Coronary Vasomotor Dysfunction Is Associated With Cardiovascular Events in Patients With Nonobstructive Coronary Artery Disease.

BACKGROUND: Coronary vasomotor dysfunction (CVDys) can be comprehensively classified on the basis of anatomy and functional mechanisms. OBJECTIVES: The aim of this study was to evaluate the association between different CVDys phenotypes and outcomes in patients with angina and nonobstructive coronary artery disease (ANOCA). METHODS: Patients with ANOCA who underwent coronary reactivity testing using an intracoronary Doppler guidewire to assess microvascular and epicardial coronary endothelium-dependent and endothelium-independent function were enrolled. Endothelium-dependent microvascular and epicardial coronary dysfunction were defined as a <50% change in coronary blood flow in response to intracoronary acetylcholine (Ach) infusion and a <-20% change in coronary artery diameter in response to Ach. Endothelium-independent microvascular and epicardial coronary dysfunction were defined as coronary flow reserve < 2.5 during adenosine-induced hyperemia and change in cross-sectional area in response to intracoronary nitroglycerin administration < 20%. Major adverse cardiac and cerebrovascular events (cardiovascular death, nonfatal MI, heart failure, stroke, and late revascularization) served as clinical outcomes. RESULTS: Among the 1,196 patients with ANOCA, the prevalence of CVDys was 24.5% and 51.8% among those with endothelium-independent and endothelium-dependent microvascular dysfunction, respectively, and 47.4% and 25.4% among those with endothelium-independent and endothelium-dependent epicardial coronary dysfunction, respectively. During 6.3 years (Q1-Q3: 2.5-12.9 years) of follow-up, patients with endothelium-dependent microvascular dysfunction, endothelium-dependent epicardial coronary dysfunction, or endothelium-independent microvascular dysfunction showed significantly higher event rates compared with those without (19.5% vs 12.0% [P < 0.001], 19.7% vs 14.6% [P = 0.038] and 22.2% vs 13.8% [P = 0.001], respectively). Coronary flow reserve (HR: 0.757; 95% CI: 0.604-0.957) and percentage change in coronary blood flow in response to Ach infusion (HR: 0.998; 95% CI: 0.996-0.999) remained significant predictors of major adverse cardiac and cerebrovascular event after adjustment for conventional risk factors. CONCLUSIONS: CVDys phenotype is differentially associated with worse outcomes, and endothelium-dependent and endothelium-independent microvascular function provide independent prognostic information in patients with ANOCA.

Noninvasive transthoracic doppler flow velocity and invasive thermodilution to assess coronary flow reserve.

Background: Coronary flow reserve (CFR) provides prognostication and coronary physiological information, including epicardial coronary stenosis and microvascular function. The relationship between stress transthoracic Doppler echocardiography (TDE)-derived coronary flow velocity reserve (CFRS-TDE) and thermodilution-derived coronary flow reserve (CFRthermo) before and after elective percutaneous coronary intervention (PCI) remains unclear. Methods: This single-center prospective registry study evaluated patients who underwent fractional flow reserve (FFR)-guided elective PCI for left anterior descending artery (LAD) lesions with wire-based invasive physiological measurements and pre- and post-PCI stress TDE examinations. Results: A total of 174 LAD lesions from 174 patients were included in the final analysis. A modest correlation was detected between the pre-PCI CFRS-TDE and the pre-PCI CFRthermo (r=0.383, P<0.001). The frequently used CFRS-TDE threshold of 2.0 corresponded to a pre-PCI CFRthermo of 2.18. Pre-PCI CFRS-TDE underestimated pre-PCI CFRthermo [1.89 (1.44-2.31) vs. 2.05 (1.38-2.93), P<0.001]. Both CFRS-TDE and CFRthermo increased significantly post-PCI [pre-PCI CFRS-TDE 1.89 vs. post-PCI CFRS-TDE 2.33, P<0.001; pre-PCI CFRthermo 2.05 (1.38-2.93) vs. post-PCI CFRthermo 2.59 (1.63-3.55), P<0.001]. In contrast, there was no significant relationship between changes in CFRS-TDE and changes in CFRthermo after PCI (r=0.008, P=0.915) or between post-PCI CFRS-TDE and post-PCI CFRthermo (r=0.054, P=0.482). Conclusions: Pre-PCI CFRS-TDE and CFRthermo are modestly correlated, but post-PCI CFRS-TDE and CFRthermo have no correlation. CFRS-TDE and CFRthermo are not interchangeable, particularly post-PCI, suggesting that the two metrics represent different coronary physiologies after PCI.

