Revascularization In ST-elevation Myocardial Infarction Research Articles

COMPARATIVE ANALYSIS OF STAGED VERSUS INDEX PROCEDURE COMPLETE REVASCULARIZATION IN ST-ELEVATION MYOCARDIAL INFARCTION

ST-elevation myocardial infarction (STEMI) is a critical condition that necessitates quick and efficient revascularization techniques. Recently, there has been a discussion on the best method for revascularization staged versus index procedure complete revascularization. The study compares the clinical outcomes of staged versus index procedure complete revascularization in ST-elevation myocardial infarction. This study is a prospective comparative analysis conducted at Ayub Teaching Hospital, Abbottabad. The patients were divided into two groups, with 40 participants in each group. Demographic data that included Smoking history, Diabetes mellitus, Dyslipidemia, Previous MI, and (LVEF) was recorded. Intraoperative and postoperative outcomes at 72 hours and six months were recorded. The quality of life was also assessed using SF-36 16. Data was entered and analyzed using SPSS (Statistical Package for the Social Sciences) version 24. P-values of ≤0.05 will be considered statistically significant. These findings suggest that in Group A, the frequency of "No reflow" (1 case) and "Abrupt closure" (0 instances) p=0.02) compared to Group B, where "No reflow" was observed in 2 cases and "Abrupt closure" in 1 case, (and (p=0.01), the investigation into post-operative outcomes, revealed no statistically significant differences between the two groups. P values ranged from 0.31 to 0.45, indicating comparable outcomes. After six months post-surgery, Group A demonstrated significantly better outcomes across various health-related domains than Group B, as indicated by the SF-36 questionnaire. In conclusion, index complete vascularization holds a distinct advantage over staged procedures. The observed differences across various health indicators highlight the potential clinical significance of prioritizing complete revascularization during the initial intervention.

Does MULTISTARS shed light on the timing of complete revascularization in ST-elevation myocardial infarction?

Does MULTISTARS shed light on the timing of complete revascularization in ST-elevation myocardial infarction?

Predicted clinical and economic burden associated with reduction in access to acute coronary interventional care during the COVID-19 lockdown in two European countries.

As a consequence of untimely or missed revascularization of ST-elevation myocardial infarction (STEMI) patients during the COVID-19 pandemic, many patients died at home or survived with serious sequelae, resulting in potential long-term worse prognosis and related health-economic implications.This analysis sought to predict long-term health outcomes [survival and quality-adjusted life-years (QALYs)] and cost of reduced treatment of STEMIs occurring during the first COVID-19 lockdown. Using a Markov decision-analytic model, we incorporated probability of hospitalization, timeliness of PCI, and projected long-term survival and cost (including societal costs) of mortality and morbidity, for STEMI occurring during the first UK and Spanish lockdowns, comparing them with expected pre-lockdown outcomes for an equivalent patient group.STEMI patients during the first UK lockdown were predicted to lose an average of 1.55 life-years and 1.17 QALYs compared with patients presenting with a STEMI pre-pandemic. Based on an annual STEMI incidence of 49 332 cases, the total additional lifetime costs calculated at the population level were £36.6 million (€41.3 million), mainly driven by costs of work absenteeism. Similarly in Spain, STEMI patients during the lockdown were expected to survive 2.03 years less than pre-pandemic patients, with a corresponding reduction in projected QALYs (-1.63). At the population level, reduced PCI access would lead to additional costs of €88.6 million. The effect of a 1-month lockdown on STEMI treatment led to a reduction in survival and QALYs compared to the pre-pandemic era. Moreover, in working-age patients, untimely revascularization led to adverse prognosis, affecting societal productivity and therefore considerably increasing societal costs.

Deferment of revascularization in ST-elevation myocardial infarction with coexisting aortic intramural hematoma.

Deferment of revascularization in ST-elevation myocardial infarction with coexisting aortic intramural hematoma.

Leveraging Existing STEMI Networks to Regionalize Cardiogenic Shock Systems of Care: Efforts to Expand the Scope Could Improve Shock Outcomes

Brief Summary Cardiogenic shock (CS) is a high-acuity and time-sensitive condition associated with significant morbidity and mortality that may be best served with centralized care by an experienced multi-disciplinary team. We propose that existing Canadian "hub-and-spoke" systems for timely revascularization in ST-elevation myocardial infarction can be leveraged to expand, and ultimately improve timely referral, transfer, and survival of CS patients.

