Chronic Total Occlusions: A State-of-the-Art Review.

The percutaneous management of chronic total occlusions (CTO) is a well-established sub-specialty of Interventional Cardiology, requiring specialist equipment, training, and techniques. The heterogeneity of approaches in CTO has led to the generation of multiple algorithms to guide operators in their management. The evidence base for management of CTOs has suffered from inconsistent descriptive and quantitative terminology in defining the nature of lesions and techniques utilised, as well as seemingly contradictory data about improvement in ventricular function, symptoms of angina, and mortality from large-scale registries and randomised controlled trials. Through this review, we explore the history of CTO management and its supporting evidence in detail, with an outline of limitations of CTO-percutaneous coronary intervention and a look at the future of this growing field within cardiology.

Association of Successful Percutaneous Revascularization of Chronic Total Occlusions With Quality of Life: A Systematic Review and Meta-Analysis.

Importance: Chronic total occlusion percutaneous coronary intervention (CTO-PCI) is not usually offered because of skepticism about long-term clinical benefits. Objective: To assess the association of successful CTO-PCI with quality of life by analyzing the relevant domains of the Seattle Angina Questionnaire (SAQ). Data Sources: PubMed, EMBASE, Web of Science, Google Scholar, and Cochrane databases were searched to identify randomized trials and observational studies specifically addressing quality of life domains of SAQ from January 2010 to June 2022. Study Selection: Studies included reporting SAQ metrics such as angina frequency, physical limitation, and quality of life, before and after CTO-PCI. Data Extraction and Synthesis: The present study was performed according to the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements, in which fixed-effect or random-effect models with generic inverse-variance weighting depending on statistical homogeneity were applied. Data were extracted by 3 independent reviewers. Outcomes and Measures: The primary outcome was angina frequency; physical limitation and quality of life were assessed as secondary outcomes. Results: Seven prospective randomized or observational studies (2500 patients) were included, with a mean (SD) participant age of 61.2 (2.1) years. CTO-PCI was associated with significantly improved quality-of-life metrics during a mean (SD) follow-up of 14.8 (16.3) months. In patients with successful procedures, angina episodes became less frequent (mean [SD] difference for SAQ angina frequency of 12.9 [3.1] survey points [95% CI, 7.1-19.8 survey points]; standardized mean difference was 0.54 [95% CI, 0.21-0.92]; P = .002; I2 = 86.4%) and they experienced less physical activity limitation (mean [SD] difference for SAQ physical limitation of 9.7 [6.2] survey points [95% CI, 3.5-16.2 survey points]; standardized mean difference was 0.42 [95% CI, 0.24-0.55]; P < .001; I2 = 20.9%), and greater quality-of-life domain (mean [SD] difference for SAQ quality of life of 14.9 [3.5] survey points [95% CI, 7.7-22.5 survey points]; standardized mean difference was 0.41 [95% CI, 0.25-0.61]; P < .001; I2 = 58.8%) compared with patients with optimal medical therapy or failed procedure. Furthermore, follow-up duration (point estimate, 0.03; 95% CI, 0.01-0.04; P = .01) was associated with a significant decrease in angina frequency in meta-regression analysis. Conclusions and Relevance: In this systematic review and meta-analysis examining quality of life following CTO-PCI, successful procedures were associated with improved quality-of-life parameters compared with patients on optimal medical therapy or after failed CTO-PCI. These findings suggest support for using PCI to treat CTOs in symptomatic patients unresponsive to medical treatment.

Validation of the new PROGRESS-CTO complication risk scores in the OPEN-CTO registry.

