Canadian Cardiovascular Society Angina Class Research Articles

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.

Abstract 16998: Gender and Age Specific Baseline Predictors of MACE in PEACE Trial Identified by Machine Learning

Introduction: The NHLBI supported Prevention of Events with Angiotensin-Converting Enzyme (ACE) Therapy trial (PEACE) (NCT00000558) found that the addition of ACE inhibitor trandolapril to conventional therapy in 8290 patients with stable coronary artery disease and preserved ejection fraction provided no benefit against MACE (cardiovascular death, nonfatal myocardial infarction, or the need for coronary revascularization), the composite primary endpoint. We reused publicly available individual patient-level PEACE data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) using random survival forest (RSF) to identify gender and age group specific predictors for MACE. Methods: RSF was performed on 50 baseline variables for the MACE outcome in male and female and in age group (&lt;60, 60-69, &gt;69) cohorts. The top ten predictors identified in each cohort were included in a multivariate analysis using a Cox proportional hazards model with a multiple regression approach. Results: The top 10 predictors for the MACE selected by RSF are shown in Figure 1. Expected cardiovascular (CV) risk predictors like blood pressure, Canadian CV Society angina classification (CCS), age, and a history of various CV procedures consistently emerge amongst the top ten predictors of the primary MACE outcome across all gender and age specific subgroups. Interestingly, RSF also identified renal function biomarkers like serum potassium and glomerular filtration rate as common top ten predictors. Conclusion: Using ML, we uncovered in an unbiased fashion, gender and age groups specific unanticipated top predictors for MACE in PEACE trial. This underscores the value of gender and age specific predictors to examine the efficacy and outcomes of therapeutic interventions in advancing precision and personalized medicine.

Abstract 13116: Ventilatory Gas Exchange in Stable Coronary Artery Disease

Introduction: Cardiopulmonary exercise testing (CPET) provides a non-invasive evaluation of exercise physiology via ventilatory gas exchange (VGE). We do not know how these assessments correlate with myocardial ischemia or angina symptoms in patients with stable single-vessel coronary artery disease (CAD). In this analysis, we use randomised, blinded data from the ORBITA trial to investigate the association between VGE, ischemia and symptoms in patients with severe single-vessel CAD. Methods: Patients underwent treadmill CPET using the smoothed-modified Bruce protocol, after a 6-week medical optimisation phase during which antianginals were uptitrated. Symptoms were assessed using the Seattle Angina Questionnaire (SAQ), EuroQOL 5 and Canadian Cardiovascular Society (CCS) angina class. Ischemia was quantified using fractional flow reserve (FFR), instantaneous wave-free ratio (iFR) and dobutamine stress echocardiography (DSE). Results: We assessed 195 patients [mean age 66.1±9.1, 143 (73.3%) male]. We found a significant association between peak oxygen uptake (VO 2 ) and minute ventilation to carbon dioxide (VE/VCO 2 ) slope, and physician assessed CCS class [P correlation(cor) &lt;0.0001(Figure 1), P cor &lt;0.0001, respectively], patient-reported SAQ angina frequency score [P cor &lt;0.011(Figure 1), P cor &lt;0.0001], physical limitation (P cor &lt;0.0001, P cor =0.0001) and EuroQOL 5 visual analogue score (P cor = 0.0011, P cor =0.0019). There was no detectable relationship between peak VO 2 or VE/VCO 2 slope, and FFR, iFR or DSE (p&gt;0.05, for all). Patients with an oxygen pulse plateau however, had higher dobutamine stress echo score compared to those without (+0.71; 95%CI 0.22-1.21, p=0.0049). Conclusions: The association between VGE and angina symptoms is stronger than its ability to detect severity of myocardial ischemia. This analysis highlights the complexity of the relationship between symptoms, functional capacity and myocardial ischemia.

