Chronic Total Occlusion is Not a Risk Factor for Mortality in Patients With Successful Percutaneous Coronary Intervention: A Cohort Study.

Background Fifteen percent of patients with coronary artery disease undergoing angiography have a chronic total occlusion (CTO). The current study aimed to investigate the long-term prognosis after successful and unsuccessful CTO percutaneous coronary intervention (PCI) compared with PCI for non-CTO lesions. Methods and Results The current study was designed as an observational, region-wide, register-based cohort study enrolling all patients undergoing PCI in the Central Region of Denmark in 2009 to 2019. Patients were stratified into non-CTO, successful CTO, and unsuccessful CTO revascularization. Patients were followed until an event or January 1, 2022. The primary end point was all-cause mortality. In 21 141 patients enrolled, 2108 underwent CTO PCI. Clinical presentation was acute coronary syndrome in 11 879 patients and chronic coronary syndrome in 7887 patients. After a median of 5.7 years (interquartile range, 3.3-8.8), long-term all-cause mortality was higher after CTO PCI compared with non-CTO PCI, but the difference was statistically insignificant when adjusting for clinical factors (unadjusted hazard ratio [HR], 1.19 [95% CI, 1.09-1.29], adjusted HR, 1.08 [95% CI, 0.97-1.20]; P=0.165). After successful CTO PCI, no difference compared with non-CTO PCI was observed (unadjusted HR, 0.99 [95% CI, 0.90-1.10], adjusted HR, 0.99 [95% CI, 0.87-1.12]; P=0.873). After unsuccessful CTO PCI, long-term all-cause mortality was higher than non-CTO PCI (unadjusted HR, 1.82 [95% CI, 1.59-2.08], adjusted HR, 1.35 [95% CI, 1.13-1.63]; P<0.001). Conclusions Patients undergoing PCI for CTO have elevated long-term mortality compared with patients without CTO. Successful opening of the CTO(s) is associated with equal mortality compared with non-CTO PCI. In contrast, failed CTO PCI is associated with worse long-term mortality. These findings suggest the need for CTO programs with high success rates and low complication rates.

Comparison of definitions of coronary artery reference sizes and effects on stent selection and evaluation of stent expansion.

Accurate determination of coronary reference size is essential for optimal stent selection and evaluation of stent expansion during percutaneous coronary intervention (PCI). Several approaches for reference size estimation have been published with no universal agreement. The aim of this study was to investigate if potential differences in coronary reference size estimation lead to differences in stent and balloon selection and in detection of stent under expansion. Definitions for coronary reference size estimation, stent size selection, and stent expansion were identified in 17 randomized controlled trials. The identified methods were applied in a population of 32 clinical cases. Reference size estimates ranged up to 1.35mm, and indicated nominal stent size ranged up to 1.0 mm in the same case depending on method. Mean relative stent expansion ranged from 54±12% to mean 100±29% depending on the applied reference method. Choice of method for reference size estimation using intravascular imaging may influence stent selection and greatly affects evaluation of post-PCI stent expansion.

Coronary Artery Stenosis Evaluation by Angiography-Derived FFR: Validation by Positron Emission Tomography and Invasive Thermodilution.

