Treatment of elderly patients with non-ST-elevation myocardial infarction: the nationwide POPular age registry.

OBJECTIVE: We describe the current treatment of elderly patients with non-ST-elevation myocardial infarction (NSTEMI) enrolled in a national registry. METHODS: The POPular AGE registry is a prospective, multicentre study of patients ≥ 75 years of age presenting with NSTEMI, performed in the Netherlands. Management was at the discretion of the treating physician. Cardiovascular events consisted of cardiovascular death, myocardial infarction and ischaemic stroke. Bleeding was classified according to the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: A total of 646 patients were enrolled between August 2016 and May 2018. Median age was 81 (IQR 77-84) years and 58% were male. Overall, 75% underwent coronary angiography, 40% percutaneous coronary intervention, and 11% coronary artery bypass grafting, while 49.8% received pharmacological therapy only. At discharge, dual antiplatelet therapy (aspirin and P2Y12 inhibitor) was prescribed to 56.7%, and 27.4% received oral anticoagulation plus at least one antiplatelet agent. At 1­year follow-up, cardiovascular death, myocardial infarction or stroke had occurred in 13.6% and major bleeding (BARC 3 and 5) in 3.9% of patients. The risk of both cardiovascular events and major bleeding was highest during the 1st month. However, cardiovascular risk was three times as high as bleeding risk in this elderly population, both after 1 month and after 1 year. CONCLUSIONS: In this national registry of elderly patients with NSTEMI, the majority are treated according to current European Society of Cardiology guidelines. Both the cardiovascular and bleeding risk are highest during the 1st month after NSTEMI. However, the cardiovascular risk was three times as high as the bleeding risk.

The Clinical Implementation of CYP2C19 Genotyping in Patients with an Acute Coronary Syndrome: Insights From the FORCE-ACS Registry.

BACKGROUND: Guidelines recommend prasugrel or ticagrelor for acute coronary syndrome (ACS) patients. However, these P2Y12 inhibitors increase bleeding risk compared to clopidogrel. Although genotype-guided P2Y12-inhibitor selection has been shown to reduce bleeding risk, data on its clinical implementation is lacking. METHODS: The study included ACS patients receiving genotype-guided antiplatelet therapy, utilising either a point-of-care (POC) device or laboratory-based testing. We aimed to collect qualitative and quantitative data on genotyping, eligibility for de-escalation, physician adherence to genotype results, time to de-escalation and cost reduction. RESULTS: Of the 1,530 patients included in the ACS registry from 2021 to 2023, 738 ACS patients treated with ticagrelor received a CYP2C19 genotype test. The median turnover time of genotyping was 6.3 hours (interquartile range [IQR], 3.2-16.7), with 82.3% of the genotyping results known within 24 hours after admission. POC genotyping exhibited significantly shorter turnaround times compared to laboratory-based testing (with respective medians of 5.7 vs 47.8 hours; P < .001). Of the genotyped patients, 81.7% were eligible for de-escalation which was carried out within 24 hours in 70.9% and within 48 h in 93.0%. The time to de-escalation was significantly shorter using POC (25.4 hours) compared to laboratory-based testing (58.9 hours; P < .001). Implementing this strategy led to a reduction of €211,150.50 in medication costs. CONCLUSIONS: CYP2C19 genotype-guided-de-escalation in an all-comers ACS population is feasible. POC genotyping leads to shorter turnaround times and quicker de-escalation. Time to de-escalation from ticagrelor to clopidogrel in noncarriers was short, with high physician adherence to genotype results.

Conservative versus Invasive Strategy in Elderly Patients with Non-ST-Elevation Myocardial Infarction: Insights from the International POPular Age Registry.

This registry assessed the impact of conservative and invasive strategies on major adverse clinical events (MACE) in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). Patients aged ≥75 years with NSTEMI were prospectively registered from European centers and followed up for one year. Outcomes were compared between conservative and invasive groups in the overall population and a propensity score-matched (PSM) cohort. MACE included cardiovascular death, acute coronary syndrome, and stroke. The study included 1190 patients (median age 80 years, 43% female). CAG was performed in 67% (N = 798), with two-thirds undergoing revascularization. Conservatively treated patients had higher baseline risk. After propensity score matching, 319 patient pairs were successfully matched. MACE occurred more frequently in the conservative group (total population 20% vs. 12%, adjHR 0.53, 95% CI 0.37-0.77, p = 0.001), remaining significant in the PSM cohort (18% vs. 12%, adjHR 0.50, 95% CI 0.31-0.81, p = 0.004). In conclusion, an early invasive strategy was associated with benefits over conservative management in elderly patients with NSTEMI. Risk factors associated with ischemia and bleeding should guide strategy selection rather than solely relying on age.