BACKGROUND: Risk stratification before chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is important to inform procedural planning as well as patients and their families. We sought to externally validate the PROGRESS-CTO complication risk scores in the OPEN-CTO registry. METHODS: OPEN-CTO is a prospective registry of 1000 consecutive CTO PCIs performed at 12 experienced US centers using the hybrid algorithm. Endpoints of interest were in-hospital all-cause mortality, need for pericardiocentesis, acute myocardial infarction (MI), and major adverse cardiovascular events (MACE) (a composite of all-cause mortality, stroke, periprocedural MI, urgent repeat revascularization, and tamponade requiring pericardiocentesis). Model discrimination was assessed with the area under the curve (AUC) method, and calibration with the observed-versus-predicted probability method. RESULTS: Mean age was 65.4 ± 10.3 year, and 36.5% of patients had prior coronary artery bypass graft. Overall, 41 patients (4.1%) suffered MACE, 9 (0.9%) mortality, 26 (2.6%) acute MI, and 11 (1.1%) required pericardiocentesis. Technical success was achieved in 86.3%. Patients who experienced MACE had higher anatomic complexity, and more often required antegrade dissection/reentry and the retrograde approach. Increasing PROGRESS-CTO MACE scores were associated with increasing MACE rates: 0.5% (score 0-1), 2.4% (score 2), 3.7% (score 3), 4.5% (score 4), 7.8% (score 5), 13.0% (score 6-7). The AUC were as follows: MACE 0.72 (95% confidence interval [CI]: 0.66-0.78), mortality 0.79 (95% CI: 0.66-0.95), pericardiocentesis 0.71 (95% CI: 0.60-0.82), and acute MI 0.57 (95% CI: 0.49-0.66). Calibration was adequate for MACE and mortality, while the models underestimated the risk of pericardiocentesis and acute MI. CONCLUSIONS: In a large external cohort of patients treated with the hybrid algorithm by experienced CTO operators, the PROGRESS-CTO MACE, mortality, and pericardiocentesis risk scores showed good discrimination, while the acute MI score had inferior performance.

Predicting Residual Angina After Chronic Total Occlusion Percutaneous Coronary Intervention: Insights from the OPEN-CTO Registry.

Background Given that percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) is indicated primarily for symptom relief, identifying patients most likely to benefit is critically important for patient selection and shared decision-making. Therefore, we identified factors associated with residual angina frequency after CTO PCI and developed a model to predict postprocedure anginal burden. Methods and Results Among patients in the OPEN-CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures) registry, we evaluated the association between patient characteristics and residual angina frequency at 6 months, as assessed by the Seattle Angina Questionnaire Angina Frequency Scale. We then constructed a prediction model for angina status after CTO PCI using ordinal regression. Among 901 patients undergoing CTO PCI, 28% had no angina, 31% had monthly angina, 30% had weekly angina, and 12% had daily angina at baseline. Six months later, 53% of patients had a ≥20-point increase in Seattle Angina Questionnaire Angina Frequency Scale score. The final model to predict residual angina after CTO PCI included baseline angina frequency, baseline nitroglycerin use frequency, dyspnea symptoms, depressive symptoms, number of antianginal medications, PCI indication, and presence of multiple CTO lesions and had a C index of 0.78. Baseline angina frequency and nitroglycerin use frequency explained 71% of the predictive power of the model, and the relationship between model components and angina improvement at 6 months varied by baseline angina status. Conclusions A 7-component OPEN-AP (OPEN-CTO Angina Prediction) score can predict angina improvement and residual angina after CTO PCI using variables commonly available before intervention. These findings have implications for appropriate patient selection and counseling for CTO PCI.

Contemporary Evidence-Based Diagnosis and Management of Severe Coronary Artery Calcification.

Percutaneous treatment of heavily calcified coronary lesions remains a challenge for interventional cardiologists with increased risk of incomplete lesion preparation, suboptimal stent deployment, procedural complications, and a higher rate of acute and late stent failure. Adequate lesion preparation through calcium modification is crucial in optimising procedural outcomes. Several calcium modification devices and techniques exist, with rotational atherectomy the predominant treatment for severely calcified lesions. Novel technologies such as intravascular lithotripsy are now available and show promise as a less technical and highly effective approach for calcium modification. Emerging evidence also emphasises the value of detailed characterisation of calcification severity and distribution especially with intracoronary imaging for appropriate device selection and individualised treatment strategy. This review aims to provide an overview of the non-invasive and invasive evaluation of coronary calcification, discuss calcium modification techniques and propose an algorithm for the management of calcified coronary lesions.

