Canadian Cardiovascular Society Angina 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.

Enhanced external counterpulsation increases coronary flow reserve in coronary microvascular disease.

To investigates the outcomes of enhanced external counterpulsation (EECP) among coronary microvascular disease (CMD) patients. Coronary microvascular disease patients were separated into the EECP (n=41) and control cohorts (n=42). Prior to and following the 4-week EECP program, coronary flow reserve (CFR) was recorded using transthoracic Doppler echocardiography. The serum endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) contents were analyzed by ELISA. Quality of life (QoL) was assessed by the Seattle Angina Questionnaire (SAQ) and the Canadian Cardiovascular Society (CCS) angina class. After four weeks, CFR was substantially enhanced in the EECP versus control cohort (p<0.05). Endothelin-1 was strongly diminished whereas eNOS was considerably upregulated in the EECP cohort. EECP also enhanced patients' SAQ scores and decreased the CCS angina class. Enhanced external counterpulsation may improve CFR and enhance the CMD patient QoL.

Development, validation, and comparative analysis of a simple clinical and laboratory-based risk score system for predicting and stratifying moderate-to-severe AKI after cardiac surgery

Abstract Background Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) is prevalent and detrimental following cardiac surgery, without effective prevention. Early prediction and stratification are critical in informing appropriate care. Recent studies highlighted the predictive value of some routine laboratory markers in addition to traditional clinical variables. However, existing models suffer from complexity and practical difficulties in implementation. Purpose We aim to develop a high-performance preoperative risk score system for predicting moderate-to-severe CSA-AKI, while preserving its simplicity and utility through the integration of the most predictive and routinely accessible clinical and laboratory variables. Methods A total of 14 303 patients undergoing coronary artery bypass grafting surgery at a single institution, with comprehensive perioperative data, were included. Cohort 1 (N=9 416, 2013-2017) and cohort 2 (N=4 887, 2018-2019) were used to develop and validate a risk score system for predicting moderate-to-severe CSA-AKI, respectively, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Bootstrapped stepwise regression was employed to select the robust candidate variables for a logistic regression model (i.e., the full model), which was then simplified to a more parsimonious model. Model performance was evaluated and compared to several established models. Results The overall incidence of moderate-to-severe CSA-AKI was 3.5% in the entire cohort. Two preoperative risk scores were developed: the simple 6-variable ABC2-Surgery2 score (age, a biomarker of NT-proBNP, two clinical status variables of hypertension and preoperative critical state, and two surgery-related variables of combined surgery and on-pump surgery), and the complete 10-variable AB2C3-Surgery4 score (ABC2-Surgery2 plus an additional biomarker of blood urea nitrogen, a clinical status variable of Canadian Cardiovascular Society angina class, and two surgery-related variables of urgent surgery and previous surgery). In the validation cohort, the simple score (area under the curve, AUC 0.765) outperformed the previously established UK-AKI model (AUC 0.720), Mehta score (AUC 0.700), and Ng score (AUC 0.697), while statistically similar to the most complex 19-variable Cleveland Clinic Score (AUC 0.725). The complete score (AUC 0.777) was superior to all four models. The current score system also effectively stratified CSA-AKI with respect to requirements for vasoactive support (measured by cumulative vasoactive-inotropic score), intravenous diuretics, and renal replacement therapy, as well as in-hospital and long-term mortality. Conclusion A simple risk score system incorporating routine clinical and laboratory variables was developed to predict and stratify moderate-to-severe CSA-AKI and outperformed previous complex models. Further external validation is currently underway for generalizability.

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.

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.

Improving the Data Quality of Untargeted Metabolomics through a Targeted Data-Dependent Acquisition Based on an Inclusion List of Differential and Preidentified Ions.