Ranolazine in refractory and chronic stable angina

Aim/Objectives: The current Scottish Intercollegiate Guidelines Network (SIGN) guidelines recommend beta blockers and dihydropiridine calcium channel blockers as first-line agents for refractory angina pectoris. Despite being optimally treated with pharmacotherapy and revascularisation, up to 40% of patients still experience symptoms. Ranolazine, a piperazine derivative, selectively inhibits late sodium currents and is of particular interest as it is currently not recommended routinely by SIGN guidelines and Scottish Medicine Consortium (SMC) but has been prescribed in Tayside, initially through IPTR since 2017 and recently through a Local New Medicine Treatment Protocol and Stable Angina Pathway. Real world experience of ranolazine prescribing in patients with chronic and often refractory angina is not widely reported. We therefore audited its use in Tayside to understand its prescribing pattern within our patient population and assess its effects on angina symptom relief. Methods: Electronic health records and prescribing data between 1st January 2012 and 31st December 2018 were retrospectively analysed. Data on baseline characteristics, prescribing information, past medical history, and angina symptom control were collected. Standard descriptive statistics were used for analysis. Results: 35 patients were identified as suitable for inclusion in the audit. Mean age was 71.4 ± 12.5 years old and 68.6% were male. 23 patients (65.7%) had either a previous percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). The most common reason for ranolazine prescription was refractory angina (74.3%) with 375 mg BD being the most common dose. Prescription of guideline-recommended anti anginals was high with 80% of patients being on a beta blocker and a nitrate prior to commencing ranolazine. Encouragingly, 27 patients (77.1%) reported an improvement in Canadian Cardiovascular Society (CCS) angina class and the rate of non-responders was 22.9%. No adverse effects leading to discontinuation of ranolazine was found. Conclusion: Ranolazine may play a role as an additional anti anginal agent with reasonable achievement of symptom control in patients who have refractory angina despite the use of other guideline-recommended anti anginal agents.

Impact of extracorporeal shockwave myocardial revascularization on the ischemic burden of refractory angina patients: a single photon emission computed tomography study.

Extracorporeal shockwave myocardial revascularization (ESMR) is a non-invasive treatment designed to improve symptoms in refractory angina (RA) patients. Enhanced perfusion through local vasodilation and neo-capillarization is postulated to be the mechanism of the observed clinical benefit. However, the impact of ESMR on the ischemic burden of RA patients has not been adequately assessed. One-hundred twenty-one consecutive RA patients suitable for ESMR were treated. Twenty-nine RA patients not suitable for treatment were clinically followed-up as a control group for clinical endpoints. ESMR-treated patients underwent baseline and 6-month single photon emission computed tomography (SPECT) to evaluate the changes in ischemic burden. The operator was blinded to the pre/post-treatment status of the SPECT exam. The primary endpoint was the difference in summed stress score (SSS) and summed difference score (SDS) between follow-up and baseline SPECTs. Secondary endpoints included the changes in Canadian Cardiovascular Society (CCS) angina class and nitroglycerin use between 6-month follow-up and baseline. Clinical endpoints were further compared between ESMR-treated patients and the control group. Following ESMR, a significant reduction in the ischemic burden was observed (follow-up SSS: 14.2±10 vs. baseline SSS: 21.2±9.42, P<0.0001; follow-up SDS: 4.6±5.9 vs. baseline SDS 10.2±7.9, P<0.0001) including less patients with moderate to severe ischemia (19% vs. 46% P<0.0001). CCS class and nitroglycerin use were significantly reduced (CCS: 1.5±0.6 vs. 2.7±0.6, P<0.0001; patients needing nitroglycerin: 24% vs. 64%, P<0.0001). When compared to the control group, CCS class reduction, nitroglycerin use and hospitalizations were significantly lower for ESMR treated vs. non-treated RA patients at 6-month follow-up. In this single-center cohort of RA patients undergoing ESMR treatment and serial myocardial perfusion imaging, ESMR was associated with a significant reduction in the ischemic burden. These findings provide a physiological rationale and mechanism for the observed clinical benefit.

The Coronary ARteriogenesis with combined Heparin and EXercise therapy in chronic refractory Angina (CARHEXA) trial: A double-blind, randomized, placebo-controlled stress echocardiographic study.

