Major Adverse Clinical Events Research Articles

Major Clinical Adverse Events of Breast Implant in the Manufacturer and User Facility Device Experience Database.

Search the Manufacturer and User Facility Device Experience database to collect information on adverse events of breast implant. We analyzed the local complications and the breast implant illness (BII) of silicone breast implants, as well as saline breast implants separately, aim to provide a reference for women who want to breast augmentation. The Manufacturer and User Facility Device Experience database was queried for events reports related to the breast implant between July 1, 2012, and June 30, 2022. Event year and reporting year were summarized. Patient problem was collected and analyzed to distinguish between local complications and BII. A total of 108,728 adverse events in the past 3 years were analyzed, silicone breast implants accounted for 62.1% and saline breast implants accounted for 37.9%. The most common local complication of women receiving silicone breast implants was "Capsular Contracture," accounting for 48.73%. However, the incidence of "capsular contracture" in women who received saline breast implants was only 17.49%. The most common BII was "fatigue/weakness" in both women receiving 2 different breast implants, 17.20% in women receiving silicone breast implants and 24.71% in women receiving saline breast implants. Of note, in all the reports, there was a wide variation in the timing of reporting as compared with the timing of the adverse event. Although the adverse events of breast implant cannot completely be determined from this study, we provide a reference for women who want to get breast implants, so that they can choose breast implants more carefully. In addition, a better understanding of BII may allow them to think further about whether the benefits of breast implants outweigh the risks.

Intravascular Imaging-Guided Versus Coronary Angiography-Guided Complex PCI: A Meta-analysis of Randomized Controlled Trials.

Trials evaluating the role of intravascular imaging in percutaneous coronary intervention (PCI) for complex coronary artery disease have yielded mixed results. This study aimed to compare the outcomes of intravascular imaging specifically intravascular ultrasound (IVUS) with those from conventional coronary angiography in complex PCI. Comprehensive electronic search of MEDLINE, EMBASE, and Cochrane databases was performed until March 2023 for randomized clinical trials (RCTs) comparing intravascular imaging with coronary angiography in patients undergoing complex PCI. Complex PCI was defined per each study, and included PCI for American College of Cardiology/American Heart Association (ACC/AHA) type B2/C lesions, unprotected left main coronary artery disease, or multivessel stenting. The primary study outcome was major adverse clinical events (MACE). The meta-analysis included 10 RCTs with a total of 6615 patients (3576 in the intravascular imaging group and 3039 in the coronary angiography group). The weighted mean-follow up was 28.9months. Compared with coronary angiography, intravascular imaging reduced MACE (8% vs. 13.3%; relative risk [RR] 0.63; 95% confidence interval [CI] 0.54-0.73), cardiac death (RR 0.47; 95%CI 0.31-0.73), definite/probable stent thrombosis (RR 0.48; 95%CI 0.24-0.97), target vessel revascularization (RR 0.62; 95%CI 0.46-0.83), and target lesion revascularization (RR 0.61; 95%CI 0.47-0.79). There was no difference between both groups in all-cause death (RR 0.79; 95%CI 0.53-1.18) and myocardial infarction (RR 0.80; 95%CI 0.61-1.04). In patients undergoing complex PCI, intravascular imaging-specifically IVUS-reduced MACE by decreasing the incidence of cardiac death, stent thrombosis, and target vessel and target lesion revascularization.

Sirolimus-coated balloon in all-comer population of coronary artery disease patients: the EASTBOURNE DIABETES prospective registry

BackgroundThe outcomes of percutaneous coronary intervention (PCI) in diabetic patients are still suboptimal, and it is unclear if diabetic patients might derive a benefit from the use of drug-coated balloons.AimsTo evaluate the impact of diabetes mellitus on the outcomes of patients undergoing PCI with sirolimus-coated balloon (SCB) MagicTouch (Concept Medical, India).MethodsWe conducted a subgroup analysis of the prospective, multicenter, investigator-initiated EASTBOURNE registry, evaluating the performance of MagicTouch SCB in patients with and without diabetes. The study primary endpoint was target lesion revascularization (TLR) at 12-month follow-up. Secondary clinical endpoints were major adverse clinical events (MACE), death, myocardial infarction (MI), and BARC 2–5 bleedings.ResultsAmong 2,083 enrolled patients, a total of 864 suffered from diabetes (41.5%). Patients with diabetes had a numerically higher occurrence of TLR (6.5% vs. 4.7% HR 1.38, 95%CI 0.91–2.08), all-cause death (3.8% vs. 2.6%, HR 1.81, 95%CI 0.95–3.46), and MACE (12.2% vs. 8.9%; HR 1.26 95%CI 0.92–1.74). The incidence of spontaneous MI was significantly higher among diabetic patients (3.4% vs. 1.5%, HR 2.15 95%CI 1.09–4.25); bleeding events did not significantly differ. The overall incidence of TLR was higher among in-stent restenosis (ISR) as compared to de-novo coronary lesions, irrespectively from diabetes status.ConclusionsIn the EASTBOURNE DIABETES registry, diabetic patients treated with the MagicTouch SCB did not have a significant increase in TLR when compared to non-diabetic patients; moreover, diabetic status did not affect the study device performance in terms of TLR, in both de-novo lesions and ISR.