Impact of recurrent ischaemic and bleeding events on quality of life in patients with acute coronary syndrome: Insights from the FORCE-ACS registry.

OBJECTIVE: Patients with acute coronary syndrome (ACS) remain at high risk for recurrent ischaemic and bleeding events during follow-up. Our study aimed to quantify and compare the impact of these adverse events on quality of life (QoL). METHODS: Data from patients with ACS prospectively enrolled in the FORCE-ACS registry between January 2015 and December 2019 were used for this study. The primary ischaemic and bleeding events of interest were hospital readmission for ACS and Bleeding Academic Research Consortium type 2 or 3 bleeding during 12 months follow-up. QoL was measured using the EQ-5D Visual Analogue Scale (VAS) score and the 12-item Short Form Survey version 2 derived Physical Component Summary (PCS) and Mental Health Component Summary (MCS) scores at 12 months follow-up. RESULTS: In total, 3339 patients (mean age 66.8 years, 27.9% women) were included. During follow-up, ischaemic events occurred in 202 patients (6.0%) and bleeding events in 565 patients (16.9%). After adjustment for demographic and clinical characteristics, ischaemic events remained independently associated with lower QoL regardless of metric used. Bleeding was also independently associated with lower EQ-5D VAS and PCS scores, but not with a lower MCS score. The QoL decrement associated with ischaemic events was numerically larger than the decrement associated with bleeding. CONCLUSIONS: Ischaemic and bleeding events remain prevalent and are independently associated with lower QoL at 12 months follow-up in patients previously admitted for ACS. The incidence and impact of these adverse events should be considered when balancing individual ischaemic and bleeding risks.

Effects of CYP3A4*22 and CYP3A5 on clinical outcome in patients treated with ticagrelor for ST-segment elevation myocardial infarction: POPular Genetics sub-study.

Aims: To determine the clinical efficacy, adverse events and side-effect dyspnea of CYP3A4*22 and CYP3A5 expressor status in ticagrelor treated patients. Methods and results: Ticagrelor treated patients from the POPular Genetics randomized controlled trial were genotyped for CYP3A4*22 and CYP3A5*3 alleles. Patients were divided based on their genotype. In total 1,281 patients with ST-segment elevation myocardial infarction (STEMI) were included. CYP3A4*22 carriers (n = 152) versus CYP3A4*22 non-carrier status (n = 1,129) were not found to have a significant correlation with the primary thrombotic endpoint: cardiovascular death, myocardial infarction, definite stent thrombosis and stroke [1.3% vs. 2.5%, adjusted hazard ratio 1.81 (0.43-7.62) p = 0.42], or the primary bleeding endpoint: PLATO major and minor bleeding [13.2% vs. 11.3%, adjusted hazard ratio 0.93 (0.58-1.50) p = 0.77]. Among the CYP3A4*1/*1 patients, CYP3A5 expressors (n = 196) versus non-expressors (n = 926) did not show a significant difference for the primary thrombotic [2.6% vs. 2.5%, adjusted hazard ratio 1.03 (0.39-2.71) p = 0.95], or the primary bleeding endpoint [12.8% vs. 10.9%, adjusted hazard ratio 1.13 (0.73-1.76) p = 0.58]. With respect to dyspnea, no significant difference was observed between CYP3A4*22 carriers versus CYP3A4*22 non-carriers [44.0% vs. 45.0%, odds ratio 1.04 (0.45-2.42) p = 0.93], or in the CYP3A4*1/*1 group, CYP3A5 expressors versus CYP3A5 non-expressors [35.3% vs. 47.8%, odds ratio 0.60 (0.27-1.30) p = 0.20]. Conclusion: In STEMI patients treated with ticagrelor, neither the CYP3A4*22 carriers, nor the CYP3A5 expressor status had a statistical significant effect on thrombotic and bleeding event rates nor on dyspnea. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01761786.

Dual versus triple antithrombotic therapy after percutaneous coronary intervention: the prospective multicentre WOEST 2 Study.