Development and validation of a prediction model for angiographic perforation during chronic total occlusion percutaneous coronary intervention: OPEN-CLEAN perforation score.

BACKGROUND: Perforation is the most frequent complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and is associated with adverse events including mortality. METHODS: Among 1,000 consecutive patients enrolled in 12 center prospective CTO PCI study (OPEN CTO), all perforations were reviewed by the angiographic core-lab. Eighty-nine patients (8.9%) with angiographic perforation were compared to 911 patients without perforation. We sought to describe the clinical and angiographic predictors of angiographic perforation during CTO PCI and develop a risk prediction model. RESULTS: Among eight clinically important candidate variables, independent risk factors for perforation included prior CABG (OR 2.0 [95% CI, 1.2-3.3], p < .01), occlusion length (OR 1.2 per 10 mm increase [95% CI, 1.1-1.3], p < .01), ejection fraction (OR 1.2 per 10% decrease [95% CI, 1.1-1.5], p < .01), age (OR 1.3 per 5 year increase [95%CI, 1.1-1.5], p < .01), and heavy calcification (OR 1.7 [95% CI, 1.0-2.7], p = .04). Three other potential candidate variables, glomerular filtration rate, proximal cap ambiguity, and target vessel, were not independently associated with perforation. The model was internally validated using bootstrapping methods. From the full model, a simplified perforation prediction score (OPEN-CLEAN score: CABG, Length [occlusion], EF < 50%, Age, CalcificatioN) was developed, which discriminated the risk of angiographic perforation well (c-statistics = 0.75) and demonstrated good calibration. CONCLUSION: This simple 5-variable prediction score may help CTO operators to risk-stratify patients for angiographic perforation using variables available prior to CTO PCI procedures.

Clinical and health status outcomes among patients treated with single as compared to multivessel angioplasty during chronic total occlusion percutaneous coronary interventions: a report from the OPEN CTO registry.

BACKGROUND: Patients with coronary chronic total occlusions (CTO) often have multivessel coronary artery disease. We utilized the OPEN CTO study to evaluate patients who underwent single-vessel versus multivessel percutaneous coronary intervention (PCI) during CTO PCI. METHODS: Patients were considered to have undergone single-vessel CTO PCI if they underwent target-vessel only CTO PCI. Patients who underwent multivessel PCI during their index CTO PCI procedure were considered to have undergone multivessel PCI. The additional lesions treated in the multivessel group could be either a separate CTO lesion in a separate epicardial vessel or PCI attempt of any non-CTO stenosis during the same index procedure. Multivariate regression models were used to evaluate predictors of technical success, in-hospital major adverse cardiac and cerebrovascular events (MACCE), and health status measures. RESULTS: Eighty hundred twenty-one patients underwent single-vessel CTO PCI and 179 (17.9%) underwent multivessel PCI during their CTO PCI procedure. Baseline comorbidities, index CTO lesion complexity, and successful crossing strategies used were similar between the two groups. Total procedural time (142.6 versus 115.9 minutes, P < 0.01) and contrast administered (293.8 versus 255.0 ml, P < 0.01) were increased in the multivessel CTO PCI group. Single-vessel versus multivessel PCI during these cases did not affect the likelihood of achieving technical success [odds ratio (OR) 1.05, 95% confidence interval (CI) 0.63-1.75] nor the risk for MACCE (OR 1.23, 95% CI 0.72-2.11). Quality of life (QOL) metrics were similar between the two groups at baseline and 30-day follow-up. CONCLUSION: There were no significant differences in technical success, in-hospital MACCE rates, or QOL metrics at 30-day follow-up for patients who underwent single-vessel versus multivessel PCI during CTO PCI.

Outcomes of retrograde chronic total occlusion percutaneous coronary intervention: A report from the OPEN-CTO registry.