Diagnostic value of computed tomography myocardial perfusion imaging to detect coexisting microvascular dysfunction in patients with obstructive epicardial coronary artery disease.

Background: Computed tomography myocardial perfusion (CT-MP) has reported usefulness in assessing hemodynamically significant epicardial coronary artery lesions. However, the diagnostic ability of the absolute coronary flow using CT-MP to detect coronary microvascular dysfunction (CMD) remains elusive. This prospective cohort study aimed to assess the diagnostic value of CT-MP in evaluating coexisting CMD in patients with functionally significant epicardial coronary stenosis and to analyze the predictive factors of lesions with CMD. Methods: Sixty-eight patients with chronic coronary syndrome (CCS) and de novo single functionally significant stenosis [fractional flow reserve (FFR) ≤0.80] were studied. CMD was defined as an index of microcirculatory resistance ≥25. We compare clinical background and CT-MP findings between patients with and without CMD (CMD, n=29; non-CMD, n=39). CT-MP, and quantitative and qualitative plaque assessments were included in computed tomography angiography assessment. Logistic regression analysis was performed to predict CMD. Results: FFR, invasive wire-derived coronary flow reserve (CFRwire) and index of microcirculatory resistance were 0.68 [interquartile range (IQR), 0.59-0.74], 1.71 (IQR, 1.24-2.88), and 22.6 (IQR, 15.1-34.5), respectively. The rest and hyperemic-myocardial blood flow (MBF) and CT-MP-derived CFR (CFRCT-MP) were 0.83 (0.64-1.03) mL/min/g, 2.14 (1.30-2.92) mL/min/g, and 2.19 (1.44-3.37), respectively. In the territories with CMD, hyperemic-MBF was significantly lower than in those without [1.68 (IQR, 0.84-2.44) vs. 2.31 (IQR, 1.67-3.34) mL/min/g, P=0.015] and the prevalence of CFRCT-MP <2.0 was higher in the lesions with CMD than in those without (62.1% vs. 28.2%, P=0.011), while FFR values were similar. Fibrofatty and necrotic core component volume was greater in the vessels with CMD than in those without [31.8 (IQR, 19.0-48.9) vs. 25.1 (IQR, 17.2-32.1) mm3, P=0.045]. Multivariable logistic regression analysis showed that hyperemic-MBF and fibrofatty and necrotic core component volume were independent predictors of CMD territories [odds ratio (OR) =0.583; 95% confidence interval (CI): 0.355-0.958; P=0.033 and OR =1.040; 95% CI: 1.010-1.070; P=0.011]. Conclusions: Quantitative assessment of absolute coronary flow using pre-percutaneous coronary intervention (PCI) CT-MP, and comprehensive plaque analysis using computed tomography angiography may help detect coexisting subtended microvascular dysfunction in territories with functionally significant epicardial coronary lesions. Further studies are required to elucidate the clinical significance of coexisting CMD in patients with CCS undergoing PCI.

Age-related changes in the coronary microcirculation influencing the diagnostic performance of invasive pressure-based indices and long-term patient prognosis.

OBJECTIVES: Investigate age-related changes in coronary microvascular function, its effect on hyperemic and non-hyperemic indices of stenosis relevance, and its prognostic implications. BACKGROUND: Evidence assessing the effect of age on fractional flow reserve (FFR), resting mean distal intracoronary pressure/mean aortic pressure (Pd/Pa), and microcirculatory function remains scarce. METHODS: This is a post hoc study of a large prospective international registry (NCT03690713) including 1134 patients (1326 vessels) with coronary stenoses interrogated with pressure and flow guidewires. Age-dependent correlations with functional indices were analyzed. Prevalences of FFR, resting Pd/Pa, and coronary flow reserve (CFR) classification agreement were assessed. At 5 years follow-up, the relation between resting Pd/Pa, CFR, and their age-dependent implications on FFR-guided percutaneous coronary intervention (PCI) deferral (deferred if FFR > 0.80) were investigated using vessel-oriented composite outcomes (VOCO) composed of death, myocardial infarction, and repeated revascularization. RESULTS: Age correlated positively with FFR (r = 0.08, 95% confidence interval [CI]: 0.03 to 0.13, p = 0.005), but not with resting Pd/Pa (r = -0.03, 95% CI:-0.09 to 0.02, p = 0.242). CFR correlated negatively with age (r = -0.15, 95% CI: -0.21 to -0.10, p < 0.001) due to a significant decrease in maximal hyperemic flow in older patients. Patients over 60 years of age with FFR-guided deferred-PCI abnormal resting Pd/Pa or abnormal CFR had increased risk of VOCO (hazard ratio [HR]: 2.10, 95% CI: 1.15 to 4.36, p = 0.048; HR: 2.46, 95% CI:1.23 to 4.96, p = 0.011; respectively). CONLUSIONS: Aging is associated with decrease in microcirculatory vasodilation, as assessed with adenosine-based methods like CFR. In patients older than 60 years in whom PCI is deferred according to FFR > 0.80, CFR and resting Pd/Pa have an incremental value in predicting future vessel-oriented patient outcomes.