BACKGROUND: For patients on oral anticoagulants (OAC) undergoing percutaneous coronary intervention (PCI), European guidelines have recently changed their recommendations to dual antithrombotic therapy (DAT; P2Y12 inhibitor and OAC) without aspirin. AIMS: The prospective WOEST 2 registry was designed to obtain contemporary real-world data on antithrombotic regimens and related outcomes after PCI in patients with an indication for OAC. METHODS: In this analysis, we compare DAT (P2Y12 inhibitor and OAC) to triple antithrombotic therapy (TAT; aspirin, P2Y12 inhibitor, and OAC) on thrombotic and bleeding outcomes after one year. Clinically relevant bleeding was defined as Bleeding Academic Research Consortium classification (BARC) grade 2, 3, or 5; major bleeding as BARC grade 3 or 5. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause mortality, myocardial infarction, stent thrombosis, ischaemic stroke, and transient ischaemic attack. RESULTS: A total of 1,075 patients were included between 2014 and 2021. Patients used OAC for atrial fibrillation (93.6%) or mechanical heart valve prosthesis (4.7%). Non-vitamin K oral anticoagulants (NOAC) were prescribed in 53.1% and vitamin K antagonists in 46.9% of patients. At discharge, 60.9% received DAT, and 39.1% TAT. DAT was associated with less clinically relevant and similar major bleeding (16.8% vs 23.4%; p<0.01 and 7.6% vs 7.7%, not significant), compared to TAT. The difference in MACCE between the two groups was not statistically significant (12.4% vs 9.7%; p=0.17). Multivariable adjustment and propensity score matching confirmed these results. CONCLUSIONS: Dual antithrombotic therapy is associated with a substantially lower risk of clinically relevant bleeding without a statistically significant penalty in ischaemic events.

External validation of the GRACE risk score and the risk-treatment paradox in patients with acute coronary syndrome.

OBJECTIVES: To validate the Global Registry of Acute Coronary Events (GRACE) risk score and examine the extent and impact of the risk-treatment paradox in contemporary patients with acute coronary syndrome (ACS). METHODS: Data from 5015 patients with ACS enrolled in the FORCE-ACS registry between January 2015 and December 2019 were used for model validation. The performance of the GRACE risk score for predicting in-hospital and 1-year mortality was evaluated based on indices of model discrimination and calibration. Differences in the delivery of guideline-recommended care among patients who survived hospitalisation (n=4911) per GRACE risk stratum were assessed and the association with postdischarge mortality was examined. RESULTS: Discriminative power of the GRACE risk score was good for predicting in-hospital (c-statistic: 0.86; 95% CI: 0.83 to 0.90) and 1-year mortality (c-statistic: 0.82; 95% CI: 0.79 to 0.84). However, the GRACE risk score overestimated the absolute in-hospital and 1-year mortality risk (Hosmer-Lemeshow goodness-of-fit test p<0.01). Intermediate-risk and high-risk patients were 12% and 29% less likely to receive optimal guideline-recommended care compared with low-risk patients, respectively. Optimal guideline-recommended care was associated with lower mortality in intermediate- and high-risk patients. CONCLUSIONS: The GRACE risk score identified patients at higher risk for in-hospital and 1-year mortality, but overestimated absolute risk levels in contemporary patients. Optimal guideline-recommended care was associated with lower mortality in intermediate-risk and high-risk patients, but was less likely to be delivered with increasing mortality risk.

Patient-tailored antithrombotic therapy following percutaneous coronary intervention.

Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from either shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y12 inhibitor monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk scores, platelet function testing , and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint on the use of different risk stratification methods alongside clinical judgement in current clinical practice.

Rationale and Design of the Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome (FORCE-ACS) Registry: Towards "Personalized Medicine" in Daily Clinical Practice.

Diagnostic and treatment strategies for acute coronary syndrome have improved dramatically over the past few decades, but mortality and recurrent myocardial infarction rates remain high. An aging population with increasing co-morbidities heralds new clinical challenges. Therefore, in order to evaluate and improve current treatment strategies, detailed information on clinical presentation, treatment and follow-up in real-world patients is needed. The Future Optimal Research and Care Evaluation in patients with Acute Coronary Syndrome (FORCE-ACS) registry (ClinicalTrials.gov Identifier: NCT03823547) is a multi-center, prospective real-world registry of patients admitted with (suspected) acute coronary syndrome. Both non-interventional and interventional cardiac centers in different regions of the Netherlands are currently participating. Patients are treated according to local protocols, enabling the evaluation of different diagnostic and treatment strategies used in daily practice. Data collection is performed using electronic medical records and quality-of-life questionnaires, which are sent 1, 12, 24 and 36 months after initial admission. Major end points are all-cause mortality, myocardial infarction, stent thrombosis, stroke, revascularization and all bleeding requiring medical attention. Invasive therapy, antithrombotic therapy including patient-tailored strategies, such as the use of risk scores, pharmacogenetic guided antiplatelet therapy and patient reported outcome measures are monitored. The FORCE-ACS registry provides insight into numerous aspects of the (quality of) care for acute coronary syndrome patients.