Role of N-terminal pro-B-type natriuretic peptide and troponin T in predicting right ventricular recovery in myocardial infarction.

The determinants of right ventricular (RV) recovery after successful revascularization in ST-elevation myocardial infarction (STEMI) patients are not clear. Besides, the relationship between Troponin T (TnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and improvement in RV function is also unknown. This study hypothesizes that a lower TnT and NT-proBNP level would be associated with RV recovery. One hundred forty-eight STEMI patients were included in our study. Echocardiography were performed before and 12-18weeks after discharge. Patients were divided into three groups according to the changes in tricuspid annular plane systolic excursion (TAPSE) as 53 patients with≥10% change, 41 patients with 1-9% change, and 54 patients≤0% change. RV recovery was accepted as≥10% TAPSE improvement and the predictors of RV recovery were investigated. RV recovery was detected in 35.8% of the patients. Low baseline left ventricular ejection fraction (OR: 0.91 [0.84-0.98], p=0.023), NT-proBNP (OR: 0.93 [0.89-0.98], p=0.014), TnT (OR: 0.84 [0.68-0.93], p=0.038), inferior myocardial infarction (OR: 2.66 [1.10-6.40], p=0.028), wall motion score index ratio (OR: 0.93 [0.88-0.97], p=0.002) and post-percutaneous coronary intervention TIMI flow 3 (OR: 5.84 [1.41-24.22], p=0.015) were determined as independent predictors of RV recovery. Being in the high TnT group 4.2times, and being in the high NT-proBNP group 5.3 times could predict the failure to achieve RV recovery. Furthermore, when high TnT level was combined with high NT-proBNP level, the odds ratio of failure to achieve RV recovery was the highest (OR: 8.03 [2.59-24.89], p<0.001). Lower TnT and lower NT-proBNP level was associated with better improvement in RV function in STEMI patients.

TCT-225 Fractional Flow Reserve– or Angiography-Guided Revascularization for ST-Elevation Myocardial Infarction With Multivessel Disease: A Systematic Review and Network Meta-Analysis of Randomized Trials

TCT-225 Fractional Flow Reserve– or Angiography-Guided Revascularization for ST-Elevation Myocardial Infarction With Multivessel Disease: A Systematic Review and Network Meta-Analysis of Randomized Trials

Growth Differentiation Factor 15 is Related with Left Ventricular Recovery in Patients with ST-Elevation Myocardial Infarction after Successful Reperfusion by Primary Percutaneous Intervention.

The determinants of left ventricular (LV) recovery after successful revascularization in ST-elevation myocardial infarction (STEMI) patients are not clear. In addition, the relationship between growth differentiation factor15 (GDF-15) and left ventricular ejection fraction (LVEF) improvement is also unknown. This study hypothesizes that a low GDF-15 level would be associated with LVEF recovery. One hundred and sixty-one STEMI patients were included in this study. Echocardiographic examinations were performed before and 12-18 weeks after discharge. The patients were divided into three groups according to the changes in LVEF as 62 patients with ≥ 10% change, 47 patients with 1-9% change, and 52 patients ≤ 0% change. LV recovery was defined as ≥ 10% LVEF improvement and the predictors of LV recovery were investigated. Moreover, two groups were created according to GDF-15 values, and the follow-up/baseline echocardiographic parameters were compared between these groups. LV recovery was detected in 38.5% of the patients. Low baseline LVEF [odds ratio (OR): 0.85, 95% confidence interval (CI) 0.82-0.94, p = 0.001], low GDF-15 (OR: 0.79, 95% CI 0.68-0.93, p = 0.004), previous angina (OR: 2.34, 95% CI 1.10-4.96, p = 0.027), and symptom-to-balloon time (OR: 0.97, 95% CI 0.95-1.00, p = 0.043) were independent predictors of LV recovery. The ratios of follow-up/baseline LV end-diastolic volume index, LV end-systolic volume index and wall motion score index were lower in the low GDF-15 group (0.96 vs. 1.04, p < 0.001; 0.96 vs. 1.10, p < 0.001; 0.89 vs. 0.96, p < 0.001). Moreover, being in the low GDF-15 group was associated with LV recovery (OR: 2.93, 95% CI 1.43-6.02, p = 0.001). Lower GDF-15 level was associated with better LV improvement and less adverse remodeling in STEMI patients.