OBJECTIVES: We sought to assess in-hospital and long-term outcomes of retrograde compared with antegrade-only percutaneous coronary intervention for chronic total occlusion (CTO PCI). BACKGROUND: Procedural and clinical outcomes following retrograde compared with antegrade-only CTO PCI remain unknown. METHODS: Using the core-lab adjudicated OPEN-CTO registry, we compared the outcomes of retrograde to antegrade-only CTO PCI. Primary endpoints included were in-hospital major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, stroke, myocardial infarction [MI], emergency cardiac surgery, or clinically significant perforation) and MACCE at 1-year (all-cause death, MI, stroke, target lesion revascularization, or target vessel reocclusion). RESULTS: Among 885 single CTO procedures from the OPEN-CTO registry, 454 were retrograde and 431 were antegrade-only. Lesion complexity was higher (J-CTO score: 2.7 vs. 1.9; p < .001) and technical success lower (82.4 vs. 94.2%; p < .001) in retrograde compared with antegrade-only procedures. All-cause death was higher in the retrograde group in-hospital (2 vs. 0%; p = .003), but not at 1-year (4.9 vs. 3.3%; p = .29). Compared with antegrade-only procedures, in-hospital MACCE rates (composite of all-cause death, stroke, MI, emergency cardiac surgery, and clinically significant perforation) were higher in the retrograde group (10.8 vs. 3.3%; p < .001) and at 1-year (19.5 vs. 13.9%; p = .03). In sensitivity analyses landmarked at discharge, there was no difference in MACCE rates at 1 year following retrograde versus antegrade-only CTO PCI. Improvements in Seattle Angina Questionnaire Quality of Life scores at 1-year were similar between the retrograde and antegrade-only groups (29.9 vs 30.4; p = .58). CONCLUSIONS: In the OPEN-CTO registry, retrograde CTO procedures were associated with higher rates of in-hospital MACCE compared with antegrade-only; however, post-discharge outcomes, including quality of life improvements, were similar between technical modalities.

Impact of body mass index on outcome and health status after chronic total occlusion percutaneous coronary intervention: Insights from the OPEN-CTO study.

BACKGROUND: The effect of body mass index (BMI) on the procedural outcomes and health status (HS) change after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is largely unknown. METHODS: Thousand consecutive patients enrolled in a 12-center prospective CTO PCI study (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures [OPEN-CTO]) were categorized into three groups by baseline BMI (obese ≥30, overweight 25-30, and normal 18.5-25), after excluding seven patients with BMI <18.5. Baseline and follow-up HS at 1 year were quantified using the Seattle Angina Questionnaire, Rose Dyspnea Score, and Personal Health Questionnaire-8 (PHQ-8). Hierarchical, multivariable logistic, and repeated measures linear regression models were used to assess procedural success, major adverse cardiovascular and cerebrovascular events (MACCE), and HS outcomes, as appropriate. RESULTS: The obese and overweight were 47.6% and 37.4%, respectively. While procedure time and contrast dose were similar among the groups, total radiation dose (mGy) was higher with increased BMI (3,019 ± 2,027, 2,267 ± 1,714, 1,642 ± 1,223, p < .01). Procedural success rates, as well as MACCE rates, were similar among the three groups (obese 83.1%, overweight 79.8%, normal 81.9%, p = .47 and 5.1, 8.4, and 8.7%, p = .11). These rates remained similar after adjustment for baseline characteristics. The HS improvement from baseline to 12 months after adjustment was similar in obese and overweight patients compared to normal weight patients. CONCLUSIONS: CTO PCI in obese and overweight patients can be performed with similar success and complication rates. Obese and overweight patients derive similar HS benefit from CTO PCI compared to normal weight patients.

Intermediate procedural and health status outcomes and the clinical care pathways after chronic total occlusion angioplasty: A report from the OPEN-CTO (outcomes, patient health status, and efficiency in chronic total occlusion hybrid procedures) study.