Quantitative Association between Computed-Tomography-Based L1 Skeletal Muscle Indices and Major Adverse Clinical Events Following Percutaneous Coronary Intervention

Sarcopenia is as a non-traditional risk factor for atherosclerotic cardiovascular disease. Further investigation is required to elucidate the prognostic significance of computed tomography (CT)-based sarcopenia assessment in coronary artery disease (CAD). We prospectively enrolled 475 patients, who underwent coronary stent implantation and peri-procedural CT scans within one month. Skeletal muscle index (SMI) was assessed cross-sectionally at the first lumbar vertebra (L1) level. The participants were grouped based on sex-specific L1 SMI quartiles. The primary endpoint was all-cause mortality, and the secondary composite endpoint was major adverse cardiovascular events (MACEs) over a 3-year follow-up period. Three-year all-cause mortality and MACE incidence increased significantly in patients in the lower L1 SMI quartiles compared to those of patients in the higher quartiles (p < 0.001). The individual composite endpoints consistently showed a higher incidence in the lower quartiles of L1 SMI (p < 0.001). In multivariable analysis, the lower L1 SMI quartiles independently predicted 3-year all-cause mortality and MACEs (lowest vs. highest quartiles, respectively: OR 4.90 (95% CI 1.54–15.5), p = 0.007; and OR 12.3 (95% CI 4.99–30.4), p < 0.001). In conclusion, CT-based L1 SMI demonstrated a distinct dose-dependent relationship with future MACEs in CAD patients undergoing percutaneous coronary intervention, thereby enhancing cardiovascular risk stratification.

Stress hyperglycemia ratio and long-term clinical outcome in patients with acute coronary syndrome

Abstract Background Stress hyperglycemia is strongly associated with adverse prognosis in patients with acute coronary syndrome (ACS). Recently, the stress hyperglycemia ratio (SHR- relationship between acute/chronic glycemic values) has been proposed as a better measurement of stress hyperglycemia. Studies on SHR and long-term clinical outcome in ACS are limited. This study aimed to clarify the association between SHR and 3-year adverse clinical events in patients with ACS. Methods We analyzed data of 795 patients admitted to our center for ACS who were enrolled in the PRATO-ACS Registry (ClinicalTrials.gov ID: NCT04087200) and underwent laboratory analyses 1 month after the index event. All patients had undergone early invasive strategy and received high intensity statins during hospitalization and at discharge. Patients were stratified in baseline SHR tertiles: < 0.95, ≥ 0.95 to < 1.17 and ≥ 1.17. The primary end point was 3-year all cause death; secondary end points were major adverse clinical events (MACE) including all-cause death, myocardial infarction or congestive heart failure. The association between SHR and outcome measures was evaluated with Cox proportional analysis expressed by hazard ratio (HR) and 95% confidence intervals (CI). Results With increasing SHR, there was a significant progressive increase in mortality (4.2, 8.3, and 11.7% in the 1st, 2nd, and 3rd tertile, respectively, p= 0.006) and MACE (10.6, 14, and 20.8% in the 1st, 2nd, and 3rd tertile, respectively, p=0.004). Multivariable analysis shows that SHR was an independent predictor of 3-year all-cause death (HR 1.65, 95% CI 1.12-2.4; p= 0.012). Subgroup analysis evidenced that the relationship between SHR and mortality was statistically significant only for patients with poor glycemic control at 1 month follow up (HR 3.4, 95% CI 1.14-10.9, p= 0.02 in the 2nd tertile and HR 3.9, 95% CI 1.3-11.8, p= 0.015 in the 3rd tertile). Conclusion Baseline SHR is significantly associated with 3-year all-cause death and MACE in patients with ACS. However, its prognostic impact is much stronger in patients who do not achieve desired glycemic targets at 1 month after the index event. Therefore, insistent attention to glycemic values is mandatory in ACS patients even after discharge.