Prognostic Value of Coronary Sinus Flow Quantification by Cardiac Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction.

Background This study aimed to evaluate the prognostic value of hyperemic coronary sinus flow (h-CSF) and global coronary flow reserve (g-CFR) obtained by phase-contrast cine-magnetic resonance imaging in patients with acute myocardial infarction (MI). Methods and Results This retrospective study analyzed patients with acute MI (n=523) who underwent primary (ST-segment-elevation MI) or urgent (non-ST-segment-elevation MI) percutaneous coronary intervention. Absolute coronary sinus blood flow (CSF) at rest and during vasodilator stress hyperemia was quantified at 30 days (24-36 days) after the index infarct-related lesion percutaneous coronary intervention and revascularization of functionally significant non-infarct-related lesions. We used Cox proportional hazards regression modeling to examine the association between h-CSF, g-CFR, and major adverse cardiac events defined as all-cause death, nonfatal MI, hospitalization for congestive heart failure, and stroke. Finally, 325 patients with ST-segment-elevation MI (62.1%) and 198 patients with non-ST-segment-elevation MI (37.9%) were studied over a median follow-up of 2.5 years. The rest CSF, h-CSF, and g-CFR were 0.94 (0.68-1.26) mL/min per g, 2.05 (1.42-2.73) mL/min per g, and 2.17 (1.54-3.03), respectively. Major adverse cardiac events occurred in 62 patients, and Cox proportional hazards analysis showed that h-CSF and g-CFR were independent predictors of major adverse cardiac events (h-CSF: hazard ratio [HR], 0.64; 95% CI, 0.47-0.88; P=0.005; g-CFR: HR, 0.62; 95% CI, 0.47-0.82; P=0.001). When stratified by h-CSF and g-CFR, cardiac event-free survival was the worst in patients with concordantly impaired h-CSF (<1.6 mL/min per g) and g-CFR (<1.7) (P<0.001). Conclusions Global coronary sinus flow quantification using phase-contrast cine-magnetic resonance imaging provided significant prognostic information independent of infarction size and conventional risk factors in patients with acute MI undergoing revascularization.

Clinical determinants of coronary artery disease burden and vulnerability using optical coherence tomography co-registered with intravascular ultrasound.

OBJECTIVES: We investigated clinical determinants of disease burden and vulnerability using optical coherence tomography (OCT) co-registered with intravascular ultrasound (IVUS) in a large cohort of patients. METHODS: A total of 704 patients [44.5% with acute coronary syndromes (ACS)] underwent coronary intervention. IVUS plaque burden and OCT lipid, macrophage and calcium indices and the presence of thrombus, plaque rupture and thin-cap fibroatheroma (TCFA) were analyzed. RESULTS: Median patient age was 66 years with 81.8% men, 34.4% with diabetes mellitus and 15.5% with preadmission statins. Median lesion length was 25.7 mm, and 33.0% had a TCFA. Adjusted models indicated (1) older patient age was related to more calcium, but fewer macrophages; (2) men were related to more thrombus with plaque rupture while women had more thrombus without plaque rupture; (3) ACS presentation was related to morphological acute thrombotic events (more thrombus with/without rupture) and plaque vulnerability (more TCFA, more lipid and macrophages and larger plaque burden); (4) diabetes mellitus was related to a greater atherosclerotic disease burden (more lipid and calcium and larger plaque burden) and more thrombus without rupture; (5) hypertension was related to more macrophages; (6) current smoking was related to less calcium; and (7) renal insufficiency and preadmission statin therapy were not independently associated with IVUS or OCT plaque morphology. CONCLUSION: Patient characteristics, especially diabetes mellitus and aging, affect underlying atherosclerotic burden, among which a greater lipidic burden along with sex differences influence local thrombotic morphology that affects clinical presentation.