Coronary collateral circulation exerts protective effects on myocardial ischaemia due to coronary artery disease and can be promoted by exercise with heparin co-administration. Whether this arteriogenetic effect is accompanied by functional improvement of left ventricle during stress and lessening of angina symptoms remains unknown. To evaluate the anti-ischaemic efficacy of heparin plus exercise in coronary artery disease. In a prospective, single-centre, randomized, double-blind study we recruited 32 'no-option' patients (27 males; mean age 61 ± 8 years) with stable angina, exercise-induced ischaemia and coronary artery disease not suitable for revascularization. All underwent a two-week cycle of exercise (two exercise sessions per day, five days per week) and were randomized (n = 16 per group) to intravenous placebo (0.9% saline) versus unfractionated heparin (5.000 IU intravenously), 10 min prior to exercise. We assessed Canadian Cardiovascular Society angina class, stress electrocardiogram and echo parameters (wall motion score index) and computed tomography angiography for collaterals. After two-week cycle, Canadian Cardiovascular Society class statistically decreased in both groups (heparin plus exercise group: 2.6 ± 0.7 to 1.9 ± 0.7, p < 0.001, exercise group: 2.4 ± 0.7 to 2.1 ± 0.9, p = 0.046). Only the heparin plus exercise group improved time-to-ST segment depression (before 270, 228-327 s vs. after 339, 280-360 s, p = 0.012) and wall motion score index (before 1.38 ± 0.25 vs. after 1.28 ± 0.18, p = 0.005). By multi-slice computed tomography angiography, collaterals improved in 12/15 (80%) in the heparin plus exercise group versus 2/16 (12.5%) in the exercise group (p < 0.001). A two-week, 10-test cycle of heparin plus exercise is better than exercise in improving angina class, myocardial ischaemia and collaterals by computed tomography angiography.

Dobutamine Stress Echocardiography Ischemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echocardiography-Stratified Analysis of ORBITA.

Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina). One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling. At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426). The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.

Angina pectoris severity and late-life frailty among men with cardiovascular disease

Objective We investigated the association between severity of angina pectoris (AP) and subsequent late-life frailty among men with cardiovascular disease (CVD). Method A subset of 351 men (mean age at baseline 56.7 ± 6.5 years) who previously participated in the Bezafibrate Infarction Prevention, BIP trial (1990–1997) underwent a neurovascular evaluation as part of the BIP Neurocognitive study 15.0 ± 3.0 years after baseline (T1) and a frailty evaluation according to Fried 19.9 ± 1.0 years after baseline (T2). Severity of AP was assessed at baseline of the BIP trial using the Canadian Cardiovascular Society angina classification. We assessed the odds of being in the advanced rank of frailty status (robust, pre-frail, and frail) using ordered logistic regression. Results Among 351 participants, 134 (38.2%) were classified as pre-frail and 100 (28.5%) as frail. Frailty was found among 42% participants in the AP class ≥2 and among 26% participants in the AP class <2. Adjusting for demographic, health-related and cognitive variables, odds ratio (OR), and 95% confidence interval (95% CI) for advanced rank of frailty was 2.68 (95% CI: 1.29–5.59) comparing AP class ≥2 to AP class <2. Discussion Among men with CVD, severity of AP should be taken into risk consideration due to its strong association with late-life frailty, particularly among inactive participants and participants with cerebral microvascular damage.

The Impact of Cell Therapy on Cardiovascular Outcomes in Patients With Refractory Angina.

Cell-based therapies are a novel potential treatment for refractory angina and have been found to improve markers of angina. However, the effects on mortality and major adverse cardiac events (MACE) have not been definitively investigated. To investigate the efficacy and safety of stem cell treatment compared with optimal medical treatment for refractory angina by conducting an updated meta-analysis, looking at clinical outcomes. We performed a systematic review and meta-analysis of randomized controlled trials using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A comprehensive search was performed of PubMed, EMBASE (Excerpta Medica database), Cochrane, ClinicalTrials.gov , Google Scholar databases of randomized controlled trials, and scientific session abstracts. Studies were deemed eligible if they met the following criteria: (1) full-length publications in peer-reviewed journals; (2) evaluated cell therapy use in patients with no further revascularisation options while on optimal medical treatment; (3) patients had ongoing angina, Canadian Cardiovascular Society class II-IV; and (4) included a placebo/control arm. We calculated risk ratios for all-cause mortality, combined MACE events. We assessed heterogeneity using χ2 and I2 tests. We identified 1191 citations with 8 randomized controlled trials meeting inclusion criteria involving 526 patients. Outcomes pooled were MACE, mortality, and indices of angina (angina episodes, Canadian Cardiovascular Society angina class, exercise tolerance, and antianginal medications). Our analysis showed a decreased risk of both MACE (odds ratio, 0.41; CI, 0.25-0.70) and mortality (odds ratio, 0.24; 95% CI, 0.10-0.60) in cell-treated patients compared with patients on maximal medical therapy. This was supported by improvements in surrogate end points of anginal episodes, use of antianginal medications, Canadian Cardiovascular Society class, and exercise tolerance. In addition to improvements in indices of angina, cell-based therapies improve cardiovascular outcomes (mortality/MACE) in patients with refractory angina. Given the premature termination of the phase III study, this supports the need for further definitive trials. Prospero Registration : URL: https://www.crd.york.ac.uk/prospero/ . Unique identifier: CRD42018084257.