Natural course and prognostic impact of lead-related tricuspid regurgitation

Abstract Aim Direct injury from Cardiac Implantable Electrical Device (CIED) leads is one of the most common causes of tricuspid regurgitation (TR), with a reported prevalence up to 40%. Little is known about the natural history of CIED-related TR and the prognostic impact of worsening TR detected at different time points after CIED implantation. Methods The CIED-IT registry retrospectively included patients who underwent CIED implantation in a tertiary referral center in Italy, as long as they had been performed repeated transthoracic echocardiograms (TTE) and at least one chest CT after the implantation. TR severity was graded using a pre-specified 4-class grading scheme: mild, moderate, severe and massive. The primary endpoint for outcome analysis was major adverse clinical events (MACE), defined as the composite of all-cause death or heart failure (HF) hospitalizations. Results 249 patients undergoing CIED implantation from January 2015 to December 2021 were included. Median time to last available TTE was 1593 days (IQR 857-2089). TR prevalence was 71.8% (178/248) at baseline and 88.7% (220/248, p<0.001) at last available TTE. Worsening TR was observed in 48.4% (120/248) of cases. Mean age was 74.5±10.1 years, 35% of patients were females, 45.6% had atrial fibrillation and 41.9% had a LVEF <40%. Baseline RV dysfunction was present in 23.8% of patients, while a worsening RV function was observed in 24.2% of patients with worsening TR and 10.1% of those without worsening TR (p=0.003). Median follow-up time was 4.2 years (IQR: 2.4-5.6). At Kaplan Maier analysis, the cumulative 5-year MACE incidence was 39.4% (95% CI: 30.4-50%) in patients with worsening TR and 18.9% (95% CI: 12.5-28.1%) in those with no worsening TR (Log-Rank p = 0.01). This difference was mainly driven by a higher rate of heart failure hospitalizations in the worsening TR group (36.5% vs, 10 at 5y, Log-Rank p<0.001), while the rate of all-cause death was comparable between the two groups (Log-Rank p=0.313). At multivariable stepwise Cox regression analysis, worsening TR was an independent predictor of both MACE (HR 1.89, 95% CI: 1.15-3.11, p=0.012) and HF hospitalizations (HR 2.77, 95% CI: 1.49-5.16, p=0.001). In a subgroup analysis including patients who also received a 1-year TTE (median time 182 days, IQR: 74-286), worsening TR at last available TTE was still an independent MACE predictor (HR 1.75, 95% CI: 1.0-3.1, p=0.05), while worsening TR at 1y was not (HR 1.66, 95% CI: 0.9-3.06). Conclusions CIED-related TR is a strong determinant of long-term adverse cardiovascular outcomes in patients undergoing CIED implantation. Lead-induced injury is sometimes not evident in the first months after the procedure and might require years to develop clinically significant TR. Serial echocardiographic assessments are therefore pivotal to implement risk stratification, while further knowledge of the pathophysiology of CIED-related TR is required to prevent its occurrence.Kaplan Maier Curves for MACEKaplan Maier curves for HHF

Anatomic vs ischemia-driven strategies for percutaneous coronary revascularization in chronic coronary syndrome: a network meta-analysis

