Ten-year mortality after treating obstructive coronary atherosclerosis with contemporary stents in patients with or without concomitant peripheral arterial disease.

BACKGROUND AND AIMS: Previous studies in percutaneous coronary intervention (PCI) patients showed a higher 3-year adverse event risk, including all-cause mortality, in those with concomitant peripheral arterial disease (PADs). Ten-year data of mortality and causes of death are scarce. This analysis assessed PCI patients, treated with contemporary drug-eluting stents, the impact of concomitant PADs on very long-term mortality, and causes of death. METHODS: We assessed PCI all-comers from our center who participated in the TWENTE and DUTCH PEERS trials (clinicaltrials.gov:NCT01066650, NCT01331707), comparing patients with versus without PADs. Life status was checked in the Dutch Personal Records Database; causes of death were obtained from medical records. RESULTS: Of 2705 study patients, 668 (24.7%) died during follow-up: 88/212 (41.5%) patients with PADs and 580/2493 (23.1%) without PADs. In PADs patients, the 10-year rate of all-cause mortality was about twice as high as in patients without PADs (41.5% vs.23.1%, HR: 2.05, 95%-CI: 1.64-2.57, p<0.001). For both groups, the rates of patients dying from various causes of death were: cardiac (14.1% vs.6.8%), vascular (2.8% vs. 1.1%), non-cardiovascular (17.4% vs. 9.8%), and unclear causes (7.1% vs. 5.3%), without a statistically significant between-group difference. When multivariate analysis was adjusted for between-group differences in cardiovascular risk profile, PADs remained predictor of all-cause mortality (adjusted HR: 1.38, 95%-CI: 1.08-1.75, p=0.01). CONCLUSIONS: The 10-year all-cause mortality rate in PCI patients with concomitant PADs was almost twice as high as in those without PADs. Age and other traditional cardiovascular risk factors were higher in patients with PADs, but after correction for these confounders PADs still accounted for almost 40% increase in mortality.

Impact of the number of modifiable risk factors on clinical outcomes after percutaneous coronary intervention: An analysis from the e-Ultimaster registry.

Aims: A substantial proportion of the patients undergoing percutaneous coronary intervention (PCI) have none of the of standard modifiable cardiovascular risk factors (SMuRFs): hypertension, diabetes, hypercholesterolaemia and smoking. The aim of this analysis was to compare clinical outcomes after PCI according to the number of SMuRFs. Methods: Patients with an indication for a PCI were stratified based upon the number of SMuRFs: 0, 1, 2 or 3-4. The primary outcome was target lesion failure (TLF), a composite of cardiac death, target vessel-related myocardial infarction or clinically driven target lesion revascularization at 1-year. Inverse weighted propensity score (IWPS) adjustment was performed to adjust for differences in baseline characteristics. Results: The prevalence of SMuRFs was: 0 SMuRF 16.4 %; 1 SMuRF 27.8 %; 2 SMuRFs 34.7 % and 3-4 SMuRFs 21.1 %. Patients without SMuRFs were younger, more likely to be male and had less complex coronary artery disease. The incidence of TLF increased with the number of SMuRFs: 2.65 %, 2.75 %, 3.23 %, and 4.24 %, Ptrend < 0.001. The relative risk (RR) for a TLF was 60 % higher (95 % confidence interval 1.32-1.93, p < 0.01) for patients with 3-4 SMuRFs compared to patients without SMuRFs. The trend remained (Ptrend < 0.01) after IWPS with TLF rates of 2.88 %, 2.64 %, 2.88 % and 3.65 %. The RR for a TLF was 27 % higher (95 % CI 1.05-1.53, p < 0.01). Conclusion: The incidence of clinical events at 1-year increased with the number of SMuRFs. While patients without SMuRFs have a relatively favourable risk profile, more research is needed to optimize therapeutic management in the majority of patients.

Invasiveness of previous treatment for peripheral arterial disease and risk of adverse cardiac events after coronary stenting.

