocardial infarction and unscheduled revascularization was the primary endpoint. ResultsA total of 803 patients from six high-volume centers were included. Canadian Cardiovascular Society (CCS) class II angina was the most frequent (48.9%) clinical presentation. Median of follow-up was 68.8 months. 3vQFR was an independent predictor of POCE (HR 1.79 CI95% 1.01–3.18), with 2.75 as optimal cut-off value, irrespective of the therapy received. QFR-discordant revascularization (QFR+/Revascularization- or QFR-/Revascularization+) was an independent predictor of POCE in multivariate analysis (HR 1.65, CI 95% 1.03–2.64). ConclusionGlobal burden of epicardial coronary atherosclerosis, as evaluated by 3vQFR, as well as QFR-discordant therapy are independent predictors of adverse clinical outcome at long-term follow-up in stable coronary artery disease.

Effect of Coronary Sinus Reducer Implantation on Aerobic Exercise Capacity in Refractory Angina Patients—A CROSSROAD Study

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.

Clinical Outcomes of Cardiac Shockwave Therapy in Severe Coronary Artery Disease Patients after Coronary Artery Bypass Grafting.

Cardiac shockwave therapy (CSWT) is a noninvasive treatment for patients with refractory angina or myocardial ischemia. This study aims to evaluate the potential beneficial effect and safety of CSWT in patients with severe coronary artery disease (CAD) who have undergone coronary artery bypass grafting (CABG).This was a single-arm prospective cohort study. A total of 30 patients with severe CAD who were not suitable for coronary revascularization and who had undergone CABG were enrolled. All patients received CSWT for nine sessions. Evaluation was performed before and after CSWT, including the Canadian Cardiovascular Society (CCS) classification, New York Heart Association (NYHA) classification, 6-minute walk test (6MWT), Seattle Angina Questionnaire (SAQ) score, nitroglycerin dosage, echocardiography, myocardial perfusion imaging (MPI), and safety parameters. All patients were followed up at both 1 month and 9 months after CSWT.After treatment, CSWT significantly improved CCS classification (P < 0.05), NYHA classification (P < 0.05), nitroglycerin dosage (P < 0.001), and 6MWT (P < 0.05) at 1 month and 9 months after CSWT. SAQ score (P < 0.05) and left ventricular ejection fraction (LVEF; P = 0.037) by echocardiography significantly improved at 1 month after CSWT. Significant decreases in summed stress score (SSS), summed difference score (SDS), ischemic area stress, and ischemic area difference by MPI were observed at 1 month and 9 months after CSWT (P < 0.01). There were no changes in safety parameters before and after CSWT.CSWT may have a beneficial effect on improving myocardial perfusion, clinical symptoms, exertional capacity, and quality of life and is a safe alternative treatment for patients with severe CAD who have undergone CABG.

Nutritional Status of Coronary Artery Disease Patients-Preliminary Results.

Malnutrition is a condition that negatively impacts the clinical outcomes of numerous diseases. The aim of this study was to assess the nutritional status of coronary artery disease (CAD) patients and to investigate its relationship with the main clinical aspects of CAD. 50 CAD patients undergoing coronary angiography were enrolled in this study. The nutritional status assessment was based on Nutritional Risk Score 2002 (NRS 2002), body mass index (BMI), and bioelectrical impedance analysis (BIA) measurements. The analysis showed a moderate inverse correlation between NRS 2002 and BIA phase angle measured at 50 kHz (R: -0.31; p = 0.03) and Z200/5 parameter (R: 0.34; p = 0.02). The analysis of CAD clinical parameters showed a significant correlation between NRS 2002 and Canadian Cardiovascular Society (CCS) class (R: 0.37; p = 0.01). Left ventricle ejection fraction (LVEF) was correlated with BMI (R: 0.38; p = 0.02), however further BIA revealed hydration changes as LVEF was correlated to intracellular (ICF) and extracellular fluid (ECF) proportion: positively with ICF (R: 0.38; p = 0.02) and negatively with ECF (R: -0.39; p = 0.02). NRS 2002 and BIA are valuable tools for nutritional status assessment in CAD patients. Malnutrition is related to the severity of CAD symptoms, particularly in women. Maintaining proper nutritional status can have a potentially important role in this group of patients.

Improvement of angina after treating focal coronary artery disease undetected in resting conditions.

A 65-year-old woman without cardiovascular risk factors presented with stable angina Canadian Cardiovascular Society (CCS) Class II. The 7-item Seattle Angina Questionnaire (SAQ-7) indicated frequent angina, moderate physical limitation, and low quality of life for a summary score of 50/100. Coronary CT and invasive angiography revealed severe stenosis in the mid-left anterior descending (LAD) coronary artery with a minimum lumen area (MLA) of 0.9 mm2 and mixed plaque (Figures 1A and B). Intravascular ultrasound (IVUS) confirmed small MLA and 84% plaque burden (Figure 1A, right panels). The resting full-cycle ratio (RFR) was negative (0.93), whereas fractional flow reserve (FFR) was positive (0.75) with a focal pressure step-up in the pullback curve as quantified by a high pullback pressure gradient (PPG) index of 0.79 (Figures 1C and D). The patient underwent percutaneous coronary intervention (PCI) with one drug-eluting stent (Figure 1E). Post-PCI IVUS confirmed good stent expansion. Post-PCI FFR increased to 0.92 without residual focal pressure gradients in the pullback curve (Figure 1F), and normal microcirculation function demonstrated by a coronary flow reserve (CFR) of 7.8 and index of microvascular resistance (IMR) of 16 (Figure 1G). RFR remained unchanged at 0.94. The SAQ-7 at 1-year follow-up showed complete symptoms resolution and improvement in all domains (Figure 1H). A symptomatic patient with obstructive focal epicardial disease yet a negative resting index experienced relief from angina after PCI. This case highlights the usefulness of a comprehensive physiological assessment in cases considered for revascularization, particularly with focal lesions.