Outcomes after transaortic transcatheter aortic valve implantation: long-term findings from the European ROUTE†.

There is lack of data regarding the longer-term outcomes of patients undergoing transaortic (TAo) transcatheter aortic valve implantation (TAVI). We aimed to provide a contemporary snapshot of the types and frequencies of events in the year following TAo-TAVI. The Registry of the Utilization of the TAo-TAVI approach using the Edwards SAPIEN Valve (ROUTE) is a multicentre, European, prospective, observational registry of aortic stenosis patients undergoing TAo-TAVI. Patients were grouped according to the composite end point death, myocardial infarction, stroke/transient ischaemic attack, major vascular complications, life-threatening bleeding, acute kidney injury (AKI) and/or cardiovascular rehospitalization. Two hundred and fifty-three patients with a mean age of 81.5 ± 5.8 years were included, of whom 89 (35.2%) patients met the composite end point (the event group) and 164 (64.8%) patients did not (the event-free group). New York Heart Association (NYHA) class III/IV (85.2% vs 71.8%, P = 0.017), Canadian Cardiovascular Society angina class III/IV (22.6% vs 11.4%; P = 0.021), pulmonary disease (32.6% vs 18.9%; P = 0.015) and renal insufficiency (15.7% vs 3.0%; P < 0.001) were more common in the event group. At 1 year, the most common event was death (19.1%), followed by AKI stage II or III (14.7%). The baseline renal insufficiency was the strongest independent predictor of composite end point achievement [odds ratio (OR) 7.55, 95% confidence interval (CI) 2.33-24.56], followed by NYHA class III/IV (OR 2.316, 95% CI 1.06-5.06) and pulmonary disease (OR 2.91, 95% CI 1.45-5.85). Pulmonary disease was also an independent predictor of 1-year mortality (OR 3.01, 95% CI 1.34-6.75). Long-term outcomes after TAo-TAVI appear to be similar to those for TAVI via other non-transfemoral access routes. Awareness of characteristics associated with poorer outcomes may aid patient selection and identification of those requiring closer post-procedural monitoring. ClinicalTrials.gov identifier: NCT01991431.

Vascular endothelial growth factor gene transfer therapy for coronary artery disease: A systematic review and meta-analysis.

It is not clear whether treatment by vascular endothelial growth factor (VEGF) gene transfer can improve myocardial ischemia through a proangiogenesis mechanism and is effective against coronary artery disease (CAD). We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared VEGF gene therapy and standard treatments in CAD. We systematically searched the PubMed, Embase, and Cochrane databases and relevant references for RCTs (published up to May 2018; no language restrictions) and performed meta-analysis using both fixed and random effects models. Our primary outcome measures were mortality and serious cardiac events. The secondary outcome measures were follow-up left ventricular ejection fraction (LVEF), change in LVEF (ΔLVEF), and angina outcomes. The registration number is CRD42017058430. Of 524 identified studies, 14 were eligible and were included in our analysis. At a mean follow-up of 6months, VEGF gene therapy demonstrated a decreased risk of serious cardiac events (11.7% vs 21.2%, relative risk: 0.56; 95% confidence interval (CI): 0.37, 0.84; P=0.005) and a slight improvement in follow-up LVEF (weighted mean difference: 1.95; 95%CI: 1.28, 2.62). Furthermore, VEGF gene therapy using adenoviral vectors showed more potential benefit in terms of the risk of serious cardiac events, ΔLVEF, and Canadian Cardiovascular Society angina class. Nevertheless, mortality and angina frequency scores were not different. Vascular endothelial growth factor gene therapy appears to be safe and effective regarding serious cardiac events, with greater benefit when using adenoviral vectors. This meta-analysis highlights the need for further exploration in these areas.

