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Atrial Fibrillation and Chronic Total Occlusion Percutaneous Coronary Intervention Outcomes: Insights From the PROGRESS-CTO Registry
ABSTRACT
BACKGROUND. We examined the effect of atrial fibrillation on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS. We examined the baseline characteristics and procedural outcomes of 9,166 CTO PCIs performed at 39 US and non-US centers between 2012 and 2023. RESULTS. Atrial fibrillation was present in 1122 (12%) patients. These patients were older and had a higher incidence of comorbidities, such as hypertension, dyslipidemia, heart failure, cerebrovascular disease, and peripheral arterial disease, lower left ventricular ejection fraction, and lower eGFR. Their CTOs were more likely to have moderate to severe calcification and longer lesion length. They also had higher mean J-CTO and PROGRESS-CTO complications (Acute MI, MACE, Mortality, Perforation, and Pericardiocentesis) scores. Patients with atrial fibrillation had higher prevalence of uncrossable and undilatable CTO lesions and required longer procedure (107 vs 119 min; P<.001) and fluoroscopy (40 vs 43 min; P=.005) time. Technical success and MACE, including procedural/in-hospital bleeding, were similar in patients with and without atrial fibrillation. Although the crude incidence of MACE on follow-up (median 61 days) was significantly higher in patients with atrial fibrillation, the latter was not independently associated with adverse events on Cox proportional hazards analysis. CONCLUSIONS. Patients with atrial fibrillation undergoing CTO PCI are older, have more comorbidities, higher lesion complexity, and longer procedure time, but similar technical success and in-hospital MACE. They have higher MACE and mortality during follow-up, but the difference is not significant after adjusting for potential confounding variables.
INTRODUCTION
Atrial fibrillation is the most common cardiac arrythmia and a common comorbidity among patients undergoing percutaneous coronary intervention (PCI) and is associated with higher in-hospital mortality and incidence of adverse outcomes.1-3 The impact of atrial fibrillation on the outcomes of chronic total occlusion (CTO) PCI has received limited study.4 We analyzed a large, multicenter CTO PCI registry to determine the prevalence of atrial fibrillation and its impact on the procedural techniques and outcomes.
METHODS
We examined the baseline clinical and angiographic characteristics and procedural outcomes of 9166 CTO PCIs at 39 US and non-US centers between 2012 and 2023. Cases without data on atrial fibrillation (3766 cases) were excluded from the analysis. Data collection was recorded in a dedicated online database (PROGRESS CTO: Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; Clinicaltrials.gov identifier: NCT02061436). Study data were collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at the Minneapolis Heart Institute Foundation.5,6 The study was approved by the institutional review board of each center.
Coronary CTOs were defined as coronary lesions with Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow of at least 3-month duration. Estimation of the duration of occlusion was clinical, based on the first onset of angina, prior history of myocardial infarction (MI) in the target vessel territory, or comparison with a prior angiogram.