Abstract Background In patients with chronic coronary syndrome (CCS), percutaneous coronary intervention (PCI) stands out as an alternative to optimal medical therapy (OMT). The decision to perform a PCI may be driven either by angiographic evaluation or ischemia assessment, thus depicting different potential strategies which have not yet been compared. Purpose To compare different strategies of percutaneous revascularization (angiography, non-invasive ischemia and coronary physiology (FFR or iFR) guided) in order to identify a potential benefit of PCI depending on the guidance chosen in CCS. Methods Randomized controlled trials (RCTs) comparing OMT vs. PCI-angio guided or vs. PCI guided by non-invasive or invasive ischemia assessment were included and compared via network metanalysis. Major adverse clinical events (MACE), as defined by each included trial, were the primary end point, while cardiovascular (CV) death, myocardial infarction and subsequent revascularization the secondary ones. Results 18 studies, encompassing 17512 patients, were included followed up for a weighted mean of 3,5 years. PCI guided by non-invasive assessment of ischemia entailed a reduced risk of myocardial infarction compared with OMT (HR 0.61:0.37-0.94, CI 95%). This strategy ranked best in preventing CV death. In addition, PCI guided by ischemia defined either invasively or not was associated with a reduced risk of MACE as compared with OMT. iFR and FFR guided approaches showed the highest probability of performing best. Finally, physiology guided PCI ranked best in reducing subsequent urgent revascularizations. Conclusions For patients with CCS, ischemia-guided PCI, either by invasive or noninvasive assessment, resulted in a reduced risk of MACE as compared with OMT. PCI guided by a non-invasive assessment of ischemia reduced risk of myocardial infarction compared to OMT, while PCI guided by iFR or FFR showed the highest probability of reducing the need of subsequent revascularization. These strategies showed the highest probability of reducing MACE and CV death.Bar plot of best treatmentPRISMA diagram and Network Plot

CT pericoronary adipose tissue density predicts coronary allograft vasculopathy and adverse clinical outcomes after cardiac transplantation

Abstract Background Coronary allograft vasculopathy (CAV) is a common cause of heart transplant failure. Coronary Computed Tomography Angiography (CCTA) is used to assess for luminal stenoses in patients with suspected CAV, but additional non-invasive markers are needed to detect early disease and guide the use of treatments that can prevent or slow CAV progression. Purpose We tested the hypotheses that: 1) coronary artery inflammation assessed by pericoronary adipose tissue (PCAT) density and/or total vessel volume-to-myocardial mass ratio (V/M) measured by CCTA could improve the ability to detect CAV in heart transplant patients; and 2) these semi-automated quantitative CCTA metrics would be associated with adverse clinical outcomes. Methods In this retrospective observational cohort study, PCAT density, V/M, and lesion composition were measured in consecutive CCTAs from patients who underwent heart transplantation at a single site between 2010 to 2021. These parameters were incorporated into predictive models for CAV as defined by International Society for Heart & Lung Transplant criteria, and evaluated against long-term clinical outcomes. Results A total of 126 CCTAs were analysed from 94 patients after heart transplant (mean age 49 [SD 14.5] years, 40% female) without CAV (n=86) and with CAV (n=40). PCAT density was higher in transplant patients with CAV (-73.0 HU [SD 9.26]) than without CAV (-77.9 HU [SD 8.23]), and age and sex-matched controls (n=12; -86.19 HU, [SD 5.38]), p<0.001 for both. Unlike patients with atherosclerotic coronary artery disease (n=32), CAV lesions were predominately non-calcified, comprised of mostly fibrous or fibrofatty tissue. V/M was lower in patients with CAV than without (32.4 mm3/g vs. 44.4 mm3/g, p<0.001). PCAT density and V/M improved the ability to predict CAV from AUC 0.78 to 0.87 on receiver operating characteristic analysis (Figure A) when added to donor age and donor/recipient hypertension status (p<0.0001). PCAT density above -66 HU was associated with a greater incidence of all-cause mortality (OR 16.6 95%CI 2.88-109.98, p<0.01; Figure B, box-plot) and the composite endpoint of death, CAV progression, acute rejection, and coronary revascularisation (OR 6.3 95%CI 1.6-32.9, p=0.01) over 5.25 (SD 2.1) years. Conclusions Heart transplant patients with CAV have higher PCAT density and lower V/M than those without. Patients with very high PCAT density on CT had markedly increased incidence of all-cause mortality and major adverse clinical events. These semi-automated metrics could be a useful addition to standard clinical CCTA reporting for diagnosis and monitoring of CAV.Diagnostic Benefit of CTCA MetricsPCAT is predictor of Future Mortality

Association of random glucose to albumin ratio with post-contrast acute kidney injury and clinical outcomes in patients with ST-elevation myocardial infarction