BACKGROUND: Fractional flow reserve (FFR) derived from invasive coronary angiography (QFR) is promising for evaluation of intermediate coronary artery stenosis. OBJECTIVES: The authors aimed to compare the diagnostic performance of QFR and the guideline-recommended invasive FFR using 82Rubidium positron emission tomography (82Rb-PET) myocardial perfusion imaging as reference standard. METHODS: This is a prospective, observational study of symptomatic patients with suspected obstructive coronary artery disease on coronary computed tomography angiography (≥50% diameter stenosis in ≥1 vessel). All patients were referred to 82Rb-PET and invasive coronary angiography with FFR and QFR assessment of all intermediate (30%-90% diameter stenosis) stenoses. Main analyses included a comparison of the ability of QFR and FFR to identify reduced myocardial blood flow (<2 mL/g/min) during vasodilation and/or relative perfusion abnormalities (summed stress score ≥4 in ≥2 adjacent segments). RESULTS: A total of 250 patients (320 vessels) with indication for invasive physiological assessment were included. The continuous relationship of 82Rb-PET stress myocardial blood flow per 0.10 increase in FFR was +0.14 mL/g/min (95% CI: 0.07-0.21 mL/g/min) and +0.08 mL/g/min (95% CI: 0.02-0.14 mL/g/min) per 0.10 QFR increase. Using 82Rb-PET as reference, QFR and FFR had similar diagnostic performance on both a per-patient level (accuracy: 73%; 95% CI: 67%-79%; vs accuracy: 71%; 95% CI: 64%-78%) and per-vessel level (accuracy: 70%; 95% CI: 64%-75%; vs accuracy: 68%; 95% CI: 62%-73%). The per-vessel feasibility was 84% (95% CI: 80%-88%) for QFR and 88% (95% CI: 85%-92%) for FFR by intention-to-diagnose analysis. CONCLUSIONS: With 82Rb-PET as reference modality, the wire-free QFR solution showed similar diagnostic accuracy as invasive FFR in evaluation of intermediate coronary stenosis. (DAN-NICAD - Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease; NCT02264717).

Early and long-term prognosis in patients with remaining chronic total occlusions after revascularization attempt. A cohort study from the SKEJ-CTO registry.

OBJECTIVES: The present study aimed to compare safety and long-term prognosis of patients with chronic total coronary occlusions (CTO) stratified for remaining CTOs after percutaneous coronary intervention (PCI). DESIGN: The study cohort consisted of patients with coronary artery disease who underwent CTO PCI in a high volume tertiary center from 2009 to 2019 and were registered in Danish high-quality registers. Patients with successful PCI of all CTOs were compared to patients with ≥1 remaining CTO post-procedural. Primary endpoints were analysed using Cox-regression and Kaplan-Meier estimates, and included all-cause mortality, major adverse cardio- and cerebrovascular events (MACCE) and a 30-day safety endpoint. RESULTS: Procedural success rate was 87.7%, and 76.5% of patients had all CTO(s) opened post-PCI. Safety endpoint occurred in 4.6% of patients, and more frequently in patients with remaining CTO(s) (RD 4.9, 95%CI 0.1, 9.8). All-cause mortality was higher in patients with remaining CTO(s) (Unadjusted HR 1.65, 95% CI 1.03, 2.47, p = .015. Adjusted HR 1.32, 95%CI 0.88-1.99, p = .18) after eight years of follow-up. Risk of MACCE was significantly higher in patients with remaining CTO(s) (Unadjusted HR 1.79, 95% CI 1.34-2.41, p < .001. Adjusted HR 1.51, 95% CI 1.11-2.05, p = .009). CONCLUSIONS: In our centre, CTO PCI was associated with high success rate and low risk of 30-days complications. Presence of remaining CTO(s) after final revascularization attempt was associated with higher but statistically insignificant long-term mortality but was an independent predictor of MACCE.

Validation of a semi-automatic software for optical coherence tomography - analysis in heart transplanted patients.

Optical Coherence Tomography (OCT) is an intravascular imaging modality enabling detailed evaluation of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). However, its clinical application remains hampered by time-consuming manual quantitative analysis. We aimed to validate a semi-automated quantitative OCT analysis software (Iowa Coronary Wall Analyzer, ICWA-OCT) to improve OCT-analysis in HTx patients. 23 patients underwent OCT evaluation of all three major coronary arteries at 3 months (3M) and 12 months (12M) after HTx. We analyzed OCT recordings using the semiautomatic software and compared results with measurements from a validated manual software. For semi-automated analysis, 31,228 frames from 114 vessels were available. The validation was based on a subset of 4287 matched frames. We applied mixed model statistics to accommodate the multilevel data structure with method as a fixed effect. Lumen (minimum, mean, maximum) and media (mean, maximum) metrics showed no significant differences. Mean and maximum intima area were underestimated by the semi-automated method (ß-methodmean = - 0.289 mm2, p < 0.01; ß-methodmax = - 0.695 mm2, p < 0.01). Bland-Altman analyses showed increasing semi-automatic underestimation of intima measurements with increasing intimal extent. Comparing 3M to 12M progression between methods, mean intimal area showed minor underestimation (ß-methodmean = - 1.03 mm2, p = 0.04). Lumen and media metrics showed excellent agreement between the manual and semi-automated method. Intima metrics and progressions from 3M to 12M were slightly underestimated by the semi-automated OCT software with unknown clinical relevance. The semi-automated software has the future potential to provide robust and time-saving evaluation of CAV progression.

