RESUMEN
AIMS: Late gadolinium enhancement cardiac magnetic resonance (CMR) permits characterization of left ventricular ischaemic scars. We aimed to evaluate if scar core mass, border zone (BZ) mass, and BZ channels are risk markers for subsequent ventricular arrhythmia (VA) in ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: A sub-study of the DANish Acute Myocardial Infarction-3 multi-centre trial and Danegaptide phase II proof-of-concept clinical trial in which a total of 843 STEMI patients had a 3-month follow-up CMR. Of these, 21 patients subsequently experienced VA during 100 months of follow-up and were randomly matched 1:5 with 105 controls. A VA event was defined as: ventricular tachycardia, ventricular fibrillation, or sudden cardiac death. Ischaemic scar characteristics were automatically detected by specialized software. We included 126 patients with a median left ventricular ejection fraction of 51.0 ± 11.6% in cases with VA vs. 55.5 ± 8.5% in controls (P = 0.10). Cases had a larger mean BZ mass and more often BZ channels compared to controls [BZ mass: 17.2 ± 10.3 g vs. 10.3 ± 6.0 g; P = 0.0002; BZ channels: 17 (80%) vs. 44 (42%); P = 0.001]. A combination of ≥17.2 g BZ mass and the presence of BZ channels was five times more prevalent in cases vs. controls (P ≤ 0.00001) with an odds ratio of 9.40 (95% confidence interval 3.26-27.13; P ≤ 0.0001) for VA. This identified cases with 52% sensitivity and 90% specificity. CONCLUSION(S): Scar characterization with CMR indicates that a combination of ≥17.2 g BZ mass and the presence of BZ channels had the strongest association with subsequent VA in STEMI patients. CLINICALTRIALS.GOV: Unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER), NCT01960933 (DANAMI 3-PRIMULTI), and NCT01977755 (Danegaptide).
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Infarto del Miocardio , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Cicatriz/etiología , Cicatriz/complicaciones , Volumen Sistólico , Medios de Contraste , Función Ventricular Izquierda , Gadolinio , Imagen por Resonancia Magnética/métodos , Arritmias Cardíacas/complicaciones , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico por imagen , Imagen por Resonancia Cinemagnética/métodosRESUMEN
OBJECTIVES: Acute STEMI is routinely treated by acute PCI. This treatment may itself damage the tissue (reperfusion injury). Conditioning with GLP-1 analogs has been shown to reduce reperfusion injury. Likewise, ischemic postconditioning provides cardioprotection following STEMI. We tested if combined conditioning with the GLP-1 analog liraglutide and ischemic postconditioning offered additive cardioprotective effect after reperfusion of 45 min coronary occlusion of left anterior descending artery (LAD). DESIGN: Fifty-eight non-diabetic female Danish Landrace pigs (60 ± 10kg) were randomly assigned to four groups. Myocardial infarction (MI) was induced by occluding the LAD for 45 min. Group 1 (n = 14) was treated with i.v. liraglutide after 15 min of ischemia. Group 2 (n = 17) received liraglutide treatment concomitant with ischemic postconditioning, after 45 min of ischemia. Group 3 (n = 15) recieved ischemic postconditioning and group 4 (n = 12) was kept as controls. RESULTS: No intergroup differences in relative infarct size were detected (overall mean 57 ± 3%; p = 0.68). Overall mortality was 34% (CI 25-41%) including 26% post-intervention, with no intergroup differences (p = 0.99). Occurrence of ventricular fibrillation (VF) was 59% (CI 25-80%) including 39% postintervention with no intergroup differences (p = 0.65). CONCLUSIONS: In our closed-chest pig-model, we were unable to detect any cardioprotective effect of liraglutide or ischemic postconditioning either alone or combined.