Metabolomics based on high-resolution mass spectrometry has become a powerful technique in biomedical research. The development of various analytical tools and online libraries has promoted the identification of biomarkers. However, how to make mass spectrometry collect more data information is an important but underestimated research topic. Herein, we combined full-scan and data-dependent acquisition (DDA) modes to develop a new targeted DDA based on the inclusion list of differential and preidentified ions (dpDDA). In this workflow, the MS1 datasets for statistical analysis and metabolite preidentification were first obtained using full-scan, and then, the MS/MS datasets for metabolite identification were obtained using targeted DDA of quality control samples based on the inclusion list. Compared with the current methods (DDA, data-independent acquisition, targeted DDA with time-staggered precursor ion list, and iterative exclusion DDA), dpDDA showed better stability, higher characteristic ion coverage, higher differential metabolites' MS/MS coverage, and higher quality MS/MS spectra. Moreover, the same trend was verified in the analysis of large-scale clinical samples. More surprisingly, dpDDA can distinguish patients with different severities of coronary heart disease (CHD) based on the Canadian Cardiovascular Society angina classification, which we cannot distinguish through conventional metabolomics data collection. Finally, dpDDA was employed to differentiate CHD from healthy control, and targeted metabolomics confirmed that dpDDA could identify a more complete metabolic pathway network. At the same time, four unreported potential CHD biomarkers were identified, and the area under the receiver operating characteristic curve was greater than 0.85. These results showed that dpDDA would expand the discovery of biomarkers based on metabolomics, more comprehensively explore the key metabolites and their association with diseases, and promote the development of precision medicine.

The effect of external counterpulsation on angiopoietin-1 and angiopoietin-2 levels in nondiabetic patients with refractory angina

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Health Research and Development of the Ministry of Health of Indonesia. Background External counterpulsation (ECP) is a noninvasive therapy that employs external compression on the lower extremities to augment coronary perfusion pressure. Numerous studies reported that ECP possesses potential benefits in enhancing the angiogenesis process by promoting expressions of several growth factors. Nondiabetic patients are believed to be more reliable in portraying the angiogenesis process. Unfortunately, the effect of ECP on angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) as angiogenesis markers has not been elucidated. Purpose The objective of this study is to evaluate the effect of ECP on Ang-1 and Ang-2 levels in nondiabetic patients with refractory angina. Methods This is a randomised, double-blind, sham-controlled clinical trial. Nondiabetic patients with refractory angina, who were not contraindicated to ECP therapy, were enrolled and randomised into ECP or sham groups. The treatment consisted of optimal medical therapy plus 35 sessions of ECP or sham, with an hour duration for each session. The pressure applied was up to 300 mmHg in the ECP group, while only 75 mmHg in the sham group. Subjective symptoms, laboratory, echocardiographic, and functional capacity parameters were measured before and after 35 sessions of treatment. Appropriate statistical tests were performed and a p-value of &amp;lt;0.05 was considered statistically significant. Results A total of 26 nondiabetic patients with refractory angina were enrolled and randomised into ECP (n=11) and sham (n=15) groups. All patients successfully followed every treatment session until the 35th session. The baseline characteristics were comparable between the two groups (p&amp;gt;0.05). After 35 sessions, there were increases in Ang-1 median levels in both ECP (1663.4 pg/ml versus 891.6 pg/ml, p=0.477) and sham groups (1577.0 pg/ml versus 1295.0 pg/ml, p=0.496). The Ang-2 median levels after the treatments were slightly lower in ECP (2849.5 pg/ml versus 2902.3 pg/ml, p=0.594), while higher in sham groups (2728.3 pg/ml versus 2376.2 pg/ml, p=0.826). Meanwhile, the ECP group also showed an improvement in the Canadian Cardiovascular Society (CCS) angina class from class III to class I/II in 18% (2 out of 11) patients, while in the sham group only 13% (2 out of 15) patients. Interestingly, the ECP group seemed to elicit a noticeable increase in Ang-1 median levels and a decrease in Ang-2 median levels. However, the effects of ECP shown in this study were not statistically significant (p&amp;gt;0.05). Conclusion The ECP group exhibited a higher trend of increase in Ang-1 level compared to the sham group. The Ang-2 level was slightly lowered in the ECP group, while increased in the sham group. Although it was not statistically significant, the increasing trend in the Ang-1 level may provide an additional understanding of the ECP angiogenic effects. Therefore, further studies to validate these results are warranted.