Patients with peripheral arterial disease (PADs), undergoing percutaneous coronary intervention (PCI), have higher adverse event risks. The effect of invasiveness of PADs treatment on PCI outcome is unknown. This study assessed the impact of the invasiveness of previous PADs treatment (invasive or non-invasive) on event risks after PCI with contemporary drug-eluting stents. This post-hoc analysis pooled 3-year patient-level data of PCI all-comer patients living in the eastern Netherlands, previously treated for PADs. PADs included symptomatic atherosclerotic lesion in the lower or upper extremities; carotid or vertebral arteries; mesenteric arteries or aorta. Invasive PADs treatment comprised endarterectomy, bypass surgery, percutaneous transluminal angioplasty, stenting or amputation; non-invasive treatment consisted of medication and participation in exercise programs. Primary endpoint was (coronary) target vessel failure: composite of cardiac mortality, target vessel-related myocardial infarction, or clinically indicated target vessel revascularization. Of 461 PCI patients with PADs, information on PADs treatment was available in 357 (77.4%) patients; 249 (69.7%) were treated invasively and 108 (30.3%) non-invasively. Baseline and PCI procedural characteristics showed no between-group difference. Invasiveness of PADs treatment was not associated with adverse event risks, including target vessel failure (20.5% vs. 16.0%; HR: 1.30, 95%-CI 0.75-2.26, p = 0.35), major adverse cardiac events (23.3% vs. 20.4%; HR: 1.16, 95%-CI 0.71-1.90, p = 0.55), and all-cause mortality (12.1% vs. 8.3%; HR: 1.48, 95%-CI 0.70-3.13, p = 0.30). In PADs patients participating in PCI trials, we found no significant relation between the invasiveness of previous PADs treatment and 3-year outcome after PCI. Consequently, high-risk PCI patients can be identified by consulting medical records, searching for PADs, irrespective of the invasiveness of PADs treatment.

Routine transthoracic echocardiography in ischaemic stroke or transient ischaemic attack of undetermined cause: a prospective multicentre study.

BACKGROUND: Guidelines recommend routine transthoracic echocardiography (TTE) after ischaemic stroke or transient ischaemic attack of undetermined cause; yet, only limited scientific evidence exists. Therefore, we aimed to determine in these patients the prevalence of TTE-detected major cardiac sources of embolism (CSE), which are abnormalities leading to therapeutic changes. METHODS: Six Dutch hospitals conducted a prospective observational study that enrolled patients with ischaemic stroke or transient ischaemic attack of undetermined cause. Patients underwent TTE after comprehensive diagnostic evaluation on stroke units, including blood chemistry, 12-lead electrocardiogram (ECG), ≥ 24 h continuous ECG monitoring, brain imaging and cervical artery imaging. Primary outcome measure was the proportion of patients with TTE-detected major CSE. RESULTS: From March 2018 to October 2020, 1084 patients, aged 66.6 ± 12.5 years, were enrolled; 456 (42.1%) patients were female and 869 (80.2%) had ischaemic stroke. TTE detected major CSE in only 11 (1.0%) patients. Ten (90.9%) of these patients also had major ECG abnormalities (previous infarction, major repolarisation abnormalities, or previously unknown left bundle branch block) that would have warranted TTE assessment regardless of stroke evaluation. Such ECG abnormalities were present in 11.1% of the total study population. A single patient (0.1%) showed a major CSE despite having no ECG abnormality. CONCLUSIONS: This multicentre cross-sectional study in patients who-after workup on contemporary stroke units-were diagnosed with ischaemic stroke or transient ischaemic attack of undetermined cause found TTE-detected major CSE in only 1% of all patients. Most of these patients also had major ECG abnormalities. These findings question the value of routine TTE assessment in this clinical setting.

Atrial fibrillation detected with outpatient cardiac rhythm monitoring in patients with ischemic stroke or TIA of undetermined cause.

OBJECTIVES: Guidelines advise cardiac rhythm monitoring for 3 up to 30 days for detecting atrial fibrillation (AF) in patients with ischemic stroke of undetermined cause. However, the optimal monitoring duration is unknown. We aimed to determine the AF detection rate during 7-day outpatient cardiac rhythm monitoring in this patient group. METHODS: Participants from a large tertiary hospital in a prospective observational study (ATTEST) underwent outpatient cardiac rhythm monitoring after a negative standard diagnostic evaluation (i.e., 12-lead electrocardiogram and in-hospital telemetry). Primary outcome was the rate of newly detected AF. RESULTS: We examined 373 patients [age: 67.8±11.6 years; women: 166(44.5%); stroke: 278(74.5%)]. Median monitoring duration was 7 days (Inter Quartile Range (IQR) 7-7), performed after median of 36 days (IQR 27-47). AF was newly detected in 17(4.6%) patients, 5.4% of patients with ischemic stroke and 2.1% of patients with TIA. 53% of AF was detected on day-1, after day-3 73% of new AF was found. First AF episodes were detected up to day-7. Diabetes and increasing age were independent predictors of new AF. CONCLUSION: After ischemic stroke or TIA of undetermined cause, 7-day outpatient cardiac rhythm monitoring detected new AF in 4.6%. Patients with AF had significantly more cardiovascular risk factors. Although about 50% of first AF episodes occurred during the first day of monitoring, new AF was detected up to day-7, implying that the recommended minimum of 3 days cardiac rhythm monitoring after ischemic stroke of undetermined cause is insufficient. Subsequent long-term rhythm monitoring should be considered in selected patients.