ENHANCED EXTERNAL COUNTERPULSATION EFFECTIVENESS ON CLINICAL PARAMETERS IN DIABETIC AND NON-DIABETIC CORONARY HEART DISEASE PATIENTS

Objectives: The objectives of the study were to assess the effectiveness of enhanced external counterpulsation (EECP) treatment on clinical profile comprising physiological, biochemical, and clinical symptoms of diabetic and non-diabetic coronary heart disease (CHD) patients.Methods: A pretest–posttest designed prospective study with 163 diabetic and non-diabetic CHD patients enrolled in Science and Art of Living Heart Center (SAAOL), New Delhi, India. Angina severity was assessed using Canadian Cardiovascular Society (CCS) angina classification scale and dyspnea status was assessed using medical research council (MRC) scale. The study subjects were followed up for 12 months. Statistical analysis was done using the SPSS v21 software. Descriptive analysis with sample t-test for two independent groups and paired sample t-test for EECP effectiveness within the group was done.Results: A minute difference in body mass index mean (30.1±5.86–29.9±5.62 vs. 27.5±4.17–27.16±3.88) was observed in diabetic and non-diabetic CHD patients, but that was not statistically significant. A significant drop out in blood sugar fasting (166.7±41.9–150.1±23.7), blood sugar postprandial (204.7±64.4–173.2±41.2), and glycosylated hemoglobin (7.9±0.8 to 7.5±0.6) was also observed in diabetic CHD patients from baseline to 12th month after completion of EECP treatment with significant p&lt;0.001, that may be due to EECP treatment. CCS angina classification score and MRC dyspnea score also significantly improved after EECP treatment.Conclusion: EECP treatment may improve clinical symptoms of CHD and lower the blood glucose level in diabetic CHD patients. This treatment may be effective for CHD patients with diabetes mellitus.

A comprehensive meta-analysis of stem cell therapy for chronic angina.

A substantial proportion of patients with coronary artery disease do not achieve complete revascularization and continue to experience refractory angina despite optimal medical therapy. Recently, stem cell therapy has emerged as a potential therapeutic option for these patients. However, findings of individual trials have been scrutinized because of their small sample sizes and lack of statistical power. Therefore, we conducted an updated comprehensive meta-analysis of available randomized controlled trials (RCTs) with the largest sample size ever reported on this subject. In patients with chronic angina stem cell therapy improves clinical outcomes. Scientific databases and websites were searched for RCTs. Data were independently collected by 2 investigators, and disagreements were resolved by consensus. Data from 10 trials including 658 patients were analyzed. Stem cell therapy improved Canadian Cardiovascular Society angina class (risk ratio: 1.53, 95% CI: 1.09 to 2.15, P = 0.013), exercise capacity (standardized mean difference [SMD]: 0.56, 95% CI: 0.23 to 0.88, P = 0.001), and left ventricular ejection fraction (SMD: 0.63, 95% CI: 0.27 to 1.00, P = 0.001) compared with placebo. It also decreased anginal episodes (SMD: -1.21, 95% CI: -2.40 to -0.02, P = 0.045) and myocardial perfusion defects (SMD: -0.70, 95% CI: -1.11 to -0.29, P = 0.001). However, no improvements in all-cause mortality were observed after a relatively short follow-up. In patients with chronic angina on optimal medical therapy, stem cell therapy improves symptoms, exercise capacity, and left ventricular ejection fraction. These findings warrant confirmation using larger trials.

Coronary Sinus Reducer Implantation for the Treatment of Chronic Refractory Angina: A Single-Center Experience