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Oclusión con Balón , Incretinas/farmacología , Poscondicionamiento Isquémico/métodos , Liraglutida/farmacología , Infarto del Miocardio/terapia , Miocardio/patología , Intervención Coronaria Percutánea/efectos adversos , Daño por Reperfusión/prevención & control , Animales , Terapia Combinada , Modelos Animales de Enfermedad , Femenino , Poscondicionamiento Isquémico/efectos adversos , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Porcinos , Fibrilación Ventricular/etiologíaRESUMEN
OBJECTIVE: Patients with diabetes are at increased risk of experiencing myocardial infarction. The influence of the prevailing plasma glucose level on infarction and mortality after acute ischaemia is however unknown. The aim was to study the effect of the acute plasma glucose level on the myocardial infarction size in a closed-chest pig model. DESIGN: 38 non-diabetic pigs were randomised to hypoglycaemic (1.8-2.2 mmol/l; n = 15), normoglycaemic (5-7 mmol/l; n = 12) or hyperglycaemic glucose clamping (22-23 mmol/l; n = 11). After 30 min within glucose target myocardial infarction was induced for 30 min followed by reperfusion for 120 min. Hereafter the heart was double-stained to delineate infarction from viable tissue within the area at risk. RESULTS: Mean infarction size was 201 ± 35 mm(2) (mean ± SEM) in the hypoglycaemic group, 154 ± 40 mm(2) in the normoglycaemic group and 134 ± 40 mm(2) in the hyperglycaemic group, with no differences in infarction size, infarct/area at risk ratio or troponin T levels between the groups. There was no difference in incidence of ventricular fibrillation or mortality between the groups. CONCLUSION: No statistically significant associations were observed between the acute glycaemic level and measures of myocardial infarction, rates of ventricular fibrillation and subsequent premature death in the setting of acute ischaemia and reperfusion.
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Glucemia/metabolismo , Hiperglucemia/sangre , Hipoglucemia/sangre , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Animales , Biomarcadores/sangre , Modelos Animales de Enfermedad , Femenino , Hiperglucemia/patología , Hipoglucemia/patología , Infarto del Miocardio/sangre , Infarto del Miocardio/fisiopatología , Daño por Reperfusión Miocárdica/sangre , Daño por Reperfusión Miocárdica/fisiopatología , Factores de Riesgo , Porcinos , Factores de Tiempo , Fibrilación Ventricular/sangre , Fibrilación Ventricular/patología , Fibrilación Ventricular/fisiopatologíaRESUMEN
The concept that the culprit lesion in non-ST segment elevation myocardial infarction (NSTEMI) is caused by sudden plaque rupture with acute thrombus formation has recently been challenged. While angiography is an old gold-standard for culprit identification it merely visualizes the lumen contour. Optical coherence tomography (OCT) provides a detailed view of culprit features. Combined with myocardial edema on cardiac magnetic resonance (CMR), indicating acute ischemia and thus culprit location, we aimed to characterize culprit lesions using OCT. Patients with NSTEMI referred for angiography were prospectively enrolled. OCT was performed on angiographic stenoses ≥50% and on operator-suspected culprit lesions. Hierarchical OCT-culprit identifiers were defined in case of multiple unstable lesions, including OCT-defined thrombus age. An OCT-based definition of an organizing thrombus as corresponding to histological early healing stage was introduced. Lesions were classified as OCT-culprit or non-culprit, and characteristics compared. CMR was performed in a subset of patients. We included 65 patients with 97 lesions, of which 49 patients (75%) had 53 (54%) OCT-culprit lesions. The most common OCT-culprit identifiers were the presence of acute (66%) and organizing thrombus (19%). Plaque rupture was visible in 45% of OCT-culprit lesions. CMR performed in 38 patients revealed myocardial oedema in the corresponding territories of 67% of acute thrombi and 50% of organizing thrombi. A culprit lesion was identified by OCT in 75% patients with NSTEMI. Acute thrombus was the most frequent feature followed by organizing thrombus. Applying specific OCT-criteria to identify the culprit could prove valuable in ambiguous cases.