Proangiogenic Growth Factor Therapy for the Treatment of Refractory Angina: A Meta-analysis

<h2>Abstract</h2><h3>Background</h3> Refractory angina (RFA; limiting angina despite optimal medical therapy) is a growing, global problem, with limited treatment options. Therefore, we conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effect of proangiogenic growth factor therapy (in the form of vascular growth factors delivered either as recombinant proteins or gene therapy) in patients with RFA ineligible for revascularization. <h3>Methods</h3> We performed a meta-analysis (PROSPERO: CRD42018107283) of RCTs as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. A comprehensive search of the PubMed, CENTRAL, Embase, Cochrane, ClinicalTrials.gov and Google Scholar databases, as well as scientific session abstracts, were performed. The pooled outcomes included major adverse cardiac events (MACE), mortality, myocardial perfusion, and indices of angina severity (Canadian Cardiovascular Society angina class [CCS] and exercise tolerance). A prespecified subgroup analysis was performed for delivery method, vector, and protein type. The standardized mean difference (SMD) or odds ratio (OR) was calculated to assess relevant outcomes. We assessed heterogeneity using the χ² and I² tests. <h3>Results</h3> We included 16 RCTs involving 1607 patients (1052 received proangiogenic growth factor therapy and 555 received a placebo or optimal medical therapy). Our analysis showed a significant decreased risk of MACE (OR, 0.72; 95% confidence interval [CI], 0.55-0.93) and significantly improved CCS class (SMD, −0.55; 95% CI, −1.10 to 0.00), but not mortality (OR, 0.66; 95% CI, 0.28-1.54) or exercise tolerance (SMD, 0.47; 95% CI, −0.14 to 1.09), in treated patients compared to those in the control group. <h3>Conclusions</h3> Proangiogenic growth factor therapy is a promising treatment option for RFA, with beneficial effects seen on MACE and CCS class. The results of ongoing trials are needed before it can be considered for clinical practice.

Therapeutic Neovascularization for Refractory Angina-Are We Any Closer?

Therapeutic Neovascularization for Refractory Angina-Are We Any Closer?

A Systematic Review of CD34+ Stem Cell Therapy as an Innovative and Efficient Treatment for the Management of Refractory Angina.

Despite optimal medical treatment, many individuals suffering from severe coronary artery disease are not suitable candidates for further revascularization. Therapeutic angiogenesis has attracted continuous interest to increase myocardial perfusion. Cell therapy using autologous stem cells expressing Cluster of Differentiation 34 plus (CD34+) offers a special therapeutic choice for individuals with refractory angina, seeing as CD34+ stem cells can restore microcirculation. We searched PubMed, PubMed Central (PMC), and Google Scholar to find the relevant articles to write this systematic review about the role of CD34+ stem cell therapy in the management of refractory angina. Additionally, we provided a brief explanation of CD34+ cells and their mechanism of action. Along with the positive finding of other trials, a recent open-label, single-center intracoronary CD34+ cell therapy for the treatment of coronary endothelial dysfunction in patients with angina and nonobstructive coronary arteries (IMPROvE-CED) clinical trial published in 2022 concluded improvement in coronary blood flow, a significant reduction in daily as-needed sublingual nitroglycerin use and improvement in Canadian Cardiovascular Society (CCS) angina class were observed after autologous CD34+ cell treatment. In conclusion, refractory angina management and overall prognosis may be revolutionized once this treatment is approved.

Growth factor for therapeutic angiogenesis in ischemic heart disease: A meta-analysis of randomized controlled trials.