Effect of Adding Ticagrelor to Standard Aspirin on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting (POPular CABG): A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Approximately 15% of saphenous vein grafts (SVGs) occlude during the first year after coronary artery bypass graft surgery (CABG) despite aspirin use. The POPular CABG trial (The Effect of Ticagrelor on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting Surgery) investigated whether ticagrelor added to standard aspirin improves SVG patency at 1 year after CABG. METHODS: In this investigator-initiated, randomized, double-blind, placebo-controlled, multicenter trial, patients with ≥1 SVGs were randomly assigned (1:1) after CABG to ticagrelor or placebo added to standard aspirin (80 mg or 100 mg). The primary outcome was SVG occlusion at 1 year, assessed with coronary computed tomography angiography, in all patients that had primary outcome imaging available. A generalized estimating equation model was used to perform the primary analysis per SVG. The secondary outcome was 1-year SVG failure, which was a composite of SVG occlusion, SVG revascularization, myocardial infarction in myocardial territory supplied by a SVG, or sudden death. RESULTS: Among 499 randomly assigned patients, the mean age was 67.9±8.3 years, 87.1% were male, the indication for CABG was acute coronary syndrome in 31.3%, and 95.2% of procedures used cardiopulmonary bypass. Primary outcome imaging was available in 220 patients in the ticagrelor group and 223 patients in the placebo group. The SVG occlusion rate in the ticagrelor group was 10.5% (51 of 484 SVGs) versus 9.1% in the placebo group (43 of 470 SVGs), odds ratio, 1.29 [95% CI, 0.73-2.30]; P=0.38. SVG failure occurred in 35 (14.2%) patients in the ticagrelor group versus 29 (11.6%) patients in the placebo group (odds ratio, 1.22 [95% CI, 0.72-2.05]). CONCLUSIONS: In this randomized, placebo-controlled trial, the addition of ticagrelor to standard aspirin did not reduce SVG occlusion at 1 year after CABG. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02352402.

Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

BACKGROUND: The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS: In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P = 0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P = 0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, -8.2 percentage points; 95% CI for noninferiority, -14.9 to -1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P = 0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, -0.2 percentage points; 95% CI for noninferiority, -4.7 to 4.3; P = 0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P = 0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS: Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).

Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

BACKGROUND: The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied. METHODS: We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedure-related bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P = 0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P = 0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, -3.9 percentage points; 95% CI for noninferiority, -11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31). CONCLUSIONS: In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).

Comparison of non-triggered magnetic resonance imaging and echocardiography for the assessment of left atrial volume and morphology.

BACKGROUND: Advanced atrial fibrillation (AF) patients have persistent AF, failed previous catheter ablation and/or an enlarged left atrium (LA), which is associated with a reduced success of AF ablation. Transthoracic echocardiography (TTE) and contrast enhanced magnetic resonance angiography (CE-MRA) are available to assess LA volume. However, it is unknown how these modalities relate in patients with advanced AF. We therefore compared the reproducibility of TTE and non-triggered CE-MRA in advanced AF patients and their ability to select patients with successful thoracoscopic AF ablation. METHODS: Two independent observers measured LA volumes on 65 TTE and CE-MRA exams of advanced AF patients prior to AF ablation. Patients were followed after AF ablation with rhythm monitoring every 3 months for 1 year to determine AF recurrence. Inter-modality, inter- and intra-observer variability were determined using intraclass correlation coefficients (ICC). Receiver-operating characteristic (ROC) analysis was performed to determine sensitivity and specificity of TTE and CE-MRA volume and CE-MRA dimensions to identify patients with AF recurrence during follow-up. RESULTS: LA enlargement ≥ 34 ml/m2 was present in 60% of the patients. CE-MRA and TTE demonstrated a good correlation for LA volume assessment (intraclass correlation, ICC = 0.86; p < 0.001) with larger volumes consistently measured by CE-MRA. Major discrepancies were mostly attributed to TTE acquisition. Craniocaudal enlargement discriminated patients with AF recurrence (AUC 0.67 [95% CI 0.55-0.85], p = 0.01). CONCLUSIONS: Non-triggered CE-MRA is a viable and reproducible 3D alternative for 2D TTE to assess LA volume in advanced AF patients. Craniocaudal enlargement was the only discriminator of AF recurrence after AF ablation.