ObjectivesThe aim of this study was to assess the safety and efficacy of the Reducer in a real-world cohort of patients presenting with refractory angina. BackgroundThe coronary sinus Reducer is a novel device to aid in the management of patients with severe angina symptoms refractory to optimal medical therapy and not amenable to further revascularization. MethodsFifty patients with refractory angina and objective evidence of myocardial ischemia who were judged unsuitable for revascularization were treated with coronary sinus Reducer implantation at a single center between March 2015 and August 2016. Safety endpoints were procedural success and the absence of device-related adverse events. Efficacy endpoints, assessed at 4- and 12-month follow-up, were a reduction in Canadian Cardiovascular Society angina class, improvement in quality of life assessed using the Seattle Angina Questionnaire, improvement in exercise tolerance assessed using the 6-min walk test, and reduction in pharmacological antianginal therapy. ResultsProcedural success was achieved in all patients, with no device-related adverse effects during the procedure or at follow-up. Regarding the efficacy endpoint, 40 patients (80%) had at least 1 reduction in Canadian Cardiovascular Society class, and 20 patients (40%) had at least 2 class reductions, with a mean class reduction to 1.67 ± 0.83 vs. 2.98 ± 0.52 (p < 0.001) at 4-month follow-up. All Seattle Angina Questionnaire items improved significantly (p < 0.001 for all). A significant increment in 6-min walk distance to 388.6 ± 119.7 m vs. 287.0 ± 138.9 m (p = 0.004) was observed. Sixteen patients (32%) and 3 patients (6%) demonstrated reductions of at least 1 or 2 antianginal drugs, respectively. The benefit of Reducer implantation observed at 4-month follow-up was maintained at 1 year. ConclusionsIn this real-world, single-center experience, implantation of the coronary sinus Reducer appeared safe and was associated with reduction in anginal symptoms and improvement in quality of life in patients with refractory angina who were not candidates for further revascularization.

Abstract 125: Natural Language Processing Identifies an Association Between Canadian Cardiovascular Society Angina Severity and Mortality Within the Department of Veterans Affairs

Background: Stable angina is estimated to affect more than 10 million Americans and is the presenting symptom in half of patients diagnosed with coronary disease. Documentation of angina severity resides as unstructured data and is often unavailable in large datasets. We used natural language processing (NLP) to identify Canadian Cardiovascular Society (CCS) angina class and determine the association with all-cause mortality in an integrated health system’s electronic records (EHR). Methods: We performed a historic cohort study using national Veterans Health Administration data between 1/1/06 and 12/31/13. Veterans with incident stable angina were identified by ICD-9-CM codes. We developed an NLP tool to extract CCS class from free text notes. Risk ratios (RR) for all-cause mortality at one year associated with CCS class were calculated using Poisson regression. Results: There were 299,577 Veterans with angina, of which 14,216 had at least one CCS class extracted via NLP. Mean age was 66.6 years, 98% were male sex, and 82% were white. Diabetes increased with CCS class, but other comorbidities were stable (Table). There were 719 deaths at one year follow-up. The adjusted RR for all-cause mortality at one-year comparing Class III to Class I and Class IV to Class I was 1.40 (95% CI 1.16 - 1.68) and 1.52 (95% CI 1.13 - 2.04), respectively. Conclusion: NLP-derived CCS class was independently associated with one year all-cause mortality. Its application may be limited by inadequate EHR documentation of angina severity.

Outcome of coronary artery bypass graft surgery in patients with low ejection fraction

Background: Patients with low ejection fraction (EF) are at high risk for postoperative complication and mortality. Our aim was to assess the effect of low EF on clinical outcome after surgery. Objective: The present study evaluates our experience with coronary artery bypass grafting in patients with low EF. Materials and Methods: We analyzed the data of 35 patients with EF <35%. All participants were assessed preoperatively with respect to patient characteristics, risk factors, and preoperative two dimension echocardiography (2D ECHO). Depending on findings of 2D ECHO patients were divided into three groups: in Group 1, we included patients with EF 30%–35%, Group 2 comprised patients with EF of 25%–30%, and Group 3 consisted of patients with EF <25%. Patients were operated by off-pump coronary artery bypass grafting; only three patients were operated by on-pump beating heart surgery. We noted a mean number of grafts required, use of intra-aortic balloon counterpulsation (intra-aortic balloon pump) intraoperatively and postoperatively, postoperative complication, mortality, mean hospital stay, postoperative improvement in EF, and postoperative control of angina and symptomatic improvement. Results: Hospital mortality rate in present series was 11%. Mean grafts were 3.02 per patient. Fourteen (40%) patient had a postoperative complication. EF improved in 78% of patients. Canadian Cardiovascular Society Angina class improved in 42% of patients. Conclusion: In patients with coronary artery disease and low EF, CABG can be performed safely, and improvement in left ventricular function can be achieved with this procedure improving the quality of life.

TCTAP C-124 Recurrent Occlusion of Left Anterior Descending Artery During Intervention of Left Main Bifurcation

### Patient initials or identifier number STK ### Relevant clinical history and physical exam A 67-year-old man has experienced recurrent unstable angina pectoris (Canadian Cardiovascular Society angina class IV) in the last six months. He had a 30-year history of smoking twenty cigarettes per