Effect of percutaneous coronary intervention on global hemodynamics and the prevalence of residual microvascular dysfunction.

OBJECTIVES: We aimed to examine the changes in hyperemic coronary sinus flow (CSF) and global coronary flow reserve (g-CFR) after percutaneous coronary intervention (PCI) and investigate the predictors to improve these metrics and the prevalence of residual coronary microvascular dysfunction (CMD). METHODS: This prospective, single-center study included 118 patients with stable coronary artery disease undergoing PCI for a single proximal lesion. Phase-contrast cine-cardiac magnetic resonance (PC-CMR) was used to assess hyperemic CSF (HCSF) and g-CFR, before and after PCI. Residual CMD was defined as concordantly impaired post-PCI HCSF (<2.3 ml/min/g) and g-CFR (<2.0). RESULTS: HCSF significantly increased, although 38 (32.2%) patients showed a decrease. There was no significant change in g-CFR despite fractional flow reserve (FFR) improvement in all target territories. Concordantly increased HCSF and g-CFR were effectively discriminated by adding PC-CMR-derived information to pre-PCI FFR. Residual CMD was observed in 30 (25.4%) patients and was associated with pre-PCI renal dysfunction and lower pre-PCI rest and hyperemic CSF, but not with pre-PCI regional physiological indices. CONCLUSIONS: FFR-guided PCI was associated with increased HCSF, but not with increased g-CFR. After uncomplicated PCI, one-quarter of patients showed residual CMD. Our approach may help identify patients who may benefit from increased coronary perfusion or show residual CMD.

Association between pericoronary adipose tissue attenuation and outcome after second-generation cryoballoon ablation for atrial fibrillation.

OBJECTIVES: Previous studies reported the association between inflammation and atrial fibrillation (AF). Pericoronary adipose tissue (PCAT) attenuation, PCATA, on cardiac CT angiography (CTA) reflects pericoronary inflammation. We hypothesized that the PCATA predicts AF recurrence after cryoballoon ablation (CBA) for paroxysmal and persistent AF. METHODS: We studied 364 patients (median age, 65 years) with persistent (n = 41) and paroxysmal (n = 323) AF undergoing successful first-session second-generation CBA with pre-ablation cardiac CTA. Three-vessel (3V)-PCATA was defined as the mean CT attenuation value of PCAT of all three major coronary arteries. Predictors of AF recurrence during follow-up were evaluated. RESULTS: AF recurrence after the 3-month blanking period was detected in 90 patients (24.7%) during the median follow-up of 26 (interquartile range, 19-42) months. AF recurrence was associated with prior stroke and statin use, NT-proBNP and high-sensitivity cardiac troponin-I levels, left ventricular dimension, left atrial volume index (LAVI), 3V-PCATA, and early AF recurrence during the blanking period. On multivariable Cox proportional hazard analysis, prior stroke (hazard ratio [HR], 2.208, 95% confidence interval [CI], 1.166-4.180, p = 0.015), LAVI (HR, 1.030, 95% CI, 1.010-1.051, p = 0.003), 3V-PCATA (HR, 1.034, 95% CI, 1.001-1.069, p = 0.046), and early AF recurrence (HR, 2.858, 95% CI, 1.855-4.405, p < 0.001) remained statistically significant. CONCLUSION: Pre-ablation CTA-derived 3V-PCATA, representing pericoronary inflammation, was an independent predictor of recurrence after first-session AF ablation using a second-generation cryoballoon. ADVANCES IN KNOWLEDGE: Assessment of 3V-PCATA may identify patients at high risk of AF recurrence after CBA for AF.

Effect of contrast medium versus low-molecular-weight dextran for intracoronary optical coherence tomography in renal insufficiency.