Outcome of percutaneous coronary intervention using ultrathin-strut biodegradable polymer sirolimus-eluting versus thin-strut durable polymer zotarolimus-eluting stents in patients with comorbid peripheral arterial disease: a post-hoc analysis from two randomized trials.

Background: In patients with peripheral arterial disease (PADs), who underwent percutaneous coronary intervention (PCI), little is known about the potential impact of using different new-generation drug-eluting stents (DES) on outcome. In PCI all-comers, the results of most between-stent comparisons-stratified by strut thickness-suggested some advantage of coronary stents with ultrathin-struts. The current post-hoc analysis aimed to assess outcomes of PCI with ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) vs. thin-strut durable polymer zotarolimus-eluting stents (DP-ZES) in patients with PADs. Methods: We pooled 3-year patient-level data from two large-scale randomized all-comer trials to compare Orsiro ultrathin-strut BP-SES vs. Resolute-type thin-strut DP-ZES in trial participants with concomitant PADs. BIO-RESORT (December 2012 to August 2015) and BIONYX (October 2015 to December 2016) included all-comer patients who were aged 18 years or older, capable of providing informed consent, and required a PCI. The trials had web-based randomization, with block sizes of 4 and 8, performed in a 1:1:1 or 1:1 fashion. Assessors, research staff, and patients were blinded to the type of stent used. We assessed the composite main clinical endpoint target vessel failure [TVF: cardiac death, target vessel related myocardial infarction (MI), or clinically indicated target vessel revascularization (TVR)], its components, and stent thrombosis. Results: Of 4,830 trial participants, 360 had PADs: 177 (49.2%) were treated with BP-SES and 183 (50.8%) with DP-ZES. Baseline characteristics were similar. For BP-SES, the 3-year TVF rate was 11.0% and for DP-ZES 17.9% [hazard ratio (HR): 0.59, 95% CI: 0.33-1.04; P=0.07]. For BP-SES, the TVR rate was lower than for DP-ZES (4.1% vs. 11.0%; HR: 0.36, 95% CI: 0.15-0.86; P=0.016), but this did not translate into between-group differences in cardiac death or MI. In small vessels (<2.75 mm), the TVR rate was also lower in BP-SES (5.6% vs. 13.9%; HR: 0.32, 95% CI: 0.11-0.91; P=0.024). Definite-or-probable stent thrombosis rates were 1.2% and 2.3% (P=0.43). Conclusions: In PCI patients with PADs, the 3-year TVF incidence was numerically lower in the ultrathin-strut BP-SES vs. the thin-strut DP-ZES group. Furthermore, TVR risk was significantly lower in ultrathin-strut BP-SES, mainly driven by a lower TVR rate in small vessels. Trial Registration: BIO-RESORT trial: clinicaltrials.gov (NCT01674803); BIONYX trial: clinicaltrials.gov (NCT02508714).

Impact of premature coronary artery disease on adverse event risk following first percutaneous coronary intervention.