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Infarto del Miocardio sin Elevación del ST , Placa Aterosclerótica , Infarto del Miocardio con Elevación del ST , Trombosis , Humanos , Infarto del Miocardio sin Elevación del ST/diagnóstico por imagen , Infarto del Miocardio sin Elevación del ST/terapia , Infarto del Miocardio sin Elevación del ST/patología , Tomografía de Coherencia Óptica , Angiografía Coronaria , Valor Predictivo de las Pruebas , Trombosis/patología , Placa Aterosclerótica/patología , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/etiología , Infarto del Miocardio con Elevación del ST/terapia , Rotura/patología , Imagen por Resonancia Magnética , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patologíaRESUMEN
Importance: The neutrophil-lymphocyte ratio (NLR) independently predicts atherosclerotic events and is a potential biomarker for residual inflammatory risk. Interleukin (IL) 1ß inhibition reduces the NLR, but whether inhibition of IL-6, a cytokine downstream of IL-1, also lowers the NLR is uncertain. Objective: To evaluate whether ziltivekimab, a therapeutic monoclonal antibody targeting the IL-6 ligand, associates with a lower NLR compared with placebo. Design, Setting, and Participants: This was an exploratory post hoc analysis of Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition (RESCUE), a double-blind, randomized, placebo-controlled, phase 2 trial conducted from June 17, 2019, to January 14, 2020, with 24 weeks of follow-up. Participants were enrolled at 40 sites in the US and included adults aged 18 or older with moderate to severe chronic kidney disease and high-sensitivity C-reactive protein levels of 2 mg/L or greater. Data were analyzed from September 28, 2021, to October 2, 2022. Interventions: Participants were randomly assigned equally to placebo or ziltivekimab, 7.5 mg, 15 mg, or 30 mg, subcutaneously every 4 weeks. Main Outcomes and Measures: The primary outcome was the change in the NLR at 12 weeks. Results: A total of 264 participants (median [IQR] age, 68 [60-75] years; 135 men [51%]; 129 women [49%]) were enrolled, of which 187 (71%) had diabetes, and 126 (48%) had known atherosclerosis. The median (IQR) change in the NLR at 12 weeks was 1.56% (IQR, -15.7% to 20.0%), -13.5% (IQR, -31.6% to 3.20%), -14.3% (IQR, -26.9% to 4.62%), and -22.4% (IQR, -33.3% to -4.27%) in the placebo, 7.5-mg, 15-mg, and 30-mg groups, respectively. The estimated treatment difference compared with placebo was -14.6% (95% CI, -24.8% to -4.81%; P = .004), -15.3% (95% CI, -25.2% to -5.10%; P = .004), and -23.6% (95% CI, -33.2% to -14.2%; P < .001) in the 7.5-mg, 15-mg, and 30-mg groups, respectively. A similar reduction in the absolute neutrophil count was observed. Conclusions and Relevance: Results of this post hoc analysis of the RESCUE trial show that IL-6 ligand inhibition with ziltivekimab associates with a lower NLR, suggesting that it may disrupt multiple atherogenic inflammatory pathways, including those mediated by the myeloid cell compartment. The NLR may have use in monitoring ziltivekimab's efficacy should it be introduced into clinical practice.
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Aterosclerosis , Interleucina-6 , Adulto , Masculino , Humanos , Femenino , Anciano , Neutrófilos , Ligandos , LinfocitosRESUMEN
Mounting evidence shows that right ventricle (RV) function carries independent prognostic influence in various disease states. This study aimed to investigate the incidence and impact of permanent RV infarction in patients with inferior ST-segment elevation myocardial infarction (STEMI) and culprit lesion in the right coronary artery (RCA). In this substudy of the DANAMI-3 (DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction) trial, cardiac magnetic resonance was performed in 291 patients at day 1 and follow-up 3 months after primary percutaneous coronary intervention of 674 patients with STEMI with the culprit lesion in the RCA. Final infarct was assessed using late gadolinium enhancement on cardiac magnetic resonance at 3 months. Patients with permanent RV infarction (20%) had lower ventricular function at follow-up; RV ejection fraction (EF) 47% ±6 versus 50% ± 5 (p <0.005) and left ventricular (LV) EF 56% ± 8 versus 60% ± 9 (p <0.006). Furthermore, patients with permanent RV infarction had a higher incidence of microvascular obstruction 39 (67%) versus 81 (39%) (p <0.001), larger final LV infarct size 16% ±8 versus 10% ± 8 (p <0.001) and larger LV area at risk 33% ± 10 versus 29% ± 9 (p <0.001). Permanent RV infarction was an independent predictor of final LV infarct size (p <0.001) but was not associated with LVEF (ß = -0.0; p = 0.13) in multivariable analyses. In conclusion, permanent RV infarction was seen in 20% of patients with inferior STEMI and culprit lesion in RCA and independently predicted final LV infarct size. However, permanent RV infarction did not predict overall LV function. LGE was used to detect infarct location and quantify infarct size.17 LGE in RV free wall on follow-up CMR was considered as permanent infarction. LGE images were obtained 10 minutes after intravenous injection of 0.1-mmol/kg body weight of gadolinium-based contrast (Gadovist; Bayer Schering, Berlin, Germany) using an electrocardiogram (ECG)-triggered inversion-recovery sequence. The inversion time was adjusted to null the signal from the normal myocardium. Short-axis images were acquired from the atrioventricular plane to the apex with adjacent 8-mm slices. The remaining protocol has been described previously.16.