Timing of Nonculprit Percutaneous Coronary Intervention after ST-Elevation Myocardial Infarction

Introduction: Complete revascularization of ST-elevation myocardial infarction (STEMI) patients with multivessel disease (MVD) has recently shown to reduce risk of adverse cardiovascular events, including cardiovascular death. Optimal timing of revascularization of nonculprit lesions remains controversial. We aimed to measure cardiac outcomes related to duration between primary percutaneous coronary intervention (pPCI) of the culprit lesion and staged PCI (sPCI) of nonculprit lesions. Methods: From a prospectively collected consecutive registry of 3,002 patients treated for STEMI by pPCI, 1,555 patients with MVD requiring sPCI were identified. Patients were placed into quartiles of duration to sPCI: 0–7 days (Q1), 7–22 days (Q2), 22–42 days (Q3), >42 days (Q4), excluding those who had complete revascularization at the index event. Major adverse cardiac events (MACEs) included all-cause mortality, myocardial infarction, target vessel revascularization, and coronary artery bypass surgery. Cox regression and propensity score matching were performed correcting for confounding factors. Results: The average age at presentation was 65.7 ± 11.5 years. 333 were female (21.4%). Mean time between pPCI and sPCI was 28.3 days (±24.8). Rates of MACE were Q1 - 16.5%, Q2 - 21.2%, Q3 - 25.8%, and Q4 - 30.1% (log-rank <0.001). Following regression analysis, sPCI remained an independent risk factor for MACE (hazard ratio [HR] = 1.226 [95% confidence interval {CI}: 1.129–1.331, p < 0.001]). There was no association between the time interval up to sPCI with all-cause death (HR = 1.022 [95% CI: 0.925–1.129, p = 0.671]). Conclusions: Patients with MVD are at increased risk of experiencing MACE after revascularization of nonculprit vessels with increasing time delay between pPCI and sPCI.

Complete revascularization in STEMI with multivessel disease: how late is too late?

Abstract Funding Acknowledgements Type of funding sources: None. Background Recent research has shown that in patients (pts) with ST-elevation myocardial infarction (STEMI) and multivessel coronary disease, revascularization of non-culprit lesions soon after primary percutaneous coronary intervention (PCI) reduces the risk of death and myocardial infarction (MI) compared with culprit-lesion-only PCI. However, in real-world practice, centres often cannot perform PCI of non-culprit lesions as early after hospital discharge as reported in these studies. Purpose To analyse current treatment of STEMI with multivessel disease in a district hospital and determine if there is still benefit in doing complete revascularization (CR) even when non-culprit lesion PCI is done late after hospital discharge. Methods We conducted a retrospective pilot study including all consecutive pts with STEMI submitted to primary PCI in a district hospital in 2018 who presented angiographically significant multivessel disease amenable to PCI. We compared outcomes between pts who underwent CR after hospital discharge (study group), those who did it during hospitalization and the group who only underwent culprit-lesion PCI. Exclusion criteria included history of coronary bypass graft, cardiogenic shock at admission, a chronic total occlusion as single non-culprit lesion and death before treatment strategy was defined. Results Of the 302 pts treated for STEMI in 2018, 125 had multivessel disease. Of these, 27 met exclusion criteria, resulting in a sample of 98 pts with a mean age of 66 years. Median time from symptom onset to PCI was 5 hours, with 8% of pts presenting in Killip class II-III. Most pts (61%) underwent CR during index hospital stay. 15% underwent PCI of non-culprit lesions after hospital discharge, with a median time from primary to non-culprit PCI of 86 days. Finally, 18% underwent no further revascularization. An additional 5 pts had non-culprit lesions treated surgically after a median of 364 days. At a median follow-up of 2.4 years, death had occurred in none of the pts of the study group, which did not significantly differ from the 7 pts (12%) in the group revascularized at index hospitalization (log-rank test: p = 0.185) but was significantly inferior to the 5 (29%) in the culprit-only PCI group (p = 0.037). There was no significant difference in a composite outcome of death, MI and stroke. The secondary outcome of ischaemia-driven revascularization occurred more often in the study group compared with those revascularized during hospitalization (HR 6.68; 95% CI 1.09-41.01; p = 0.040). Conclusions This study suggests that complete revascularization in STEMI with multivessel disease even late after hospital discharge is still superior to culprit-lesion only PCI in reducing risk of death. On the other hand, this late revascularization seems to be associated with higher rates of ischaemia-induced revascularization. Further research with a larger sample will be required to confirm the results of this pilot study.