Abstract Background Both glucose and albumin are associated with chronic inflammation, which plays a vital role in post-contrast acute kidney injury (PC-AKI). However, the relationship between the combination of random glucose and albumin in PC-AKI patients remains elusive. Current study aims to explore the relationship between random glucose to albumin ratio (RAR) and the incidence of PC-AKI after percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). Methods We consecutively enrolled STEMI patients who underwent PCI from January,01 2010 to February,28 2020. All patients were categorized into Q1, Q2, and Q3 groups, respectively, based on RAR value ( RAR<8.62; 8.62≤ RAR ≤ 9 .04; 9.04≤ RAR ≤ 9.45). The primary outcome was the incidence of PC-AKI, which is defined as an increase in serum creatinine (SCr) of more than 44.2 mol/L (0.5 mg/dL) from baseline during the inital 48 to 72 hours after contrast exposure. The incidence of major adverse clinical events (MACE) was the second endpoint, which included all-cause mortality, recurrent of myocardial infarction, renal replacement therapy, stroke, and revascularization of target vessel during hospitalization. The association between RAR and PC-AKI was assessed by multivariate logistic regression analysis. Results A total of 2924 patients with STEMI were finally included. The incidence of PC-AKI increased in a stepwise manner with the increasing tertile of RAR (3.2% vs 4.8% vs 10.6%, P<0.001). Multivariate regression analyses demonstrated that RAR(as a continuous variable) was associated with the incidence of PC-AKI (adjusted odds ratio (OR) =1.10, 95% confdence interval (CI) =1.04–1.16, P=0.000) and in-hospital MACE (OR=1.07, 95% CI=1.02–1.14, P=0.012); When RAR was a categorical variable, RAR was related to PC-AKI (Q3 vs. Q1, OR=1.70, 95% CI=1.08–2.67, P=0.021), and in-hospital MACE (Q3 vs. Q1, OR=1.63, 95% CI=1.02-2.60, P=0.041) when analyzed by multivariate regression analyses. Receiver operating characteristic curve analysis showed that RAR exhibited a predictive value for PC-AKI(area under the curve (AUC)=0.666, 95% CI=0.625-0.708, P<0.001), and in-hospital MACE (AUC= 0.662, 95% CI =0.619 - 0.706) . In addition, the AUC of RAR for predicting PC-AKI in the no diabetes subgroup was significantly higher compared to that in the diabetes subgroup (AUC: 0.640 vs. 0.611, P=0.021). Conclusions The high value of RAR was significantly associated with the incidence of PC-AKI and in-hospital MACE after PCI in STEMI patients, and RAR offers a robust predictive value for these outcomes.Figure 1Figure 2

A long-term prognostic factor for cardiovascular risk in patients with chest pain without diabetes mellitus and significant coronary stenosis

Abstract Background Chest pain is the most common symptom of coronary artery disease (CAD); diabetes mellitus (DM) is a well-known single largest risk factor for cardiovascular diseases and survival worldwide. So, the impact of CAD and DM on long-term clinical effects is reported widely. This study aimed to evaluate the long-term prognostic factor for major adverse cardiac and clinical events (MACCE) in patients with chest pain without DM and CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation test. Methods A total of 1,046 patients with chest pain without DM and significant CAD who underwent CAG and ACH tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. All subjects were followed clinically for up to 5 years. Results Coronary spasm (CAS) seems the most common cause of chest pain. However, long-term MACCE of CAS is not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal anti-anginal medication therapy. However, a repeated chest pain remains a problem even with continuous anti-anginal medication therapy. Up to 5-year follows, MACCE has occurred 7.3%, including recurrent angina of 6.9%. Dyslipidemia, mild to moderate CAD, and the use of aspirin/nitrates are associated with long-term MACCE. Conclusions Among the patients with chest pain without DM and significant CAD, the occurring major adverse cardiac events, including death, MI, and de novo CAD, are rare, but recurrent angina is still a challenging problem who had the treatment by anti-anginal medications.

ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions: Design and rationale of the SONAR trial

BackgroundThe percutaneous treatment of calcified coronary lesions remains challenging and is associated with worse clinical outcomes. In addition, coronary artery calcification is associated with more frequent peri-procedural myocardial infarction. Study design and objectivesThe ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions (SONAR) study is an investigator-initiated, prospective, randomized, international, multicenter, open label trial (NCT05208749) comparing a lesion preparation strategy with either shockwave intravascular lithotripsy (IVL) or rotational atherectomy (RA) before drug-eluting stent implantation in 170 patients with moderate to severe calcified coronary lesions. The primary endpoint is difference in the rate of peri-procedural myocardial infarction. Key secondary endpoints include rate of peri-procedural microvascular dysfunction, peri-procedural myocardial injury, descriptive study of IMR measurements in calcified lesions, technical and procedural success, interaction between OCT calcium score and primary endpoint, 30-day and 1-year major adverse clinical events. ConclusionsThe SONAR trial is the first randomized controlled trial comparing the incidence of peri-procedural myocardial infarction between 2 contemporary calcium modification strategies (Shockwave IVL and RA) in patients with calcified coronary artery lesions. Furthermore, for the first time, the incidence of peri-procedural microvascular dysfunction after Shockwave IVL and RA will be evaluated and compared.