Low-molecular-weight dextran (LMWD) is considered a safe alternative to contrast media to displace blood during optical coherence tomography (OCT) imaging, but concerns remain. The purpose of this study was to investigate whether using LMWD for OCT protects against kidney injury in patients with renal insufficiency compared with contrast media. We retrospectively identified 474 patients with renal insufficiency (estimated glomerular filtration rate < 60 ml/min/1.73 m2) who underwent OCT during coronary angiography or percutaneous coronary intervention; 110 patients with LMWD plus contrast medium (LMWD group) and 364 patients with contrast medium exclusively (Contrast group). We evaluated differences between the two groups and performed propensity score-matched subgroup comparisons. Compared with the Contrast group, the LMWD group had worse baseline renal function, higher prevalence of diabetes mellitus and percutaneous coronary intervention history, higher C-reactive protein and N-terminal pro B-type natriuretic peptide levels, lower hemoglobin levels, and lower left ventricular ejection fraction. The median total volume of contrast medium in the Contrast group was 230.0 ml vs. 61.8 ml of LMWD in addition to 164.0 ml of contrast medium in the LMWD group. Renal function was consistently impaired in the LMWD group within 5 days, at 1-month, and 1-year follow-up (P < 0.001). Two propensity score-matched analyses adjusted for either total volume used or contrast media volume consistently indicated a trend toward worsening renal function in the LMWD group at the 1-year follow-up. No protective benefit for renal function from using LMWD instead of contrast media for OCT was observed in patients with renal insufficiency.

Prognostic Impact of Residual Anatomic Disease Burden After Functionally Complete Revascularization.

BACKGROUND: Prognostic impact of residual anatomic disease burden after functionally complete percutaneous coronary intervention (PCI), defined by post-PCI fractional flow reserve (FFR) >0.80 would be a clinically relevant question. The current study evaluated clinical outcomes at 2 years according to residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (RSS) in patients who underwent functionally complete revascularization. METHODS: A total of 1910 patients (2095 revascularized vessels) with post-PCI FFR >0.80 were selected from the International Post-PCI FFR Registry. RSS was defined as the SYNTAX score recalculated after PCI, SYNTAX revascularization index was calculated as 100×(1-RSS/pre-PCI SYNTAX score), and post-PCI FFR was measured after completion of PCI. The primary outcome was target vessel failure (TVF; a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization) at 2 years, and risk of TVF was compared according to tertile classification of RSS (0, 1-5, and >5) and post-PCI FFR (≥0.94, 0.87-0.93, and ≤0.86). RESULTS: After PCI, SYNTAX score was changed from 10.0 (Q1-Q3, 7.0-16.0) to 0.0 (Q1-Q3, 0.0-5.0) and FFR changed from 0.70±0.12 to 0.90±0.05. TVF at 2 years occurred in 4.9%, and patients with TVF showed higher pre-PCI SYNTAX score and lower post-PCI FFR than those without. However, there were no significant differences in SYNTAX revascularization index and RSS. The risk of TVF was not different according to tertile of RSS (log-rank P=0.851). Conversely, risk of TVF was different according to tertile of post-PCI FFR (log-rank P=0.009). Multivariable model showed the risk of TVF was significantly associated with post-PCI FFR (hazard ratio, 1.091 [95% CI, 1.032-1.153]; P=0.002) but not with RSS (hazard ratio, 0.969 [95% CI, 0.898-1.045]; P=0.417). CONCLUSIONS: Among patients who underwent functionally complete revascularization, residual anatomic disease burden assessed by RSS was not related with occurrence of TVF at 2 years. These results support the importance of functionally complete revascularization rather than angiographic complete revascularization. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04012281.

Clinical significance of the presence of puff-chandelier ruptures detected by nonobstructive aortic angioscopy.

OBJECTIVE: This study aimed to investigate the prevalence and prognostic significance of atherosclerotic aortic plaques (AAPs) or specific AAP types detected by nonobstructive angioscopy (NOA) in patients who underwent percutaneous coronary intervention (PCI). BACKGROUND: Although recent studies have reported the presence of various patterns of AAPs, identified by NOA, the clinical significance of the presence of AAPs remains elusive. METHODS: In this retrospective, multicenter cohort study, a total of 167 patients who underwent PCI and intra-aortic scans with NOA were studied. The association between AAPs and the incidence of major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, stroke, and clinically driven unplanned revascularizations, was assessed. RESULTS: AAPs were detected in 126 patients (75%) who underwent NOA. MACEs occurred in 28 (17%) patients during the follow-up (median 2.9 years [range 2.1-3.8]). Among all types of AAPs, only puff-chandelier rupture (PCR) showed a significant difference in frequency between patients with and those without MACEs: 21 (75%) and 49 (35%), respectively (p < .001). Multivariable Cox proportional hazard analysis revealed that PCR (hazard ratio [HR] 3.73, 95% confidence interval [CI] 1.57-8.87, p = .004) and chronic kidney disease (HR 2.97, 95% CI 1.37-6.44, p = .010) were independent predictors of MACEs. Kaplan-Meier analysis revealed that PCR was significantly associated with more frequent MACEs. CONCLUSION: The detection of PCR in the aorta using NOA was significantly associated with an increased risk of subsequent adverse events after PCI.