BACKGROUND: No previous reports have described the comprehensive care pathways involved in chronic total occlusion percutaneous coronary intervention (CTO PCI). METHODS: In a study of 1,000 consecutive patients undergoing CTO PCI using hybrid approach, a systematic algorithm of selecting CTO PCI strategies, the procedural characteristics, complication rates, and patient reported health status outcomes through 12 months were assessed. RESULTS: Technical success of the index CTO PCI was 86%, with 89% of patients having at least one successful CTO PCI within 12 months. A total of 13.8% underwent CTO PCI of another vessel or reattempt of index CTO PCI within 1 year. At 1 year, the unadjusted major adverse cardiac and cerebral event (MACCE) rate was lower in patients with successful index CTO PCI compared to patients with unsuccessful index CTO PCI (9.4% vs. 14.6%, p = .04). The adjusted hazard ratios of myocardial infarction and death at 12 months were numerically lower in patients with successful index CTO PCI, compared to patients with unsuccessful index CTO PCI. Patients with successful index CTO PCI reported significantly greater improvement in health status throughout 12-months compared to patients with unsuccessful index CTO PCI. CONCLUSION: CTO-PCI in the real-world often require treatment of second CTO, non-CTO PCI or repeat procedures to treat initially unsuccessful lesions. Successful CTO PCI is associated with numerically lower MACCE at 1 year and persistent symptomatic improvement compared to unsuccessful CTO PCI. Understanding the relationship between the care pathways following CTO PCI and health status benefit requires further study.

Appropriate Use Criteria and Health Status Outcomes Following Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the OPEN-CTO Registry.

BACKGROUND: The American College of Cardiology/American Heart Association Appropriate Use Criteria were designed to aid clinical decision-making, yet their association with health status outcomes after chronic total occlusion percutaneous coronary intervention (PCI) is unknown. METHODS: We analyzed 769 patients with baseline and 1-year health status data after chronic total occlusion PCI. Procedures were categorized as appropriate, may be appropriate, or rarely appropriate. Mean changes in patient-reported health status, assessed by the Seattle Angina Questionnaire (SAQ), were compared across appropriate use criteria categories from baseline to 1 year. Change in SAQ summary score was stratified as little to no benefit (≤10 points), intermediate (10-19 points), large (20-29 points), and very large (≥30 points). RESULTS: The appropriate use criteria indication was appropriate in 573 patients (74.5%), may be appropriate in 191 (24.8%), and rarely appropriate in 5 (0.7%). Patients in the appropriate group reported greater improvement in SAQ summary scores (27.3±21.3 points) at 1 year compared with the may be appropriate (22.5±20.9; P=0.01). A similar pattern was noted for SAQ angina frequency (mean change 24.0±27.2 versus 18.7±25.6; P=0.02). The appropriate group had the highest proportion of very large improvements in SAQ summary scores (44.5% versus 33.3%; P=0.01). CONCLUSIONS: Among patients undergoing chronic total occlusion PCI, the rate of rarely appropriate PCI was low. The rate of appropriate PCI was high and was associated with the greatest health status improvement at 1 year. A substantial proportion of patients in the may be appropriate group experienced meaningful health status benefits as well.

Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention in Patients With Renal Dysfunction.

Although contemporary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is performed with high success rates, 10% to 13% of patients presenting with CTOs have chronic kidney disease (CKD), and the comparative safety, efficacy, and health status benefit of CTO PCI in these patients, has not been well defined. We examined the association of baseline renal function with periprocedural major adverse cardiovascular and cerebral events and health status outcomes in 957 consecutive patients (mean age 65.3 ± 10.3 years, 19.4% women, 90.3% white, 23.6 CKD [estimated glomerular filtration rate {eGFR} < 60]) in the OPEN-CTO (Outcomes, Patients Health Status, and Efficiency in Chronic Total Occlusions Registry) study. Hierarchical multivariable regression models were used to examine the independent association of baseline eGFR with technical success, periprocedural complications and change in health status, using Seattle Angina Questionnaire (SAQ) over 1 year. Crude rates of acute kidney injury were higher (13.5% vs 4.4%, p <0.001) and technical success lower (81.8% vs 88.4%, p = 0.01) in patients with CKD. There were no significant differences in other periprocedural complications. After adjustment for confounding factors, there was no significant association of baseline eGFR with technical success or periprocedural major adverse cardiovascular and cerebral events (death, myocardial infarction, emergent bypass surgery, stroke, perforation), whereas patients with lower eGFR had higher rates of acute kidney injury. The difference in SAQ summary score, between patients on the 10th and 90th percentile for baseline eGFR distribution was not clinically significant (1 month: -0.91; 1 year: -3.06 points). In conclusion, CTO PCI success, complication rates, and the health status improvement after CTO PCI are similar in patients across a range of baseline eGFRs.