Objectives: We assessed differences in risk profile and 3-year outcome between patients undergoing percutaneous coronary intervention (PCI) for premature and non-premature coronary artery disease (CAD). Background: The prevalence of CAD increases with age, yet some individuals develop obstructive CAD at younger age. Methods: Among participants in four randomized all-comers PCI trials, without previous coronary revascularization or myocardial infarction (MI), we compared patients with premature (men <50 years; women <55 years) and non-premature CAD. Various clinical endpoints were assessed, including multivariate analyses. Results: Of 6,171 patients, 887 (14.4%) suffered from premature CAD. These patients had fewer risk factors than patients with non-premature CAD, but were more often smokers (60.7% vs. 26.4%) and overweight (76.2% vs. 69.8%). In addition, premature CAD patients presented more often with ST-segment elevation MI and underwent less often treatment of multiple vessels, and calcified or bifurcated lesions. Furthermore, premature CAD patients had a lower all-cause mortality risk (adj.HR: 0.23, 95%-CI: 0.10-0.52; p < 0.001), but target vessel revascularization (adj.HR: 1.63, 95%-CI: 1.18-2.26; p = 0.003) and definite stent thrombosis risks (adj.HR: 2.24, 95%-CI: 1.06-4.72; p = 0.034) were higher. MACE rates showed no statistically significant difference (6.6% vs. 9.4%; adj.HR: 0.86, 95%-CI: 0.65-1.16; p = 0.33). Conclusions: About one out of seven PCI patients was treated for premature CAD. These patients had less complex risk profiles than patients with non-premature CAD; yet, their risk of repeated revascularization and stent thrombosis was higher. As lifetime event risk of patients with premature CAD is known to be particularly high, further efforts should be made to improve modifiable risk factors such as smoking and overweight. TWENTE trials: (TWENTE I, clinicaltrials.gov: NCT01066650), DUTCH PEERS (TWENTE II, NCT01331707), BIO-RESORT (TWENTE III, NCT01674803), and BIONYX (TWENTE IV, NCT02508714).

First myocardial infarction in patients with premature coronary artery disease: insights into patient characteristics and outcome after treatment with contemporary stents.

AIMS: Patients with premature coronary artery disease (CAD) have a higher incidence of myocardial infarction (MI) than patients with non-premature CAD. The aim of the present study is to asess differences in clinical outcome after a first acute MI, percutaneously treated with new-generation drug-eluting stents between patients with premature and non-premature CAD. METHODS AND RESULTS: We pooled and analysed the characteristics and clinical outcome of all patients with a first MI (and no previous coronary revascularization) at time of enrolment, in four large-scale drug-eluting stent trials. Coronary artery disease was classified premature in men aged <50 and women <55 years. Myocardial infarction patients with premature and non-premature CAD were compared. The main endpoint was major adverse cardiac events (MACE): all-cause mortality, any MI, emergent coronary artery bypass surgery, or clinically indicated target lesion revascularization. Of 3323 patients with a first MI, 582 (17.5%) had premature CAD. These patients had lower risk profiles and underwent less complex interventional procedures than patients with non-premature CAD. At 30-day follow-up, the rates of MACE [hazard ratio (HR): 0.22, 95% confidence interval (CI): 0.07-0.71; P = 0.005), MI (HR: 0.22, 95% CI: 0.05-0.89; P = 0.020), and target vessel failure (HR: 0.30, 95% CI: 0.11-0.82; P = 0.012) were lower in patients with premature CAD. At 1 year, premature CAD was independently associated with lower rates of MACE (adjusted HR: 0.50, 95% CI: 0.26-0.96; P = 0.037) and all-cause mortality (adjusted HR: 0.24, 95% CI: 0.06-0.98; P = 0.046). At 2 years, premature CAD was independently associated with lower mortality (adjusted HR: 0.16, 95% CI: 0.05-0.50; P = 0.002). CONCLUSIONS: First MI patients with premature CAD, treated with contemporary stents, showed lower rates of MACE and all-cause mortality than patients with non-premature CAD, which is most likely related to differences in cardiovascular risk profile. TWENTE trials: TWENTE I, clinicaltrials.gov: NCT01066650), DUTCH PEERS (TWENTE II, NCT01331707), BIO-RESORT (TWENTE III, NCT01674803), and BIONYX (TWENTE IV, NCT02508714).

Impact of chronic kidney disease and diabetes on clinical outcomes in women undergoing PCI.