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/epidemiología , Gadolinio , Medios de Contraste , Ventrículos Cardíacos , Imagen por Resonancia Cinemagnética/métodos , Incidencia , Volumen Sistólico , Función Ventricular Izquierda , Intervención Coronaria Percutánea/métodosRESUMEN
Introduction: A higher 30-day mortality has been observed in patients with first-presentation ST elevation myocardial infarction (STEMI) who have no standard modifiable cardiovascular risk factors (SMuRFs), i. e., diabetes, hypertension, hyperlipidemia, and current smoker. In this study, we evaluate the clinical outcomes and CMR imaging characteristics of patients with and without SMuRFs who presented with first-presentation STEMI. Methods: Patients from the Third DANish Study of Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction (DANAMI-3) with first-presentation STEMI were classified into those with no SMuRFs vs. those with at least one SMuRF. Results: We identified 2,046 patients; 283 (14%) SMuRFless and 1,763 (86%) had >0 SMuRF. SMuRFless patients were older (66 vs. 61 years, p < 0.001) with more males (84 vs. 74%, p < 0.001), more likely to have left anterior descending artery (LAD) as the culprit artery (50 vs. 42%, p = 0.009), and poor pre-PCI (percutaneous coronary intervention) TIMI (thrombolysis in myocardial infarction) flow ≤1 (78 vs. 64%; p < 0.001). There was no difference in all-cause mortality, non-fatal reinfarction, or hospitalization for heart failure at 30 days or at long-term follow-up. CMR imaging was performed on 726 patients. SMuRFless patients had larger acute infarct size (17 vs. 13%, p = 0.04) and a smaller myocardial salvage index (42 vs. 50%, p = 0.02). These differences were attenuated when the higher LAD predominance and/or TIMI 0-1 flow were included in the model. Conclusion: Despite no difference in 30-day mortality, SMuRFless patients had a larger infarct size and a smaller myocardial salvage index following first-presentation STEMI. This association was mediated by a larger proportion of LAD culprits and poor TIMI flow pre-PCI. Clinical trial registration: clinicaltrials.gov, unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER) and NCT01960933 (DANAMI 3-PRIMULTI).
RESUMEN
BACKGROUND: In patients with ST-segment-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention, reperfusion injury accounts for a significant fraction of the final infarct size, which is directly related to patient prognosis. In animal studies, brief periods of ischemia in noninfarct-related (nonculprit) coronary arteries protect the culprit myocardium via remote ischemic preconditioning. Positive fractional flow reserve (FFR) documents functional significant coronary nonculprit stenosis, which may offer remote ischemic preconditioning of the culprit myocardium. The aim of the study was to investigate the association between functional significant, multivessel disease (MVD) and reduced culprit final infarct size or increased myocardial salvage (myocardial salvage index [MSI]) in a large contemporary cohort of STEMI patients. METHODS: Cardiac magnetic resonance was performed in 610 patients with STEMI at day 1 and 3 months after primary percutaneous coronary intervention. Patients were stratified into 3 groups according to FFR measurements in nonculprit stenosis (if any): angiographic single vessel disease (SVD), FFR nonsignificant MVD (functional SVD), or FFR-significant, functional MVD. RESULTS: A total of 431 (71%) patients had SVD, 35 (6%) had functional SVD, and 144 (23%) had functional MVD. There was no difference in final infarct size (mean infarct size [%left ventricular mass] SVD, 9±3%; functional SVD, 9±3%; and functional MVD, 9±3% [P=0.82]) or in MSI between groups (mean MSI [%left] SVD, 66±23%; functional SVD, 68±19%; and functional MVD, 69±19% [P=0.62]). In multivariable analyses, functional MVD was not associated with larger MSI (P=0.56) or smaller infarct size (P=0.55). CONCLUSIONS: Functional MVD in nonculprit myocardium was not associated with reduced culprit final infarct size or increased MSI following STEMI. This is important knowledge for future studies examining a cardioprotective treatment in patients with STEMI, as a possible confounding effect of FFR-significant, functional MVD can be discarded. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER) and NCT01960933 (DANAMI 3-PRIMULTI).