Sex Differences in Instantaneous Wave-Free Ratio or Fractional Flow Reserve-Guided Revascularization Strategy.

OBJECTIVES: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies. BACKGROUND: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes. METHODS: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. RESULTS: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 ± 0.51 vs. 0.43 ± 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 ± 0.09 vs. 0.91 ± 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 ± 0.09 vs. 0.85 ± 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919). CONCLUSIONS: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038).

A Detailed Analysis of Perforations During Chronic Total Occlusion Angioplasty.

OBJECTIVES: This study sought to describe the angiographic characteristics, strategy associated with perforation, and the management of perforation during chronic total occlusion percutaneous coronary intervention (CTO PCI). BACKGROUND: The incidence of perforation is higher during CTO PCI compared with non-CTO PCI and is reportedly highest among retrograde procedures. METHODS: Among 1,000 consecutive patients who underwent CTO PCI in a 12-center registry, 89 (8.9%) had core lab-adjudicated angiographic perforations. Clinical perforation was defined as any perforation requiring treatment. Major adverse cardiac events (MAEs) were defined as in-hospital death, cardiac tamponade, and pericardial effusion. RESULTS: Among the 89 perforations, 43 (48.3%) were clinically significant, and 46 (51.7%) were simply observed. MAE occurred in 25 (28.0%), and in-hospital death occurred in 9 (10.1%). Compared with nonclinical perforations, clinical perforations were larger in size, more often at a collateral location, had a high-risk shape, and less likely to cause staining or fast filling. Compared with perforations not associated with MAE, perforations associated with MAE were larger in size, more proximal or at collateral location, and had a high-risk shape. When the core lab attributed the perforation to the approach used when the perforation occurred, 61% of retrograde perforations by other classifications were actually antegrade. CONCLUSIONS: Larger size, proximal or collateral location, and high-risk shapes of a coronary perforation were associated with MAE. Six of 10 perforations occurred with antegrade approaches among patients who had both strategies attempted. These finding will help emerging CTO operators understand high-risk features of the perforation that require treatment and inform future comparisons of retrograde and antegrade complications.

Comparison of Major Adverse Cardiac Events Between Instantaneous Wave-Free Ratio and Fractional Flow Reserve-Guided Strategy in Patients With or Without Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Invasive physiologic indices such as fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are used in clinical practice. Nevertheless, comparative prognostic outcomes of iFR-guided and FFR-guided treatment in patients with type 2 diabetes have not yet been fully investigated. Objective: To compare 1-year clinical outcomes of iFR-guided or FFR-guided treatment in patients with and without diabetes in the Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization (DEFINE-FLAIR) trial. Design, Setting, and Participants: The DEFINE-FLAIR trial is a multicenter, international, randomized, double-blinded trial that randomly assigned 2492 patients in a 1:1 ratio to undergo either iFR-guided or FFR-guided coronary revascularization. Patients were eligible for trial inclusion if they had intermediate coronary artery disease (40%-70% diameter stenosis) in at least 1 native coronary artery. Data were analyzed between January 2014 and December 2015. Interventions: According to the study protocol, iFR of 0.89 or less and FFR of 0.80 or less were used as criteria for revascularization. When iFR or FFR was higher than the prespecified threshold, revascularization was deferred. Main Outcomes and Measures: The primary end point was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. The incidence of MACE was compared according to the presence of diabetes in iFR-guided and FFR-guided groups. Results: Among the total trial population (2492 patients), 758 patients (30.4%) had diabetes. Mean age of the patients was 66 years, 76% were men (1868 of 2465), and 80% of patients presented with stable angina (1983 of 2465). In the nondiabetes population (68.5%; 1707 patients), iFR guidance was associated with a significantly higher rate of deferral of revascularization than the FFR-guided group (56.5% [n = 477 of 844] vs 46.6% [n = 402 of 863]; P < .001). However, it was not different between the 2 groups in the diabetes population (42.1% [n = 161 of 382] vs 47.1% [n = 177 of 376]; P = .15). At 1 year, the diabetes population showed a significantly higher rate of MACE than the nondiabetes population (8.6% vs 5.6%; adjusted hazard ratio [HR], 1.88; 95% CI, 1.28-2.64; P < .001). However, there was no significant difference in MACE rates between iFR-guided and FFR-guided groups in both the diabetes (10.0% vs 7.2%; adjusted HR, 1.33; 95% CI, 0.78-2.25; P = .30) and nondiabetes population (4.7% vs 6.4%; HR, 0.83; 95% CI, 0.51-1.35; P = .45) (interaction P = .25). Conclusions and Relevance: The diabetes population showed significantly higher risk of MACE than the nondiabetes population, even with the iFR-guided or FFR-guided treatment. The iFR-guided and FFR-guided treatment showed comparable risk of MACE and provided equal safety in selecting revascularization target among patients with diabetes. Trial Registration: ClinicalTrials.gov identifier: NCT02053038.