Calcification was assessed by angiography and classified as mild (spots), moderate (involving ≤50% of the reference lesion diameter), or severe (>50%). CTOs were defined according to the definition of CTO Academic Research Consortium, as absence of antegrade flow through the lesion with a presumed or documented duration of ≥3 months.7 Technical success was defined as successful CTO revascularization with achievement of <30% residual diameter stenosis within the treated segment and restoration of TIMI grade 3 antegrade flow. Procedural success was defined as the achievement of technical success without any in-hospital major adverse cardiac events (MACE). In-hospital MACE included any of the following adverse events prior to hospital discharge: death, MI, recurrent symptoms requiring urgent repeat target-vessel revascularization with PCI or coronary artery bypass graft (CABG) surgery, tamponade requiring either pericardiocentesis or surgery, and stroke. MI was defined using the Third Universal Definition of Myocardial Infarction (type 4a MI).8 Bleeding was defined in our registry as a suspected or confirmed bleeding event observed and documented in the medical record that was associated with any of the following: Hemoglobin drop of ≥3 g/dL or transfusion of whole blood or packed red blood cells or procedural intervention/surgery at the bleeding site to reverse/stop or correct the bleeding (such as surgical closures/exploration of the arteriotomy site, balloon angioplasty to seal an arterial tear, endoscopy with cautery of a gastrointestinal bleed). The Japanese CTO (J-CTO) score was calculated as described by Morino et al,9 the PROGRESS-CTO score as described by Christopoulos et al,10 the new PROGRESS-CTO complication scores (Acute MI, MACE, Mortality, and Pericardiocentesis) as described by Simsek et al,11 and the PROGRESS-CTO perforation score as described by Kostantinis et al12. The MDRD 4-variable equation was used to calculate the estimated glomerular filtration rate (eGFR = 175 × SerumCreatinine−1.154 × age−0.203 × 1.212 [if African American] × 0.742 [if female]).13
Statistical analysis. Categorical variables were expressed as percentages and were compared using the Pearson’s chi-square test. Continuous variables are presented as mean ± standard deviation or as median (interquartile range) unless otherwise specified and were compared using the independent-samples t-test for normally distributed variables and the Mann-Whitney U test for non-parametric variables, as appropriate. The effect of atrial fibrillation on follow-up MACE and mortality was examined using univariable and multivariable logistic regression. Univariable cox proportional hazards regression was performed to identify variables that might be associated with follow-up outcomes. All statistical analyses were performed using R Statistical Software, version 4.2.2 (R Foundation for Statistical Computing, Vienna, Austria). A P-value of <.05 was considered statistically significant.
RESULTS
Patient characteristics. Between 2012 and 2023, 1122 (12%) of 9166 patients who underwent CTO PCI at 39 centers had atrial fibrillation. Patients with atrial fibrillation were older, more likely to be active smokers and less likely to have family history of coronary artery disease (CAD) (Table 1). They had significantly higher incidence of comorbidities, such as hypertension, dyslipidemia, heart failure, cerebrovascular disease, and peripheral arterial disease, as well as prior history of MI, and CABG. Furthermore, they had lower eGFR and left ventricular ejection fraction.
Angiographic characteristics. Table 2 presents the angiographic characteristics of the study lesions. The right coronary artery was the most common CTO target vessel in patients with atrial fibrillation (50.4%), followed by the left anterior descending artery (27.1%) and the left circumflex artery (20%). Atrial fibrillation patients had complex angiographic characteristics, such as long lesion length and moderate to severe calcification and had higher J-CTO and PROGRESS-CTO complications (Acute MI, MACE, Mortality, Perforation, and Pericardiocentesis) scores.
Procedural characteristics. Patients with atrial fibrillation were more likely to have balloon uncrossable and balloon undilatable lesions, and their procedures required lower amount of contrast but longer procedure and fluoroscopy times (Table 3). There was no statistically significant difference between patients with and without atrial fibrillation with regards to initial crossing strategies, but the retrograde approach was more likely to be the final successful crossing strategy.
Procedural, in-hospital, and follow-up outcomes. Technical and procedural success were similar between patients with and without atrial fibrillation (Figure 1), as was the incidence of in-hospital complications including in-hospital death and bleeding (Table 4).
Follow-up data were available for 3368 patients. A total of 131 follow-up MACE events and 37 follow-up deaths were recorded during a median follow-up period of 61 days (interquartile range: 16 to 344 days). The incidence of follow-up MACE (log-rank P= .049) and follow-up mortality (log-rank P = .0013) was significantly higher in patients with atrial fibrillation (Figure 4), but on adjusted Cox proportional hazards analysis atrial fibrillation was not independently associated with higher follow-up MACE (Figure 2) and death (Figure 3).
DISCUSSION
The major findings of our study are that among patients undergoing CTO PCI those with atrial fibrillation: a) were older, b) had more comorbidities and complex angiographic characteristics, c) similar in-hospital MACE rates, procedural, and technical success, and d) similar follow-up MACE and mortality, after controlling for confounding variables.