Effect of dual antiplatelet therapy prolongation in acute coronary syndrome patients with both high ischemic and bleeding risk: insight from the OPT-CAD study.

In current clinical practice, controversy remains regarding the clinical benefits of prolonged dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients facing high risks of both ischemia and bleeding ("bi-risk") following percutaneous coronary intervention (PCI). This study aimed to investigate the feasibility of identifying a group of bi-risk ACS patients after PCI using the OPT-BIRISK criteria, emphasizing extended DAPT treatment safety and efficacy beyond 12 months in these bi-risk ACS after PCI in real-world conditions. This analysis compared extended DAPT and single antiplatelet therapy (SAPT) at 12-24 months in ACS patients undergoing PCI complicated with both ischemic and bleeding risk as defined by OPT-BIRISK criteria without premature DAPT discontinuation before 9 months or major clinical adverse events within 12 months. This was a post hoc analysis of the Optimal antiPlatelet Antiplatelet Therapy for Chinese Patients with Coronary Artery Disease (OPT-CAD) study. The main research outcome was the incidence of ischemic events within 12-24 months, which was determined as a composite of stroke, myocardial infarction, and cardiac death events. Through propensity score matching (PSM), groups were balanced. For the external validation of the OPT-BIRISK criteria to identify a bi-risk ACS patient, ischemic events, BARC 2, 3, 5 bleeding events, and BARC 3, 5 bleeding events at 5 years were analyzed. The total number of ACS patients analyzed in this analysis was 7,049, of whom 4,146 (58.8%) were bi-risk patients and 2,903 (41.2%) were not. The frequency of ischemic events was significantly different between the two groups at 5 years (11.70% vs. 5.55%, P < 0.001), and the incidence of BARC 2,3,5 bleeding was significantly higher in the bi-risk group (6.90% vs. 4.03%, P < 0.001) than in the non-bi-risk group. Among the bi-risk patients without any clinical adverse events within 12 months that underwent extended DAPT treatment (n = 2,374, 75.7%) exhibited a lower risk of stroke at 12-24 months (1.10% vs. 2.10%, P = 0.036) relative to those that underwent SAPT (n = 763, 24.3%), while bleeding risk did not differ significantly between these groups. PSM cohort analysis results were consistent with those of overall group analyses. In conclusion, the findings showed that using the OPT-BIRISK criteria could help physicians identify ACS patients at a high risk of developing recurrent ischemia and bleeding episodes after PCI. Compared to antiplatelet monotherapy, a strategy of extended DAPT may offer potential benefits in lowering the risk of stroke without carrying a disproportionately high risk of serious bleeding problems among these patients who were event-free after a year of DAPT.

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

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

Use of the Seraph® 100 Microbind® Affinity Blood Filter in an adolescent patient with disseminated adenoviral disease.

The Seraph® 100 Microbind® Affinity Blood Filter (Seraph® 100) is an adjunctive pathogen adsorption device with emergency use authorization for use with extracorporeal therapies to treat COVID-19 infection. Here, we describe the use of Seraph® 100 in a 17-year-old chronically immunosuppressed patient status post deceased donor kidney transplant who presented initially for hematuria, dysuria, and fevers, and was found to have disseminated adenovirus (ADV) infection complicated by nephritis, viral pneumonia, elevated transaminases, and bone marrow suppression. Despite halting immunosuppression for 2weeks, she remained febrile to 40.2°C, with serum ADV counts > 10 million copies/mL (> log 7). Due to concerns about nephrotoxicity from cidofovir treatment, she underwent 2 intermittent treatments with Seraph® 100 to reduce viral load. Fever curve, blood counts, and transaminases stabilized in the days following treatment, and the patient was able to resume her prior immunosuppression regimen without a rebound in viral counts. This adolescent kidney transplant patient with disseminated ADV infection tolerated in-line treatment with Seraph® 100 without major clinical adverse events related to the adsorber, and had resolution of her ADV infection and good clinical recovery.