Patient Characteristics Associated With Antianginal Medication Escalation and De-Escalation Following Chronic Total Occlusion Percutaneous Coronary Intervention.

Background Prior research has shown that providers may infrequently adjust antianginal medications (AAMs) following chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Patient characteristics associated with AAM titration and the variation in postprocedure AAM management after CTO PCI across hospitals have not been reported. We sought to determine the frequency and potential correlates of AAM escalation and de-escalation after CTO PCI. Methods and Results Using the 12-center OPEN CTO registry (Outcomes, Patient Health Status, and Efficiency iN Chronic Total Occlusion Hybrid Procedures), we assessed AAM use at baseline and 6 months after CTO PCI. Escalation was defined as any addition of a new class of AAM or dose increase, whereas de-escalation was defined as a reduction in the number of AAMs or dose reduction. Angina was assessed 6 months after the index CTO PCI attempt using the Seattle Angina Questionnaire Angina Frequency domain. Potential correlates of AAM escalation (vs no change) or de-escalation (vs no change) were evaluated using multivariable modified Poisson regression models. Adjusted variation across sites was evaluated using median rate ratios. AAMs were escalated in 158 (17.5%), de-escalated in 351 (39.0%), and were unchanged at 6-month follow-up in 392 (43.5%). Patient characteristics associated with escalation included lung disease, ongoing angina, and periprocedural major adverse cardiac and cerebral events (periprocedural myocardial infarction, stroke, death, emergent cardiac surgery, or clinically significant perforation), whereas de-escalation was more frequent among patients taking more AAMs, those treated with complete revascularization, and after treatment of non-CTO lesions at the time of the index procedure. There was minimal variation in either escalation (median rate ratio, 1.11; P=0.36) or de-escalation (median rate ratio, 1.10; P=0.20) compared to no change of AAMs across sites. Conclusions Escalation or de-escalation of AAMs was less common than continuation following CTO PCI, with little variation across sites. Further research is needed to identify patients who may benefit from AAM titration after CTO PCI and develop strategies to adjust these medications in follow-up. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02026466.

De-escalation of antianginal medications after successful chronic total occlusion percutaneous coronary intervention: Frequency and relationship with health status.