BACKGROUND: For women undergoing drug-eluting stent (DES) implantation, the individual and combined impact of chronic kidney disease (CKD) and diabetes mellitus (DM) on outcomes is uncertain. AIMS: We sought to assess the impact of CKD and DM on prognosis in women after DES implantation. METHODS: We pooled patient-level data on women from 26 randomised controlled trials comparing stent types. Women receiving DES were stratified into 4 groups based on CKD (defined as creatine clearance <60 mL/min) and DM status. The primary outcome at 3 years after percutaneous coronary intervention was the composite of all-cause death or myocardial infarction (MI); secondary outcomes included cardiac death, stent thrombosis and target lesion revascularisation. RESULTS: Among 4,269 women, 1,822 (42.7%) had no CKD/DM, 978 (22.9%) had CKD alone, 981 (23.0%) had DM alone, and 488 (11.4%) had both conditions. The risk of all-cause death or MI was not increased in women with CKD alone (adjusted hazard ratio [adj. HR] 1.19, 95% confidence interval [CI]: 0.88-1.61) nor DM alone (adj. HR 1.27, 95% CI: 0.94-1.70), but was significantly higher in women with both conditions (adj. HR 2.64, 95% CI: 1.95-3.56; interaction p-value <0.001). CKD and DM in combination were associated with an increased risk of all secondary outcomes, whereas alone, each condition was only associated with all-cause death and cardiac death. CONCLUSIONS: Among women receiving DES, the combined presence of CKD and DM was associated with a higher risk of the composite of death or MI and of any secondary outcome, whereas alone, each condition was associated with an increase in all-cause and cardiac death.

Predictors of target lesion failure after treatment of left main, bifurcation, or chronic total occlusion lesions with ultrathin-strut drug-eluting coronary stents in the ULTRA registry.

BACKGROUND: Data about the long-term performance of new-generation ultrathin-strut drug-eluting stents (DES) in challenging coronary lesions, such as left main (LM), bifurcation, and chronic total occlusion (CTO) lesions are scant. METHODS: The international multicenter retrospective observational ULTRA study included consecutive patients treated from September 2016 to August 2021 with ultrathin-strut (<70 µm) DES in challenging de novo lesions. Primary endpoint was target lesion failure (TLF): composite of cardiac death, target-lesion revascularization (TLR), target-vessel myocardial infarction (TVMI), or definite stent thrombosis (ST). Secondary endpoints included all-cause death, acute myocardial infarction (AMI), target vessel revascularization, and TLF components. TLF predictors were assessed with Cox multivariable analysis. RESULTS: Of 1801 patients (age: 66.6 ± 11.2 years; male: 1410 [78.3%]), 170 (9.4%) experienced TLF during follow-up of 3.1 ± 1.4 years. In patients with LM, CTO, and bifurcation lesions, TLF rates were 13.5%, 9.9%, and 8.9%, respectively. Overall, 160 (8.9%) patients died (74 [4.1%] from cardiac causes). AMI and TVMI rates were 6.0% and 3.2%, respectively. ST occurred in 11 (1.1%) patients while 77 (4.3%) underwent TLR. Multivariable analysis identified the following predictors of TLF: age, STEMI with cardiogenic shock, impaired left ventricular ejection fraction, diabetes, and renal dysfunction. Among the procedural variables, total stent length increased TLF risk (HR: 1.01, 95% CI: 1-1.02 per mm increase), while intracoronary imaging reduced the risk substantially (HR: 0.35, 95% CI: 0.12-0.82). CONCLUSIONS: Ultrathin-strut DES showed high efficacy and satisfactory safety, even in patients with challenging coronary lesions. Yet, despite using contemporary gold-standard DES, the association persisted between established patient- and procedure-related features of risk and impaired 3-year clinical outcome.

Age-Related Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry.

BACKGROUND: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. METHODS: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March-June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. RESULTS: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825-0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24-1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05-1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic.

Gender Difference in the Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry.

BACKGROUND: Several reports have demonstrated the impact of the COVID-19 pandemic on the management and outcome of patients with ST-segment elevation myocardial infarction (STEMI). The aim of the current analysis is to investigate the potential gender difference in the effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI patients within the ISACS-STEMI COVID-19 Registry. METHODS: This retrospective multicenter registry was performed in high-volume primary percutaneous coronary intervention (PPCI) centers on four continents and included STEMI patients undergoing PPCIs in March-June 2019 and 2020. Patients were divided according to gender. The main outcomes were the incidence and timing of the PPCI, (ischemia time ≥ 12 h and door-to-balloon ≥ 30 min) and in-hospital or 30-day mortality. RESULTS: We included 16683 STEMI patients undergoing PPCIs in 109 centers. In 2020 during the pandemic, there was a significant reduction in PPCIs compared to 2019 (IRR 0.843 (95% CI: 0.825-0.861, p < 0.0001). We did not find a significant gender difference in the effects of the COVID-19 pandemic on the numbers of STEMI patients, which were similarly reduced from 2019 to 2020 in both groups, or in the mortality rates. Compared to prepandemia, 30-day mortality was significantly higher during the pandemic period among female (12.1% vs. 8.7%; adjusted HR [95% CI] = 1.66 [1.31-2.11], p < 0.001) but not male patients (5.8% vs. 6.7%; adjusted HR [95% CI] = 1.14 [0.96-1.34], p = 0.12). CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures similarly observed in both genders. Furthermore, we observed significantly increased in-hospital and 30-day mortality rates during the pandemic only among females. Trial registration number: NCT 04412655.