Recurrence after "long-term success" in catheter ablation of paroxysmal atrial fibrillation.

BACKGROUND: The latest guidelines define "long-term success" as freedom from atrial arrhythmia recurrence more than 36 months after procedures without any antiarrhythmic drug therapy. OBJECTIVE: The purpose of this study was to investigate the clinical outcomes and procedural findings in patients with recurrence beyond "long-term success." METHODS: Among patients who underwent pulmonary vein (PV) antrum isolation for drug-refractory symptomatic paroxysmal atrial fibrillation (AF), 37 in whom recurrent arrhythmias were observed during annual follow-up after "long-term success" and who underwent repeat procedures for recurrent arrhythmias were included in the study. RESULTS: The time from the latest procedure to recurrence was a median of 61 ([25th, 75th percentiles]: [51-77.5]) months. Recurrent arrhythmia type was paroxysmal in 22 patients (59.5%) and persistent in 15 (40.5%). Recurrent arrhythmias were atrial tachycardia (AT) in 13 patients (35.1%), including 8 with AT unrelated to PVs. Repeat procedures were performed a median of 2.0 [1.0-4.0] months after identifying recurrent episodes. Recovered PV conduction was found in 29 patients (78.4%) and non-PV foci in 4 (10.8%). Freedom from recurrence 1 year after repeat procedures was 63.3%. Seven patients (18.9%) underwent further repeat procedures a median of 7.0 [2.0-28.0] months after repeat procedures and had no PV reconnections. In total, AF/AT unrelated to PVs was present in 24 patients (64.9%). In contrast, arrhythmias related to PVs were observed in 2 patients (5.4%) during a total of 46 repeat procedures after "long-term success." CONCLUSION: Although PV reconnections were commonly found even after "long-term success," AF/AT unrelated to PVs was assumed to be present in the majority of this population.

Adenosine-Provoked Atrial Fibrillation Originating From Non-Pulmonary Vein Foci: The Clinical Significance and Outcome After Catheter Ablation.

OBJECTIVES: The goal of this study was to systematically investigate the incidence and clinical significance of non-pulmonary vein (PV) foci revealed by adenosine/adenosine triphosphate (ATP) testing during atrial fibrillation (AF) ablation. BACKGROUND: ATP is reported to provoke AF. METHODS: A total of 464 patients with consecutive paroxysmal AF undergoing ATP testing after PV antrum isolation were included. RESULTS: AF originating from non-PV foci was provoked in 26 (5.6%) total patients during first (n = 20) or repeat (n = 8) ablation procedures. Dormant PV conduction was also revealed by ATP testing in 6 patients. Non-PV foci were located in the superior vena cava (SVC) (i.e., the SVC group) and atria (i.e., the atria group) in 10 and 18 (9 each in the right and left atria) patients, respectively. In the multivariable analysis, being female was the sole independent predictor of ATP-provoked AF originating from non-PV foci (hazard ratio [HR]: 2.52 [95% confidence interval (CI): 1.069 to 5.929]; p = 0.034). After additional ablation targeting non-PV foci, freedom from recurrent AF after the last procedure was similar between the SVC group and patients without ATP-provoked AF but was significantly lower in the atria group than in others (p = 0.0008). Atria group membership (HR: 3.725 [95% CI: 1.692 to 8.199]; p = 0.001) and being female (HR: 1.538 [95% CI: 1.189 to 1.989]; p = 0.001) were significant independent predictors associated with recurrence after the last procedure in the multivariable Cox regression model. CONCLUSIONS: ATP provoked AF originating from non-PV foci under isoproterenol in 5.6% of patients undergoing paroxysmal AF ablation. ATP testing might be useful for identifying and eliminating AF originating from the SVC. The atria group was associated with a poor outcome after the last procedure despite efforts to eliminate non-PV foci.