Predictive value of post-percutaneous coronary intervention fractional flow reserve: a systematic review and meta-analysis.

AIMS: We aimed to investigate the relationship between post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) and clinical outcome using a systematic review with a study-level meta-analysis. METHODS AND RESULTS: MEDLINE, Embase, and CENTRAL were systematically searched for articles with clinical follow-up reporting mean or median final post-PCI FFR. The main outcome was a composite of major adverse cardiac events (MACE) including all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR). Meta-regression analyses were performed on mean post-PCI FFR values. A total of 62 studies with 12 340 patients and 12 923 stented vessels were included, with follow-ups ranging from 1 to 89 months. Post-PCI FFR was not continuously associated with the rate of 1-year MACE or 1-year TVR using meta-regression models accounting for heterogeneous follow-up lengths. For studies comparing high vs. low post-PCI FFR, low post-PCI FFR was associated with high risk ratio for MACE {1.97 [95% confidence interval (CI):1.45-2.67]}, all-cause death [1.59 (95% CI: 1.08-2.34)], MI [3.18 (95% CI: 1.84-5.50)], TVR [2.08 (95% CI: 1.63-2.65)] and angina status [2.50 (95% CI: 1.53-4.06)] using different optimal cut-off values spanning from 0.80 to 0.95. CONCLUSION: We found no clear continuous association between post-PCI FFR and clinical outcomes in this systematic study-level meta-analysis. In a subset of studies investigating binary classification, high post-PCI FFR was associated with a better clinical outcome than low post-PCI FFR.We investigated the relationship between post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) and rate of major adverse cardiac events (MACE), including all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR), using a systematic review and study-level meta-analysis, pooling 12 340 patients from 62 studies. Mean post-PCI FFR was not continuously associated with a 1-year MACE rate accounting for heterogenous follow-up lengths. Still, the risk ratio favoured high post-PCI FFR for reduced MACE, all-cause death, MI, TVR, and better angina status using different cut-offs.

Cost-Effectiveness in Patients Undergoing Revascularization of Chronic Total Occluded Coronary Arteries-A Cohort Study.

Background: Revascularization of patients with chronic total occluded coronary arteries (CTO) is recommended if they have symptoms despite medical treatment. The cost-effectiveness of treatment with percutaneous coronary intervention (PCI) was investigated in this cohort study. Materials and Methods: The study was designed as a cohort study enrolling all patients undergoing PCI for a CTO in the Central Region of Denmark and recorded in the EUROCTO database. Major adverse cardio- and cerebrovascular events (MACCE) and admissions for cardiac symptoms were collected in the Western Denmark Heart Registry and through medical Journal Audits. Exposure was defined as successful revascularization of all CTO lesions compared with having one or more remaining CTOs after PCI attempt(s). Cost-effectiveness was evaluated as the net benefit (NB) at the patient level 3 years after treatment and through cost-effectiveness planes. The cost was defined as the cumulative cost of the index procedure and admissions due to MACCE and cardiac symptoms. Effectiveness was defined as the difference in MACCE for the primary analysis and the difference in death and symptomatic admissions for the secondary. Results: Between 2009 and 2019, 441 patients with ≥ 3 years of follow-up were treated with PCI for at least one CTO lesion (342 in the successful arm and 99 in the unsuccessful arm). The technical success rate was 85.4%. In total, 155 MACCE and 184 symptomatic admissions occurred in the follow-up period. The mean total cost was EUR 11.719 (11.034; 12.406) in the successful group vs. EUR 13.565 (11.899; 15,231) (p = 0.02) in the unsuccessful group. Net-benefit was EUR 1.846 (64; 3,627) after successful revascularization for MACCE. The adjusted analysis found an NB of EUR 1,481 (-118; 3,079). Bootstrap estimates showed cost-effectiveness planes in favor of successful revascularization. Conclusion: Patients fully revascularized for all CTO lesions had a more cost-efficient treatment. However, results need confirmation in a randomized controlled trial due to the risk of residual confounding after adjustment.