Aim: This study was designed to systematically evaluate the effects of growth factor (GF) for therapeutic angiogenesis on ischemic heart disease (IHD) by pooling the results of randomized controlled trials (RCTs). Methods and Results: PubMed, EMBASE, and CENTRAL databases were searched from inception to October 2022. RCTs, investigating the effects of GF therapy on IHD, were included. The risk bias of included study was assessed according to Cochrane tool. Weighted mean difference (WMD), calculated with fixed effect model or random effect model, was used to evaluate the effects of GF therapy on left ventricular ejection fraction (LVEF) and Canadian Cardiovascular Society (CCS) angina class. Relative risk (RR) was used to evaluate the effects of GF therapy on all-cause mortality, major adverse cardiovascular events (MACE) and revascularization. Meta-analysis, meta-regression analysis and publication bias analysis were performed by RevMan 5.3 or Stata 15.1 software. Twenty-nine studies involving 2899 IHD patients (1,577 patients in GF group and 1,322 patients in control group) were included. Compared with the control group, GF therapy did not reduce all-cause mortality (RR: 0.82; 95% CI: 0.54-1.24; p = 0.341), MACE [(RR: 0.83; 95% CI: 0.61-1.12; p = 0.227), revascularization (RR: 1.27, 95% CI: 0.82-1.96, p = 0.290) and CCS angina class (WMD: -0.08, 95% CI: -0.36 to 0.20, p = 0.560). However, GF therapy could increase LVEF during short-term follow-up (<1year). Conclusion: GF for therapeutic angiogenesis was beneficial for increasing LVEF during short-term follow-up (<1year), however, the therapy was not efficacious in decreasing all-cause mortality, MACE and revascularization.

Real-world data from the use of ranolazine in patients with stable angina pectoris: the RANGER study

Abstract Background Although ranolazine is available since years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on effectiveness, tolerability and safety of ranolazine are limited. Methods A non-interventional, prospective study 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. Primary endpoints comprised the weekly frequency of angina attacks, total adverse events and ranolazine discontinuation rate. 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, 1,101 patients were enrolled in 214 sites. Mean weekly angina attacks were reduced from 3.6±2.9 to 0.4±0.9 (p&amp;lt;0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7±2.2 (p&amp;lt;0.0001). CCS class and QoL were also improved (p&amp;lt;0.0001). Adverse events were reported by 11 (1%) patients totally, while 2 of them (0.2%) were characterized as serious. Treatment was discontinued for any reason 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. Conclusion Ranolazine was well-tolerated and effectively reduced angina attacks with simultaneous improvement of CCS class and QoL score in patients with stable angina. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The study was sponsored by Menarini Hellas. The study sponsor was involved in the study concept and design and in the interpretation of the data included in this publication, but not in the data collection and analysis. Menarini Hellas also funded the medical writing support for this publication.

The sham effect of invasive interventions in chronic coronary syndromes: a systematic review and meta-analysis

BackgroundSome patients with chronic coronary syndromes undergo invasive procedures but the efficacy of such interventions remains to be robustly established by randomised sham-controlled trials (RCTs).PurposeTo determine the sham effect in patients with chronic coronary syndromes enrolled in RCTs by performing a systematic review and meta-analysis.MethodsIn April 2022, we performed a literature search for published patient-blind RCTs (CENTRAL, MEDLINE®, PsycINFO, and reference lists) with sham procedures, reporting the pre-post effects in the invasive sham arm among patients with Canadian cardiovascular society (CCS) angina or angina equivalents.Results16 RCTs were included with 546 patients in the sham arm. Pooled results showed that sham interventions were associated with: improvement of 7% (95% CI 2–11%; I2 = 0%) in exercise time; decrease of 0.78 (95% CI − 1.10 to − 0.47; I2 = 75%) in CCS angina class; decrease of 53% (95% CI 24–71%; I2 = 96%) and 25% (95% CI 20–29%; I2 = 0%) in anginal episodes and nitroglycerine (NTG) use, respectively. Pooled results also showed an improvement in the physical functioning, angina frequency, treatment satisfaction, and disease perception domains of the Seattle Angina Questionnaire (SAQ).ConclusionSham interventions in patients with chronic coronary syndromes were associated with a significant decrease in anginal episodes, NTG use, and CCS angina class and increased SAQ quality of life and exercise time. These results highlight the need for previous non sham-controlled trials to be interpreted with caution, and the importance of new invasive interventions to be evaluated versus a sham procedure.