Impact of multisite artery disease on clinical outcomes after percutaneous coronary intervention: an analysis from the e-Ultimaster registry.

BACKGROUND: Multisite artery disease is considered a 'malignant' type of atherosclerotic disease associated with an increased cardiovascular risk, but the impact of multisite artery disease on clinical outcomes after percutaneous coronary intervention (PCI) is unknown. METHODS: Patients enrolled in the large, prospective e-Ultimaster study were grouped into (1) those without known prior vascular disease, (2) those with known single-territory vascular disease, and (3) those with known two to three territories (i.e coronary, cerebrovascular, or peripheral) vascular disease (multisite artery disease). The primary outcome was coronary target lesion failure (TLF), defined as the composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target lesion revascularization at 1-year. Inverse propensity score weighted (IPSW) analysis was performed to address differences in baseline patient and lesion characteristics. RESULTS: Of the 37 198 patients included in the study, 62.3% had no prior known vascular disease, 32.6% had single-territory vascular disease, and 5.1% had multisite artery disease. Patients with known vascular disease were older and were more likely to be men and to have more co-morbidities. After IPSW, the TLF rate incrementally increased with the number of diseased vascular beds (3.16%, 4.44%, and 6.42% for no, single, and multisite artery disease, respectively, P < 0.01 for all comparisons). This was also true for all-cause death (2.22%, 3.28%, and 5.29%, P < 0.01 for all comparisons) and cardiac mortality (1.26%, 1.91%, and 3.62%, P ≤ 0.01 for all comparisons). CONCLUSIONS: Patients with previously known vascular disease experienced an increased risk of adverse cardiovascular events and mortality post-PCI. This risk is highest among patients with multisite artery disease.Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02188355.

Long-term outcomes of patients with normal fractional flow reserve and thin-cap fibroatheroma.

BACKGROUND: The long-term prognostic implications of fractional flow reserve (FFR)-negative lesions hosting vulnerable plaques remain unsettled. AIMS: The aim of this study was to evaluate the association of non-ischaemic lesions hosting optical coherence tomography (OCT)-detected thin-cap fibroatheromas (TCFA) with first and recurrent cardiovascular events during follow-up up to 5 years in a diabetes mellitus (DM) patient population. METHODS: COMBINE OCT-FFR is a prospective, international, double-blind, natural history study. Patients with DM and with ≥1 FFR-negative lesion were classified into 2 groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint (PE) is a composite of cardiac mortality, target vessel-related myocardial infarction (TV-MI), clinically driven target lesion revascularisation (TLR), or unstable angina (UA) requiring hospitalisation during follow-up up to 5 years. RESULTS: Among 390 DM patients (age 67.5±9 years; 37% female) with ≥1 FFR-negative lesion, 292 (74.9%) were TCFA-negative while 98 (25.1%) were TCFA-positive. The PE occurred more frequently in TCFA-positive than in TCFA-negative patients (21.4% vs 8.2%, hazard ratio [HR] 2.89, 95% confidence interval [CI]: 1.61-5.20; p<0.001; 6.42 vs 2.46 events per 100 patient-years, rate ratio [RR] 2.61, 95% CI: 1.38-4.90; p=0.002). Furthermore, when TV-MI, TLR, and UA were treated as recurrent components of the PE, TCFA-positive patients experienced a higher risk of recurrent events (HR 2.89, 95% CI; 1.74-4.80; p<0.001; 13.45 vs 2.87 events per 100 patient-years, RR 4.69, 95% CI: 2.86-7.83; p<0.001). A multivariable analysis identified the presence of TCFA as an independent predictor of the PE (HR 2.76, 95% CI: 1.53-4.97; p<0.001). CONCLUSIONS: OCT-detected TCFA-positive lesions, although not ischaemia-generating, are associated with an increased risk of adverse events during long-term follow-up. CLINICALTRIALS: gov: NCT02989740.

SARS-CoV-2 Positivity, Stent Thrombosis, and 30-day Mortality in STEMI Patients Undergoing Mechanical Reperfusion.