Abstract 17438: Sex Differences and Temporal Trends in Revascularization and Outcomes of ST-Elevation Myocardial Infarction in Older Adults in the United States

Background: Prior studies have suggested that women with ST-elevation myocardial infarction (STEMI) have higher in-hospital mortality risk than younger men with STEMI. However, there is a significant STEMI risk in older patients. We analyzed temporal trends and sex differences in revascularization and other in-hospital outcomes in older STEMI patients. Methods: National Inpatient Sample databases from 2005 to 2014 were utilized to identify all STEMI patients with age greater than 60 years old. We studied the temporal trends and sex differences in revascularization therapies and in-hospital mortality. Results: There were N=192,204 older adults diagnosed with STEMI. Older women with STEMI were less likely to undergo coronary angiography (adjusted OR: 0.90; 95% CI: 0.88 to 0.93) and receive reperfusion (percutaneous coronary intervention (PCI) adjusted OR: 0.90; 95% CI: 0.87 to 0.92) compared to older men. Also, the adjusted odds ratio comparing the likelihood of receiving PCI between women and men decreased by an annual average of 0.9% (P=0.028). Older men were more likely to receive PCI on Hospital Day 0 compared to older women. There was a decreasing trend in both sexes for use of coronary artery bypass graft (CABG), though older men consistently underwent CABG more often than older women (Figure). Older women had higher in-hospital mortality than men (adjusted OR: 1.12; 95% CI: 1.08 to 1.17). However, the differences decreased with increasing patient age. There was no significant change in adjusted in-hospital mortality in both genders (all P&gt;0.05). Conclusions: Older women were less likely to receive revascularization for STEMI than men, and this gap increased over the study period. Older women had higher in-hospital mortality compared with older men, but there was no significant temporal change for both genders. Further research is needed to identify the reasons why older women receive less revascularization.

Updated Review on Revascularization in ST-elevation Myocardial Infarction (STEMI)

Effective and in time reperfusion of the infarct-related coronary artery is essential to optimal treatment for ST-elevation myocardial infarction (STEMI). Now it is established the benefit of primary percutaneous intervention (PPCI) in STEMI over fibrinolysis. While intervention of the non-infarct related artery still a large area of debate with no definite consensus. Here in this review we will highlight the different reperfusion strategies and different ways to reach optimal reperfusion and debate about non-IRA in different situations.

The impact of incomplete revascularization on early and late outcomes in ST-elevation myocardial infarction

In ST-elevation myocardial infarction (STEMI) in patients with multivessel disease, there is a lack of consensus regarding the importance of complete revascularization and the timing of treatment of nonculprit stenoses. Our objective was to investigate the impact of incomplete revascularization in STEMI patients using the residual Synergy Between PCI with TAXUS and Cardiac Surgery score (rSS) to define completeness of revascularization. This study examined associations between incomplete revascularization, determined by the rSS, and the combined outcome of cardiac death and myocardial infarction (MI). Patients were divided into groups: rSS = 0 (complete revascularization), rSS = 1-8 (incomplete revascularization with a low burden of residual disease), or rSS >8 (incomplete revascularization with a high burden of residual disease). The rSS score was calculated in 589 consecutive patients; 25% had an rSS of 0, 42% rSS 1-8, and 33% rSS >8. At median follow-up of 3.5 years, cardiac death and MI occurred in 5% of rSS = 0 patients, 15% rSS = 1-8, and 26% with rSS >8 (P < .001). The rSS was powerful independent predictor of cardiac death and MI (hazard ratio 5.05, CI 2.89-12.00, rSS >8 vs rSS 0, P < .001 and hazard ratio 2.96, CI 1.31-6.69, rSS = 1-8 vs rSS = 0, P = .009), respectively, and an independent predictor of mortality, MI, unplanned revascularization, and major adverse cardiovascular events. In patients with STEMI, the rSS independently predicts cardiac death and MI. Patients with an rSS >8 had substantially higher rates of cardiac death or MI. The rSS can be used to define incomplete revascularization in STEMI and predict adverse outcomes.