Efficacy of INtensive Treatment vs. Standard Treatment of COmpound DanshEn Dripping Pills in Refractory Angina Patients With Incomplete Revascularization (INCODER Study): Study Protocol for a Multicenter, Double-Blind, Randomized Controlled, Superiority Trial.

IntroductionPatients with incomplete revascularization (ICR) tend to develop refractory angina despite optimal medical therapy. The Compound Danshen Dripping Pills (CDDP) is a widely used antianginal drug in China and is shown to significantly alleviate myocardial ischemia. Previous studies showed dose-efficacy tendency when increasing doses of CDDP. This study aims to investigate the efficacy and safety of intensive doses of CDDP in patients with refractory angina with ICR.Methods and AnalysisThe INCODER study is a multicenter, double-blind, randomized controlled, superiority trial. We plan to recruit 250 patients aged 18–85 years with a diagnosis of refractory angina with ICR. Patients will be randomized (1:1) to intensive treatment group (CDDP 20 pills three times per day) or standard treatment group (10 pills CDDP and 10 pills placebo three times per day). Patients will have a 6-week medication period and be followed up every 2 weeks. The primary endpoint is the change of total exercise time from baseline to week 6 as assessed by cardiopulmonary exercise testing (CPET). Secondary endpoints include changes in the frequency of angina, Canadian Cardiovascular Society angina class, nitroglycerin use, Seattle Angina Questionnaire scores, peak oxygen uptake (VO2 peak) and other parameters as measured by CPET, and the levels of plasma C-reactive protein, homocysteine, and N-terminal pro-B-type natriuretic peptide. Safety events related to CDDP use will be monitored.Ethics and DisseminationThe research had been approved by the Clinical research and laboratory animal ethics committee of the First Affiliated Hospital, Sun Yat-sen University ([2019]65). The results will be reported through peer-reviewed journals, seminars, and conference presentations.Trial Registration Numberwww.chictr.org.cn (ChiCTR2000032384). Registered on 27 April 2020.

Ten-Year Outcomes of Off-Pump vs On-Pump Coronary Artery Bypass Grafting in the Department of Veterans Affairs

The long-term benefits of off-pump ("beating heart") vs on-pump coronary artery bypass grafting (CABG) remain controversial. To evaluate the 10-year outcomes and costs of off-pump vs on-pump CABG in the Department of Veterans Affairs (VA) Randomized On/Off Bypass (ROOBY) trial. From February 27, 2002, to May 7, 2007, 2203 veterans in the ROOBY trial were randomly assigned to off-pump or on-pump CABG procedures at 18 participating VA medical centers. Per protocol, the veterans were observed for 10 years; the 10-year, post-CABG clinical outcomes and costs were assessed via centralized abstraction of electronic medical records combined with merges to VA and non-VA databases. With the use of an intention-to-treat approach, analyses were performed from May 7, 2017, to December 9, 2021. On-pump and off-pump CABG procedures. The 10-year coprimary end points included all-cause death and a composite end point identifying patients who had died or had undergone subsequent revascularization (ie, percutaneous coronary intervention [PCI] or repeated CABG); these 2 end points were measured dichotomously and as time-to-event variables (ie, time to death and time to composite end points). Secondary 10-year end points included PCIs, repeated CABG procedures, changes in cardiac symptoms, and 2018-adjusted VA estimated costs. Changes from baseline to 10 years in post-CABG, clinically relevant cardiac symptoms were evaluated for New York Heart Association functional class, Canadian Cardiovascular Society angina class, and atrial fibrillation. Outcome differences were adjudicated by an end points committee. Given that pre-CABG risks were balanced, the protocol-driven primary and secondary hypotheses directly compared 10-year treatment-related effects. A total of 1104 patients (1097 men [99.4%]; mean [SD] age, 63.0 [8.5] years) were enrolled in the off-pump group, and 1099 patients (1092 men [99.5%]; mean [SD] age, 62.5 [8.5] years) were enrolled in the on-pump group. The 10-year death rates were 34.2% (n = 378) for the off-pump group and 31.1% (n = 342) for the on-pump group (relative risk, 1.05; 95% CI, 0.99-1.11; P = .12). The median time to composite end point for the off-pump group (4.6 years; IQR, 1.4-7.5 years) was approximately 4.3 months shorter than that for the on-pump group (5.0 years; IQR, 1.8-7.9 years; P = .03). No significant 10-year treatment-related differences were documented for any other primary or secondary end points. After the removal of conversions, sensitivity analyses reconfirmed these findings. No off-pump CABG advantages were found for 10-year death or revascularization end points; the time to composite end point was lower in the off-pump group than in the on-pump group. For veterans, in the absence of on-pump contraindications, a case cannot be made for supplanting the traditional on-pump CABG technique with an off-pump approach. ClinicalTrials.gov Identifier: NCT01924442.