SARS-Cov-2 has been suggested to promote thrombotic complications and higher mortality. The aim of the present study was to evaluate the impact of SARS-CoV-2 positivity on in-hospital outcome and 30-day mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the International Survey on Acute Coronary Syndromes ST-segment elevation Myocardial Infarction (ISACS-STEMI COVID-19 registry. The 109 SARS-CoV-2 positive patients were compared with 2005 SARS-CoV-2 negative patients. Positive patients were older (P = .002), less often active smokers (P = .002), and hypercholesterolemic (P = .006), they presented more often later than 12 h (P = .037), more often to the hub and were more often in cardiogenic shock (P = .02), or requiring rescue percutaneous coronary intervention after failed thrombolysis (P < .0001). Lower postprocedural Thrombolysis in Myocardial Infarction 3 flow (P = .029) and more thrombectomy (P = .046) were observed. SARS-CoV-2 was associated with a significantly higher in-hospital mortality (25.7 vs 7%, adjusted Odds Ratio (OR) [95% Confidence Interval] = 3.2 [1.71-5.99], P < .001) in-hospital definite in-stent thrombosis (6.4 vs 1.1%, adjusted Odds Ratio [95% CI] = 6.26 [2.41-16.25], P < .001) and 30-day mortality (34.4 vs 8.5%, adjusted Hazard Ratio [95% CI] = 2.16 [1.45-3.23], P < .001), confirming that SARS-CoV-2 positivity is associated with impaired reperfusion, with negative prognostic consequences.

Risk of bleeding after percutaneous coronary intervention and its impact on further adverse events in clinical trial participants with comorbid peripheral arterial disease.

BACKGROUND: Both patients with obstructive coronary artery disease (CAD) and patients with peripheral arterial disease (PADs) have an increased bleeding risk. Information is scarce on bleeding in CAD patients, treated with percutaneous coronary intervention (PCI), who have comorbid PADs. We assessed whether PCI patients with PADs have a higher bleeding risk than PCI patients without PADs. Furthermore, in PCI patients with PADs we evaluated the extent by which bleeding increased the risk of further adverse events. METHODS: Three-year pooled patient-level data of two randomized PCI trials (BIO-RESORT, BIONYX) with drug-eluting stents were analyzed to assess mortality and the composite endpoint major adverse cardiac events (MACE: all-cause mortality, any myocardial infarction, emergent coronary artery bypass surgery, or target lesion revascularization). RESULTS: Among 5989 all-comer patients, followed for 3 years, bleeding occurred in 7.7% (34/440) with comorbid PADs and 5.0% (279/5549) without PADs (HR: 1.59, 95%CI: 1.11-2.23, p = 0.010). Of all PADs patients, those with a bleeding had significantly higher rates of all-cause mortality (HR: 4.70, 95%CI: 2.37-9.33, p < 0.001) and MACE (HR: 2.39, 95%CI: 1.23-4.31, p = 0.003). Furthermore, PADs patients with a bleeding were older (74.4 ± 6.9 vs. 67.4 ± 9.5, p < 0.001). After correction for age and other potential confounders, bleeding remained independently associated with all-cause mortality (adj.HR: 2.97, 95%CI: 1.37-6.43, p = 0.006) while the relation of bleeding with MACE became borderline non-significant (adj.HR: 1.85, 95%CI: 0.97-3.55, p = 0.06). CONCLUSION: PCI patients with PADs had a higher bleeding risk than PCI patients without PADs. In PADs patients, bleeding was associated with all-cause mortality, even after adjustment for potential confounders.

Impact of Sex on Clinical Outcomes in Patients undergoing Complex Percutaneous Coronary Angioplasty (from the e-ULTIMASTER Study).