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Estenosis Coronaria/complicaciones , Vasos Coronarios/diagnóstico por imagen , Reserva del Flujo Fraccional Miocárdico/fisiología , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST/etiología , Volumen Sistólico/fisiología , Función Ventricular Izquierda/fisiología , Angiografía Coronaria , Estenosis Coronaria/diagnóstico , Estenosis Coronaria/fisiopatología , Vasos Coronarios/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Infarto del Miocardio con Elevación del ST/fisiopatología , Infarto del Miocardio con Elevación del ST/cirugía , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVES: This study investigated the incidence and long-term prognostic importance of multiple myocardial scars in cardiac magnetic resonance (CMR) in a large contemporary cohort of patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Patients presenting with STEMI may have multiple infarctions/scars caused by multiple culprit lesions, previous myocardial infarction (MI) or procedure-related MI due to nonculprit interventions. However, the incidence, long-term prognosis, and distribution of causes of multiple myocardial scars remain unknown. METHODS: CMR was performed in 704 patients with STEMI 1 day after primary percutaneous coronary intervention (PCI) and again 3 months later. Myocardial scars were assessed by late gadolinium enhancement (LGE). T2-weighted technique was used to differentiate acute from chronic infarctions. The presence of multiple scars was defined as scars located in different coronary territories. The combined endpoints of all-cause mortality and hospitalization for heart failure were assessed at 39 months (interquartile range [IQR]: 31 to 48 months). RESULTS: At 3 months, 59 patients (8.4%) had multiple scars. Of these, multiple culprits in STEMI were detected in 7 patients (1%), and development of a second nonculprit scar at follow-up occurred in 10 patients (1.4%). The most frequent cause of multiple scars was a chronic scar in the nonculprit myocardium. The presence of multiple scars was independently associated with an increased risk of all-cause mortality and hospitalization for heart failure (hazard ratio: 2.7; 95% confidence interval: 1.1 to 6.8; p = 0.037). CONCLUSIONS: Multiple scars were present in 8.4% of patients with STEMI and were independently associated with an increased risk of long-term morbidity and mortality. The presence of multiple myocardial scars on CMR may serve as a useful tool in risk stratification of patients following STEMI. (DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction [DANAMI-3]; NCT01435408) (Primary PCI in Patients With ST-elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization [PRIMULTI]; NCT01960933).
Asunto(s)
Cicatriz/diagnóstico por imagen , Imagen por Resonancia Magnética , Miocardio/patología , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Anciano , Cicatriz/mortalidad , Cicatriz/patología , Medios de Contraste/administración & dosificación , Dinamarca/epidemiología , Femenino , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Hospitalización , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/patología , Infarto del Miocardio con Elevación del ST/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: The aim of this study was to evaluate the effect of fractional flow reserve (FFR)-guided revascularization compared with culprit-only percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) on infarct size, left ventricular (LV), function, LV remodeling, and the presence of nonculprit infarctions. BACKGROUND: Patients with STEMI with multivessel disease might have improved clinical outcomes after complete revascularization compared with PCI of the infarct-related artery only, but the impact on infarct size, LV function, and remodeling as well as the risk for periprocedural infarction are unknown. METHODS: In this substudy of the DANAMI-3 (Third Danish Trial in Acute Myocardial Infarction)-PRIMULTI (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization) randomized trial, patients with STEMI with multivessel disease were randomized to receive either complete FFR-guided revascularization or PCI of the culprit vessel only. The patients underwent cardiac magnetic resonance imaging during index admission and at 3-month follow-up. RESULTS: A total of 280 patients (136 patients with infarct-related and 144 with complete FFR-guided revascularization) were included. There were no differences in final infarct size (median 12% [interquartile range: 5% to 19%] vs. 11% [interquartile range: 4% to 18%]; p = 0.62), myocardial salvage index (median 0.71 [interquartile range: 0.54 to 0.89] vs. 0.66 [interquartile range: 0.55 to 0.87]; p = 0.49), LV ejection fraction (mean 58 ± 9% vs. 59 ± 9%; p = 0.39), and LV end-systolic volume remodeling (mean 7 ± 22 ml vs. 7 ± 19 ml; p = 0.63). New nonculprit infarction occurring after the nonculprit intervention was numerically more frequent among patients treated with complete revascularization (6 [4.5%] vs. 1 [0.8%]; p = 0.12). CONCLUSIONS: Complete FFR-guided revascularization in patients with STEMI and multivessel disease did not affect final infarct size, LV function, or remodeling compared with culprit-only PCI.