Clinical depression and anxiety among ST-elevation myocardial infarction hospitalizations: Results from Nationwide Inpatient Sample 2004–2013

Depression and anxiety are common among patients who have a major cardiovascular event. However, despite their frequency, there is a lack of evidence regarding the relationship between depression and/or anxiety and receiving revascularization in ST-elevation myocardial infarction (STEMI) hospitalizations. Using data from the Nationwide Inpatient Sample (NIS) from the years 2004 to 2013, we assessed whether a clinical co-diagnosis of depression and/or anxiety decreases the likelihood of revascularization among STEMI hospitalizations. Our central finding is that, paradoxically, the odds of in-hospital mortality were lower among STEMI hospitalizations with a clinical co-diagnosis of depression and/or anxiety as compared to those without. We further discovered that clinical diagnoses of depression and/or anxiety were less prevalent among revascularized as compared to non-revascularized STEMI hospitalizations. However, the percentage of clinical diagnoses of depression and/or anxiety among STEMI hospitalizations increased at a similar rate over a 10-year period irrespective of revascularization status. In conclusion, these results are suggestive of the potentially underdiagnosed mental health issues surrounding major cardiovascular events, and indeed, chronic disease as a whole. To our knowledge, this is the first study to document and examine the “depression paradox” among a population of cardiac patients.

Complete versus culprit only revascularization in ST-elevation myocardial infarction-a perspective on recent trials and recommendations.

The presence of multivessel coronary artery disease (CAD) is strongly associated with higher 30-day mortality, reduced myocardial reperfusion success, reinfarction, and occurrence of major adverse cardiac events (MACE) at 1 year compared with single-vessel CAD. Despite higher morbidity and mortality in patients with ST-elevation myocardial infarction (STEMI) and coexistent multivessel CAD, major guidelines recommended against percutaneous coronary intervention (PCI) on non-culprit lesions at the time of primary PCI in patients with STEMI who are hemodynamically stable. The presence of multivessel CAD often poses a therapeutic dilemma for interventional cardiologists. A few larger scale randomized controlled trials (RCTs) and meta-analyses have been conducted. The conclusions regarding multivessel PCI generally trend towards lower risk of MACE, repeat revascularization, with similar risks of recurrent myocardial infarction (MI) and mortality. However, none of the RCTs were adequately powered for hard outcomes of death and MI.

Comparison of Outcomes of Staged Complete Revascularization Versus Culprit Lesion–Only Revascularization for ST-Elevation Myocardial Infarction and Multivessel Coronary Artery Disease

The management of noninfarct-related arteries in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary disease (MVD) is still debated. We evaluated the prognostic impact of staged complete revascularization with percutaneous coronary intervention (PCI) in STEMI patients with MVD admitted to our hospital from 2005 to 2013. Patients undergoing staged complete revascularization (n= 300) were compared with 1:1 propensity score-matched patients with culprit lesion-only treatment (n= 300). We considered a composite primary end point of all-cause death, myocardial infarction, and urgent PCI. Secondary end points included components of the primary, cardiovascular death, any PCI excluding staged PCI. We also performed an analysis including only patients surviving at least 5days. The median follow-up was 553days. The primary end point occurred in 10.3% of patients in the staged complete revascularization group and in 16.3% of patients in the culprit lesion-only group (hazard ratio 0.61, 95% CI 0.38 to 0.95, p= 0.031). Although this difference was no longer significant when considering only the survivors at day 5, all-cause and cardiovascular mortalities were still reduced in the staged complete revascularization group. Complete revascularization was associated with a better outcome (hazard ratio 0.35, 95% CI 0.17 to 0.63, p= 0.005) if performed within 30days of STEMI. In conclusion, compared with culprit lesion-only revascularization, in STEMI patients with MVD undergoing primary PCI, an approach of staged complete revascularization was associated with a better outcome.

Complete versus target vessel revascularization in ST-elevation myocardial infarction-analysis of results from published meta-analysis of randomized controlled trials.