The prevalence of atrial fibrillation reported in our registry (12%) is comparable with a prior CTO PCI study4 (8.4%) and with studies of patients undergoing PCI in general.2,3 In our cohort, atrial fibrillation was strongly associated with age, an observation well-established in the literature14, and the presence of comorbidities, that are known to be linked with atrial fibrillation such as hypertension15, dyslipidemia16, heart failure17, cerebrovascular disease18, peripheral arterial disease,19 and current smoking20-22. Moreover, our finding that patients with atrial fibrillation undergoing CTO PCI are less likely to have a family history of CAD (26.8%, 31.5%, P=.004) is consistent with the study by Stahli et al. (25% vs 38.5%, P <.001)4. In this study, CTOs of patients with atrial fibrillation were more likely to have moderate/severe calcifications (66.3% vs 55.9%, P=.006) similar to our study (51.9% vs 41.6%, P<.001) and longer fluoroscopy time (41.8 ± 37.4 vs 35.7 ± 36.8 min, P=.02).
Atrial fibrillation patients undergoing elective PCI or PCI for acute coronary syndromes had higher in-hospital mortality and incidence of adverse cardiac events1-3. However, the impact of atrial fibrillation on in-hospital outcomes following CTO PCI has been assessed in only one study of 2002 CTO PCIs performed in Germany between 2005 and 20134. In that study atrial fibrillation was associated with lower procedural success (76.3% vs 83.6%, P=.02) and higher pepriprocedural MACE (3.6% vs 1.4%, P=.04). This is different from our study that showed similar procedural success and procedural complications. The incidence of follow-up MACE and all-cause mortality was significantly higher in patients with atrial fibrillation, similar to our study. However, in the Stahli study, all-cause mortality was higher in patients with atrial fibrillation even after adjusting for potential confounders (HR 1.62, 95% CI 1.06-2.47, P=.03), while in our study the correlation was no longer significant on multivariable analysis.
Our study has limitations. The PROGRESS-CTO is an observational registry with all inherent limitations. There was no independent adjudication of clinical events and there was no core laboratory assessment of the study angiograms. Follow-up data were not available for all patients. The procedures reported in the registry were performed at centers with experienced in CTO PCI operators, potentially limiting the generalizability of the results to centers with limited CTO PCI experience. Data on anticoagulant use and long-term bleeding data were not available.
CONCLUSION
Patients with atrial fibrillation who undergo CTO PCI are older and have more comorbidities and more complex lesions compared with patients that do not have atrial fibrillation. Success rates and in-hospital MACE are however similar between groups.
ACKNOWLEDGEMENTS
The authors are grateful for the philanthropic support of our generous anonymous donors, and the philanthropic support of Drs. Mary Ann and Donald A Sens; Mrs. Diane and Dr. Cline Hickok; Mrs. Wilma and Mr. Dale Johnson; Mrs. Charlotte and Mr. Jerry Golinvaux Family Fund; the Roehl Family Foundation; the Joseph Durda Foundation. The generous gifts of these donors to the Minneapolis Heart Institute Foundation's Science Center for Coronary Artery Disease (CCAD) helped support this research project.
Affiliations and Disclosure
From the 1Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA; 2Texas Health Presbyterian Hospital, Dallas, TX, USA; 3University Hospitals, Case Western Reserve University, Cleveland, OH, USA; 4Cleveland Clinic, Cleveland, OH, USA; 5WellSpan York Hospital, York, Pennsylvania, USA; 6Massachusetts General Hospital, Boston, MA, USA; 7Oklahoma Heart Institute, Tulsa, OK, USA; 8Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA; 9Aswan Heart Center, Magdi Yacoub Foundation, Cairo, Egypt; 10North Oaks Health System, Hammond, LA, USA; 11Red Cross Hospital of Athens, Athens, Greece; 12Memorial Bahcelievler Hospital, Istanbul, Turkey; 13Biruni University Medical School, Istanbul, Turkey.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
The authors report that patient consent was provided for publication of the images used herein.
Manuscript accepted June 2, 2023.
Address for Correspondence: Emmanouil S. Brilakis, MD, PhD, Minneapolis Heart Institute, 920 E 28th Street #300, Minneapolis, Minnesota 55407. Email: esbrilakis@gmail.com
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