Patients’ perception of health status and ischaemic burden in stable coronary artery disease

Background: Angina pectoris, the main manifestation of coronary artery disease has an unfavorable impact on quality of life. The aim of this study was to assess Health-Related Quality Of Life (HRQoL) in patients with Stable Coronary Artery Disease (SCAD) and to explore possible relationships between HRQoL and the risk factors for ischaemic heart disease, the Canadian Cardiovascular Society (CCS) angina severity class, and the extent of myocardial ischaemia on Single Photon Emission Computed Tomography Myocardial Perfusion Imaging (SPECT-MPI). Methods: HRQoL was assessed with the use of two generic questionnaires, EQ-5D-3L and SF-36v2 in one hundred consecutive patients with SCAD. Results: Most of the patients presented problems on the dimensions of mobility, pain/discomfort, and anxiety/depression of the EQ5D questionnaire. The EQ-VAS score was 61.96 ± 20.99, and the mean EQ-5D index value was 0.54 ± 0.31. The mean scores of the Physical Component Summary and the Mental Component Summary of the SF-36 questionnaire were 43.49 and 41.01 respectively. Higher CCS angina class, female gender and poor physical activity were significantly correlated with worse HRQoL. No statistically significant association was detected between HRQoL and the extent of ischaemia on myocardial perfusion imaging. Conclusions: Patients with SCAD have an impaired HRQoL, which can be reliably assessed by generic HRQoL questionnaires. Angina severity could be used as a surrogate of HRQoL, but individual perception of health status should be measured independently of the amount of ischaemiaon cardiac perfusion scintigraphy Keywords: health related quality of life; myocardial perfusion imaging; coronary artery disease.

The Placebo Effect on Symptoms, Quality of Life, and Functional Outcomes in Patients With Angina Pectoris: A Meta-analysis of Randomized Placebo-Controlled Trials.

The placebo effect is a well described phenomenon in blinded studies evaluating antianginal therapeutics, although its effect on clinical research metrics remains unknown. We conducted a systematic review and meta-analysis to quantify the effect of placebo on end points of symptoms, life quality, and functional outcomes in randomized placebo-controlled trials (RCTs) of symptomatic stable coronary artery disease. We systematically reviewed MEDLINE, EMBASE, and the Cochrane database for double-blind RCTs of antiangina therapeutics. Patients randomized to the placebo arm were the study population. Main outcomes were the changes in exercise performance (exercise treadmill test [ETT] parameters), quality of life (Seattle Angina Questionnaire domains), symptoms (Canadian Cardiovascular Society angina class) and drug usage (nitroglycerin tablets per week) between baseline and after placebo treatment. The primary outcome was ETT total duration time. Data were pooled with a random effect model. Seventy-eight RCTs (83% drug-controlled, 17% procedure-controlled) were included encompassing 4925 patients randomized to placebo. ETT total duration time was significantly improved after placebo treatment compared with baseline (mean, 29.2; 95% confidence interval, 20.6-37.8] seconds) with evidence of high heterogeneity (I2 = 98%) At subgroup analysis, crossover design was associated with a smaller placebo effect on ETT performance than parallel study design (P for interaction = 0.001). A significant placebo effect was observed for all secondary outcomes with overall high heterogeneity. A substantial placebo effect was present in angina RCTs across a variety of functional and life quality metrics. High variability in placebo effect size was present, mostly unexplained by differences in study and patient characteristics.