We thank Weng et al . for their interest in our recent paper where we performed an updated meta-analysis of the benefits of non-culprit revascularization during an ST elevation myocardial infarction (STEMI) (1). The authors used trial sequence analysis (TSA) to further explore the results of our meta-analysis. The results of their TSA (2) confirmed the lower incidence of major adverse cardiac events and repeat revascularization among patients undergoing non-culprit lesion intervention. They also hypothesized that our finding of similar all-cause mortality may be a type II error (false negative) and the demonstration of lower myocardial infarction may be a type 1 error (false positive).

Dysglycemia in patients with ST-elevation myocardial infarction

Introduction Dyglycemia on admission is associated with increased mortality rates in patients with ST-elevation myocardial infarction (STEMI). Aim Investigate the relationship between dysglycemia and angiographic and clinical outcome after primary or rescue angioplasty for STEMI. Methods We prospectively included 188 patients who underwent revascularization for STEMI. We compared intrahospital outcomes between the groups of patients with HG (HG + ) and without HG (HG-). Plasma glucose was measured at hospital admission. HG was defined as plasma glucose > 11 mmol/L. Results Among the overall population, 60 (31.9 %) patients had HG. The mean age was 60.77 ± 11.79 years. They were more frequently men (84.4 %) with a more frequent history of diabetes and hypertension. A total of 19 cases (31.7 % of the study group) of newly diagnosed diabetes mellitus were registered. In subjects with higher admission glucose the maximal levels of troponin I were higher, as well as maximal values of creatine phosphokinase. Coronary status was more severe in HG+ (52.6 % vs. 47.4 %, p = 0.003). Procedural success was lower in the HG+ group (31.4 % vs. 68.6 %) with higher rates of per-procedural complications (51.6 % vs. 48.4 %, p = 0.019). Intrahospital outcomes were worse in the HG+ group as attested by a higher mortality (3.19 % vs. 4.25 %, p = 0.043). Those outcomes were similar in the HG+ group regardless to the diabetic status. Conclusion Hyperglycemia on admission is associated with greater myocardial injury and an increased risk of major adverse cardiovascular events at long-term follow-up.

Complete versus culprit-only revascularization in ST-elevation myocardial infarction and multivessel disease.

In 30-60% of patients presenting with ST-segment elevation myocardial infarction (STEMI), significant stenoses are present in one or more non-infarct-related arteries (IRA). This correlates with an increased risk of major adverse cardiac events (MACE). Current guidelines, do not recommend revascularization of non-culprit lesions unless complicated by cardiogenic shock or persistent ischemia after primary percutaneous coronary intervention (PCI). Prior observational and small randomized controlled trials (RCTs) have demonstrated conflicting results regarding the optimal revascularization strategy in STEMI patients with multivessel disease. Recently, randomized studies (PRAMI, CvLPRIT, and DANAMI 3-PRIMULTI) provide encouraging data that suggest potential benefit with complete revascularization in STEMI patients with obstructive non-culprit lesions. Differently, in the PRAGUE-13 trial there were no differences in MACE between complete revascularization and culprit-only PCI. Several meta-analyses were recently published including randomized and non-randomized clinical trials, showing different results depending on the included trials. In conclusion, the current available evidence from the randomized clinical trials, with a total sample size of only 2000 patients, is not robust enough to firmly recommend complete revascularization in STEMI patients. This uncertainty lends support to the continuation of the COMPLETE trial. This ongoing trial is anticipated to enroll 3900 patients with STEMI from across the world, and will be powered for the hard outcomes of death and myocardial infarction. Until the results of the COMPLETE trial are reported, physicians need to individualize care regarding the opportunity and the timing of the non-IRA PCI.

Papillary Muscle Rupture Following Non‐ST‐Elevation Myocardial Infarction: A Case Report

Papillary muscle rupture is a serious mechanical complication of acute myocardial infarction typically seen within 5-7 days following transmural ST-elevation myocardial infarction. The incidence of papillary muscle rupture has markedly decreased in the modern era due to improved diagnosis and early coronary revascularization of ST-elevation myocardial infarction. As a result, papillary muscle rupture is increasingly seen following non-ST-elevation myocardial infarction where both diagnosis and revascularization can be delayed. In this report, we describe two cases of papillary muscle rupture following delayed presentation of non-ST-elevation myocardial infarction and delayed recognition of papillary muscle rupture.