BACKGROUND: Successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can markedly reduce angina symptom burden, but many patients often remain on multiple antianginal medications (AAMs) after the procedure. It is unclear when, or if, AAMs can be de-escalated to prevent adverse effects or limit polypharmacy. We examined the association of de-escalation of AAMs after CTO PCI with long-term health status. METHODS: In a 12-center registry of consecutive CTO PCI patients, health status was assessed at 6 months after successful CTO PCI with the Seattle Angina Questionnaire and the Rose Dyspnea Scale. Among patients with technical CTO PCI success, we examined the association of AAM de-escalation with 6-month health status using multivariable models adjusting for revascularization completeness and predicted risk of post-PCI angina (using a validated risk model). We also examined predictors and variability of AAMs de-escalation. RESULTS: Of 669 patients with technical success of CTO PCI, AAMs were de-escalated in 276 (35.9%) patients at 1 month. Patients with AAM de-escalation reported similar angina and dyspnea rates at 6 months compared with those whose AAMs were reduced (any angina: 22.5% vs 20%, P = .43; any dyspnea: 51.8% vs 50.1%, P = .40). In a multivariable model adjusting for complete revascularization and predicted risk of post-PCI angina, de-escalation of AAMs at 1 month was not associated with an increased risk of angina, dyspnea, or worse health status at 6 months. CONCLUSIONS: Among patients with successful CTO PCI, de-escalation of AAMs occurred in about one-third of patients at 1 month and was not associated with worse long-term health status.

Quality of Life Changes After Chronic Total Occlusion Angioplasty in Patients With Baseline Refractory Angina.

BACKGROUND: Health status and quality of life improvement after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) among patients with refractory angina has not been reported. We sought to determine the degree of quality of life improvement after CTO PCI in patients with refractory angina. METHODS AND RESULTS: Among 1000 consecutive patients who underwent CTO PCI in a 12-center registry, refractory angina was defined as any angina (baseline Seattle Angina Questionnaire [SAQ] Angina Frequency score of ≤90) despite treatment with ≥3 antianginal medications. Health status at baseline and 1-year follow-up was quantified using the SAQ. Refractory angina was present at baseline in 148 patients (14.8%). Technical success was achieved in 120 (81.1%) at the initial attempt and major adverse cardiac and cerebral events occurred in 10 (6.8%). There were no procedural deaths. Refractory angina patients were highly symptomatic at baseline with mean SAQ Angina Frequency of 51.1±23.8, SAQ quality of life of 35.3±21.2, and SAQ Summary Score of 47.2±17.9, improving by 32.0±27.8, 35.7±23.9, and 32.1±20.1 at 1 year. Through 1-year follow-up, patients with successful CTO PCI had significantly larger degree of improvement of SAQ Angina Frequency and SAQ Summary Score (35.0±26.8 versus 18.8±28.9, P<0.01; 34.2±19.4 versus 22.5±20.8, P<0.01) compared with unsuccessful CTO PCI. CONCLUSIONS: Refractory angina was present in 1 of 7 patients in the OPEN-CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures) registry. Patients with refractory angina experienced large, clinically significant health status improvements that persisted through 12 months, and patients with successful CTO PCI had larger health status improvement than those without.

Depression and Angina Among Patients Undergoing Chronic Total Occlusion Percutaneous Coronary Intervention: The OPEN-CTO Registry.

OBJECTIVES: This study sought to examine depression prevalence among chronic total occlusion (CTO) patients and compared symptom improvement among depressed and nondepressed patients after percutaneous coronary intervention (PCI). BACKGROUND: Depression in cardiovascular patients is common, but its prevalence among CTO patients and its association with PCI response is understudied. METHODS: Among 811 patients from the OPEN-CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures) registry, we evaluated change in health status between baseline and 1-year post-PCI, as measured by the Seattle Angina Questionnaire (SAQ) and the Rose Dyspnea Score. Depression was defined using the Personal Health Questionnaire-8. The independent association between health status and depression following PCI was assessed using multivariable regression. RESULTS: Among the 811 patients, 190 (23%) screened positive for major depression, of whom 6.3% were on antidepressant therapy at intervention. Depressed patients experienced more baseline angina, but by 1-year post-PCI they experienced greater improvements than nondepressed patients (change in SAQ Summary: 31.4 ± 22.4 vs. 24.2 ± 20.0; p < 0.001). After adjustment, baseline depressed patients had more improvement in health status (adjusted difference in SAQ Summary improvement, depressed vs. nondepressed: 5.48 ± 1.81; p = 0.003). CONCLUSIONS: Depression is common among CTO PCI patients, but few were treated with antidepressants at baseline. Depressed patients had more severe baseline angina and significant improvement in health status after PCI. (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion [OPEN-CTO]; NCT02026466).