Randomized Trial of Metoprolol in Patients With Obstructive Hypertrophic Cardiomyopathy

BackgroundThe use of β-adrenergic receptor blocking agents in symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM) rests on clinical experience and observational cohort studies. ObjectivesThis study aimed to investigate the effects of metoprolol on left ventricular outflow tract (LVOT) obstruction, symptoms, and exercise capacity in patients with obstructive HCM. MethodsThis double-blind, placebo-controlled, randomized crossover trial enrolled 29 patients with obstructive HCM and New York Heart Association (NYHA) functional class II or higher symptoms from May 2018 to September 2020. Patients received metoprolol or placebo for 2 consecutive 2-week periods in random order. The effect parameters were LVOT gradients, NYHA functional class, Canadian Cardiovascular Society (CCS) angina class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and cardiopulmonary exercise testing. ResultsCompared with placebo, the LVOT gradient during metoprolol was lower at rest (25 mm Hg [interquartile range (IQR): 15-58 mm Hg] vs 72 mm Hg [IQR: 28-87 mm Hg]; P = 0.007), at peak exercise (28 mm Hg [IQR: 18-40 mm Hg] vs 62 mm Hg [IQR: 31-113 mm Hg]; P < 0.001), and postexercise (45 mm Hg [IQR: 24-100 mm Hg] vs 115 mm Hg [IQR: 55-171 mm Hg]; P < 0.0001). During metoprolol treatment, 14% of patients were in NYHA functional class III or higher compared with 38% of patients receiving placebo (P < 0.01). Similarly, no patients were in CCS class III or higher during metoprolol treatment compared with 10% during placebo treatment (P < 0.01). These findings were confirmed by higher KCCQ-OSS during metoprolol treatment (76.2 ± 16.2 vs 73.8 ± 19.5; P = 0.039). Measures of exercise capacity, peak oxygen consumption, and N-terminal pro–B-type natriuretic peptide did not differ between the study arms. ConclusionsCompared with placebo, metoprolol reduced LVOT obstruction at rest and during exercise, provided symptom relief, and improved quality of life in patients with obstructive HCM. Maximum exercise capacity remained unchanged. (The Effect of Metoprolol in Patients with Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802)

Original Article--Value of Pathological Q Waves and Angiographic Collateral Grade in Patients Undergoing Coronary Chronic Total Occlusion Recanalization: Cardiac Magnetic Resonance Study.