Reproducibility of quantitative flow ratio: the QREP study.

BACKGROUND: Quantitative flow ratio (QFR) is a tool for physiological lesion assessment based on invasive coronary angiography. AIMS: We aimed to assess the reproducibility of QFR computed from the same angiograms as assessed by multiple observers from different, international sites. METHODS: We included 50 patients previously enrolled in dedicated QFR studies. QFR was computed twice, one month apart by five blinded observers. The main analysis was the coefficient of variation (CV) as a measure of intra- and inter-observer reproducibility. Key secondary analysis was the identification of clinical and procedural characteristics predicting reproducibility. RESULTS: The intra-observer CV ranged from 2.3% (1.5-2.8) to 10.2% (6.6-12.0) among the observers. The inter-observer CV was 9.4% (8.0-10.5). The QFR observer, low angiographic quality, and low fractional flow reserve (FFR) were independent predictors of a large absolute difference between repeated QFR measurements defined as a difference larger than the median difference (>0.03). CONCLUSIONS: The inter- and intra-observer reproducibility for QFR computed from the same angiograms ranged from high to poor among multiple observers from different sites with an average agreement of 0.01±0.08 for repeated measurements. The reproducibility was dependent on the observer, angiographic quality and the coronary artery stenosis severity as assessed by FFR.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non-inferiority NOBLE trial.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used in revascularisation of patients with left main coronary artery disease in place of the standard treatment, coronary artery bypass grafting (CABG). The NOBLE trial aimed to evaluate whether PCI was non-inferior to CABG in the treatment of left main coronary artery disease and reported outcomes after a median follow-up of 3·1 years. We now report updated 5-year outcomes of the trial. METHODS: The prospective, randomised, open-label, non-inferiority NOBLE trial was done at 36 hospitals in nine northern European countries. Patients with left main coronary artery disease requiring revascularisation were enrolled and randomly assigned (1:1) to receive PCI or CABG. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, repeat revascularisation, and stroke. Non-inferiority of PCI to CABG was defined as the upper limit of the 95% CI of the hazard ratio (HR) not exceeding 1·35 after 275 MACCE had occurred. Secondary endpoints included all-cause mortality, non-procedural myocardial infarction, and repeat revascularisation. Outcomes were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were enrolled and allocated to PCI (n=598) or CABG (n=603), with 17 subsequently lost to early follow-up. 592 patients in each group were included in this analysis. At a median of 4·9 years of follow-up, the predefined number of events was reached for adequate power to assess the primary endpoint. Kaplan-Meier 5-year estimates of MACCE were 28% (165 events) for PCI and 19% (110 events) for CABG (HR 1·58 [95% CI 1·24-2·01]); the HR exceeded the limit for non-inferiority of PCI compared to CABG. CABG was found to be superior to PCI for the primary composite endpoint (p=0·0002). All-cause mortality was estimated in 9% after PCI versus 9% after CABG (HR 1·08 [95% CI 0·74-1·59]; p=0·68); non-procedural myocardial infarction was estimated in 8% after PCI versus 3% after CABG (HR 2·99 [95% CI 1·66-5·39]; p=0·0002); and repeat revascularisation was estimated in 17% after PCI versus 10% after CABG (HR 1·73 [95% CI 1·25-2·40]; p=0·0009). INTERPRETATION: In revascularisation of left main coronary artery disease, PCI was associated with an inferior clinical outcome at 5 years compared with CABG. Mortality was similar after the two procedures but patients treated with PCI had higher rates of non-procedural myocardial infarction and repeat revascularisation. FUNDING: Biosensors.