The change in circulating galectin-3 predicts absence of atrial fibrillation after thoracoscopic surgical ablation.

Aims: Galectin-3 (Gal-3) is an important mediator of cardiac fibrosis, particularly in heart failure. Increased Gal-3 concentration (Gal-3), associated with increased risk of developing atrial fibrillation (AF), may reflect atrial fibrotic remodelling underlying AF progression. We aimed to investigate whether the change in serum Gal-3 reflects alterations of the arrhythmogenic atrial substrate following thoracoscopic AF surgery, and predicts absence of AF. Methods and results: Consecutive patients undergoing thoracoscopic AF surgery were included. Left atrial appendages (LAAs) and serum were collected during surgery and serum again 6 months thereafter. Gal-3 was determined in tissue and serum. Interstitial collagen in the LAA was quantified using Picrosirius red staining. Ninety-eight patients (76% male, mean age 60 ± 9 years) underwent thoracoscopic surgery for advanced AF. Patients with increased Gal-3 after ablation compared to baseline had a higher recurrence rate compared to patients with decreased or unchanged Gal-3 (HR 2.91, P = 0.014). These patients more frequently had persistent AF, longer AF duration and thick atrial collagen strands (P = 0.049). At baseline, Gal-3 was similar between patients with and without AF recurrence: 14.8 ± 3.9 µg/L vs. 13.7 ± 3.7 µg/L, respectively in serum (P = 0.16); 94.5 ± 19.4 µg/L vs. 93.3 ± 30.8µg/L, respectively in atrial myocardium (P = 0.83). There was no correlation between serum Gal-3 and left atrial Gal-3 (P = 0.20), nor between serum Gal-3 and the percentage of fibrosis in LAA (P = 0.18). Conclusion: The change of circulating Gal-3, rather than its baseline value, predicts AF recurrence after thoracoscopic ablation. Patients in whom Gal-3 increases after ablation have a high recurrence rate reflecting ongoing profibrotic signalling, irrespective of arrhythmia continuation.

Ganglion Plexus Ablation in Advanced Atrial Fibrillation: The AFACT Study.

BACKGROUND: Patients with long duration of atrial fibrillation (AF), enlarged atria, or failed catheter ablation have advanced AF and may require more extensive treatment than pulmonary vein isolation. OBJECTIVES: The aim of this study was to investigate the efficacy and safety of additional ganglion plexus (GP) ablation in patients undergoing thoracoscopic AF surgery. METHODS: Patients with paroxysmal AF underwent pulmonary vein isolation. Patients with persistent AF also received additional lines (Dallas lesion set). Patients were randomized 1:1 to additional epicardial ablation of the 4 major GPs and Marshall's ligament (GP group) or no extra ablation (control) and followed every 3 months for 1 year. After a 3-month blanking period, all antiarrhythmic drugs were discontinued. RESULTS: Two hundred forty patients with a mean AF duration of 5.7 ± 5.1 years (59% persistent) were included. Mean procedure times were 185 ± 54 min and 168 ± 54 min (p = 0.015) in the GP (n = 117) and control groups (n = 123), respectively. GP ablation abated 100% of evoked vagal responses; these responses remained in 87% of control subjects. Major bleeding occurred in 9 patients (all in the GP group; p < 0.001); 8 patients were managed thoracoscopically, and 1 underwent sternotomy. Sinus node dysfunction occurred in 12 patients in the GP group and 4 control subjects (p = 0.038), and 6 pacemakers were implanted (all in the GP group; p = 0.013). After 1 year, 4 patients had died (all in the GP group, not procedure related; p = 0.055), and 9 were lost to follow-up. Freedom from AF recurrence in the GP and control groups was not statistically different whether patients had paroxysmal or persistent AF. At 1 year, 82% of patients were not taking antiarrhythmic drugs. CONCLUSIONS: GP ablation during thoracoscopic surgery for advanced AF has no detectable effect on AF recurrence but causes more major adverse events, major bleeding, sinus node dysfunction, and pacemaker implantation. (Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery [AFACT]; NCT01091389).