Background/aimSuccessful coronary chronic total occlusion (CTO) revascularization was found by many studies to be associated with improved left ventricular (LV) systolic function and survival if evidence of viability is present. Little is known about the association of CTO revascularization in patients with electrocardiographic Q waves and improvement in angina burden as a measurement of health-related quality of life (HRQOL) afterwards.MethodsIn this study, 100 patients with single vessel CTO were included. Myocardial viability was tested by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) and 50 patients showed evidence of viability. Seattle Angina Questionnaire (SAQ) scores were used as a measure of HRQOL.ResultsPathological Q waves were present in 48 patients (including 19 patients with viable CTO territory) out of 100 patients. Patients with Q waves tended to have worse Seattle Angina Questionnaire (SAQ) scores compared to those with no Q waves (31.2 ± 11.7 vs 45.3 ± 13.9 respectively, p = 0.002), worse LV systolic function and wall motion score index (WMSI) on CMR. They also had significantly less prevalence of viability (p < 0.001). Patients with Q waves and positive viability had lower SAQ scores (37.2 ± 10.1 vs 52.7 ± 13.2 respectively, p = 0.02), higher LVEF and lower WMSI. They also had well developed collateral grade (2.1 ± 1.03 vs 0.7 ± 0.82 respectively, p < 0.001). After successful percutaneous coronary intervention (PCI), in the viable LV group, presence of Q waves was not associated with better LV functional recovery, while those with higher collateral grades were more likely to have better LV functional recovery post CTO-PCI. Patients with Q waves and viable CTO territory showed significantly better SAQ scores compared to pre-PCI (87.3 ± 12.2 vs 37.2 ± 10.1 respectively, p < 0.001). For angina frequency, post–PCI score was 80.2 ± 7.9 compared to 39.2 ± 7.1 before PCI, p < 0.001). Multivariate regression analysis showed that pathological Q waves, Rentrop's collateral grade and the Canadian Cardiovascular Society (CCS) angina class before PCI were the most significant independent predictors of improved HRQOL as reflected by SAQ (OR for Q waves 7.83, 95% CI 1.62–18.91,p 0.003), (OR for Rentrop's collateral grade 8.31,95% CI 2.21–26.33, p < 0.001), (OR for CCS class 8.39, 95% CI 1.21–20.8, p 0.01).ConclusionWell-developed collateral circulation could independently predict LV functional recovery after CTO-PCI. Patients with Q waves and viable CTO territory tend to have higher CCS class before revascularization and get significant improvement of HRQOL after PCI. Other predictors of improved HRQOL are Rentrop's collateral grade and worse CCS class before PCI.

Abstract 13124: Exercise Capacity as a Predictor of the Placebo-controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Ventilatory Gas Exchange-stratified Analysis of ORBITA

Introduction: Improvement in exercise capacity is a therapeutic goal of percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD). Cardiopulmonary exercise testing (CPET) provides an accurate quantification of cardio-respiratory fitness through analysis of ventilatory gas exchange (VGE). The aim of this secondary analysis from the ORBITA trial is to determine the placebo-controlled effect of PCI on VGE parameters and determine if pre-randomisation exercise capacity predicts the placebo-controlled efficacy of PCI. Methods: Following a 6-week medication optimisation phase, patients with severe single vessel CAD underwent pre-randomisation treadmill CPET using the smoothed modified Bruce protocol. Patients were then randomly assigned to PCI or a placebo procedure. At the end of the 6-week follow up period, patients underwent repeat CPET before being unblinded to treatment allocation. Results: CPET data was available for 195 patients (mean age 66.1 ± 9.1, 73.3% male). At baseline, peak oxygen uptake (VO 2 ) was 21.5±6.7ml/kg/min in the PCI arm (n=102) and 20.6±6.6ml/kg/min in the placebo arm (n=93). At follow up, there was no significant benefit from PCI over a placebo procedure for any ventilatory gas exchange (peak VO 2 , p=0.826; O 2 -pulse plateau, p=0.638) or haemodynamic parameter (rate-pressure product, p=0.215). Although PCI resulted in significantly improved patient-reported freedom from angina (OR, 2.58 [95% CI, 1.35-14.92] p=0.004) and angina frequency score (OR, 1.73 [95% CI, 1.02 to 2.96], p=0.0432), there was no detectable interaction between peak VO 2 and these endpoints (P interaction(int) =0.715 and P int =0.588 respectively). Similarly, pre-randomisation peak VO 2 did not predict the placebo-controlled benefit of PCI on physical limitation (P int =0.293), quality of life (P int =0.380), EuroQOL 5 visual analogue score (P int =0.695), Canadian Cardiovascular Society angina class (P int =0.120) or exercise time (P int =0.897). Conclusions: When assessed against placebo, PCI does not improve VGE or exercise capacity, assessed by CPET. Furthermore, pre-randomisation exercise capacity does not predict the placebo-controlled effect of PCI on symptom relief, even in patients with lower functional capacity.