Female gender has been shown to be associated with worse clinical outcomes after percutaneous coronary intervention (PCI). However, the impact of gender on the clinical outcomes of complex PCI is still poorly understood. This study examined the differences in patient and coronary lesion characteristics and longer-term clinical outcomes in male and female patients who underwent complex PCI. This was a sub-analysis of the e-ULTIMASTER study, which was a large, multicontinental, prospective, observational study enrolling 37,198 patients who underwent PCI with the Ultimaster stent. Patients who underwent complex PCI were stratified by gender. The primary outcome was target lesion failure at 12 months, defined as the composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target lesion revascularization at 12 months. A total of 13,623 patients underwent complex procedures, of which 35.7% were women. Women were twice as likely as men to be aged ≥80 years (17.6% vs 9%, p <0.0001) and had a higher prevalence of cardiovascular risk factors. Women had fewer lesions treated than men (1.5 ± 0.8 vs 1.6 ± 0.8, p <0.0001) and fewer stents implanted (2.0 ± 1.1 vs 2.1 ± 1.1, p <0.0001). There was no statistically significant difference in clinical outcomes at 12 months between women and men. Event rates were comparable in women and men for target lesion failure (4.7% vs 4.3%, p = 0.30), target vessel failure (5.1% vs 4.9%, p = 0.73), and cardiac death (1.8% vs 1.7%, p = 0.80).In conclusion, our findings suggest no significant differences in clinical outcomes between women and men who underwent complex PCI.

Morphological characteristics of lesions with thin cap fibroatheroma-a substudy from the COMBINE (OCT-FFR) trial.

AIMS: To study if any qualitative or quantitative optical coherence tomography (OCT) variables in combination with thin cap fibroatheroma (TCFA) patients could improve the identification of lesions at risk for future major adverse cardiac events (MACEs). METHODS AND RESULTS: From the combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) trial database (NCT02989740), we performed a detailed assessment OCT qualitative and quantitative variables in TCFA carrying diabetes mellitus (DM) patients with vs. without MACE during follow-up. MACEs were defined as a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and hospitalization for unstable angina. From the 390 fractional flow reserve (FFR)-negative DM patients, 98 (25.2%) had ≥1 OCT-detected TCFA, of which 13 (13.3%) had MACE and 85 (86.7%) were event-free (non-MACE). The baseline characteristics were similar between both groups; however, a smaller minimal lumen area (MLA) and lower mean FFR value were observed in MACE group (1.80 vs. 2.50 mm2, P = 0.01, and 0.85 vs. 0.89, P = 0.02, respectively). Prevalence of healed plaque (HP) was higher in the MACE group (53.85 vs. 21.18%, P = 0.01). TCFA were predominantly located proximal to the MLA. TCFA area was smaller in the MACE group, while no difference was observed regarding the lesion area. CONCLUSION: Within TCFA carrying patients, a smaller MLA, lower FFR values, and TCFA location adjacent to a HP were associated with future MACE. Carpet-like measured lesion area surface was similar, while the TCFA area was smaller in the MACE arm, and predominantly located proximal to the MLA.

Utility of the ACC/AHA Lesion Classification to Predict Outcomes After Contemporary DES Treatment: Individual Patient Data Pooled Analysis From 7 Randomized Trials.

Background Use of the modified American College of Cardiology (ACC)/American Heart Association (AHA) lesion classification as a prognostic tool to predict short- and long-term clinical outcomes after percutaneous coronary intervention in the modern drug-eluting stent era is uncertain. Methods and Results Patient-level data from 7 prospective, randomized trials were pooled. Clinical outcomes of patients undergoing single lesion percutaneous coronary intervention with second-generation drug-eluting stent were analyzed according to modified ACC/AHA lesion class. The primary end point was target lesion failure (TLF: composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization). Clinical outcomes to 5 years were compared between patients treated for noncomplex (class A/B1) versus complex (class B2/C) lesions. Eight thousand five hundred sixteen patients (age 63.1±10.8 years, 70.5% male) were analyzed. Lesions were classified as A, B1, B2, and C in 7.9%, 28.5%, 33.7%, and 30.0% of cases, respectively. Target lesion failure was higher in patients undergoing percutaneous coronary intervention of complex versus noncomplex lesions at 30 days (2.0% versus 1.1%, P=0.004), at 1 year (4.6% versus 3.0%, P=0.0005), and at 5 years (12.4% versus 9.2%, P=0.0001). By multivariable analysis, treatment of ACC/AHA class B2/C lesions was significantly associated with higher rate of 5-year target lesion failure (adjusted hazard ratio, 1.39 [95% CI, 1.17-1.64], P=0.0001) driven by significantly higher rates of target vessel myocardial infarction and ischemia-driven target lesion revascularization. Conclusions In this pooled large-scale analysis, treating complex compared with noncomplex lesions according to the modified ACC/AHA classification with second-generation drug-eluting stent was associated with worse 5-year clinical outcomes. This historical classification system may be useful in the contemporary era for predicting early and late outcomes following percutaneous coronary intervention.