Sirolimus-Coated Balloon in an All-Comer Population of Coronary Artery Disease Patients: The EASTBOURNE Prospective Registry

BackgroundDrug-coated balloons (DCB) represent 1 of the most promising innovations in interventional cardiology and may represent a valid alternative to drug-eluting stents. Currently, some sirolimus-coated balloons (SCB) are being investigated for several coronary artery disease applications. ObjectivesThis study sought to understand the role of a novel SCB for the treatment of coronary artery disease. MethodsEASTBOURNE (All-Comers Sirolimus-Coated Balloon European Registry) is a prospective, multicenter, investigator-driven clinical study that enrolled real-world patients treated with SCB. Primary endpoint was target lesion revascularization (TLR) at 12 months. Secondary endpoints were procedural success, myocardial infarction (MI), all-cause death, and major adverse clinical events (a composite of death, MI, and TLR). All adverse events were censored and adjudicated by an independent clinical events committee. ResultsA total population of 2,123 patients (2,440 lesions) was enrolled at 38 study centers in Europe and Asia. The average age was 66.6 ± 11.3 years, and diabetic patients were 41.5%. De novo lesions (small vessels) were 56%, in-stent restenosis (ISR) 44%, and bailout stenting occurred in 7.7% of the patients. After 12 months, TLR occurred in 5.9% of the lesions, major adverse clinical events in 9.9%, and spontaneous MI in 2.4% of the patients. The rates of cardiac/all-cause death were 1.5% and 2.5%, respectively. The primary outcome occurred more frequently in the ISR cohort (10.5% vs 2.0%; risk ratio: 1.90; 95% CI: 1.13-3.19). After multivariate Cox regression model, the main determinant for occurrence of the primary endpoint was ISR (OR: 5.5; 95% CI: 3.382-8.881). ConclusionsEASTBOURNE, the largest DCB study in the coronary field, shows the safety and efficacy of a novel SCB in a broad population of coronary artery disease including small vessels and ISR patients at mid-term follow-up. (The All-Comers Sirolimus-Coated Balloon European Registry [EASTBOURNE]; NCT03085823)

Predictive value of elevated neutrophil gelatinase-associated lipocalin levels for assessment of in-hospital adverse outcomes among myocardial infarction patients.

Inflammatory biomarkers are known to rise and have predictive value for adverse outcomes in patients with acute coronary ischemia. One of those biomarkers is neutrophil gelatinase-associated lipocalin (NGAL). To date, only very few studies have assessed the prognostic value of NGAL in this setting. We investigated the prognostic utility of elevated NGAL levels on clinical outcomes among ST-elevation myocardial infarction patients. High NGAL was defined as values within the 4th quartile. Patients were assessed for major in-hospital adverse clinical events (MACE). Multivariable logistic regression and area under the receiver operating characteristic curve (AUC) were used to further evaluate NGAL association for MACE and discrimination ability. A total of 273 patients were included. patients with high NGAL were at increased risk for MACE (62% vs. 19%; odds ratio 6.88, 95% confidence interval, 3.77-12.54, P < 0.001). After propensity score matching, the incidence of MACE was significantly higher in patients with high vs. low NGAL levels (69% vs. 6%, P = 0.002). In multivariable regression, high NGAL level was independently associated with MACE. The discrimination ability of NGAL to identify MACE (AUC 0.823), is significantly better than that of other inflammatory markers. Among ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention, high NGAL levels are associated with adverse outcomes, independent of traditional inflammatory markers.

Phenotypes and outcomes in non-anticoagulated patients with atrial fibrillation: An unsupervised cluster analysis

BackgroundPatients with atrial fibrillation are characterized by great clinical heterogeneity and complexity. The usual classifications may not adequately characterize this population. Data-driven cluster analysis reveals different possible patient classifications. AimsTo identify different clusters of patients with atrial fibrillation who share similar clinical phenotypes, and to evaluate the association between identified clusters and clinical outcomes, using cluster analysis. MethodsAn agglomerative hierarchical cluster analysis was performed in non-anticoagulated patients from the Loire Valley Atrial Fibrillation cohort. Associations between clusters and a composite outcome comprising stroke/systemic embolism/death and all-cause death, stroke and major bleeding were evaluated using Cox regression analyses. ResultsThe study included 3434 non-anticoagulated patients with atrial fibrillation (mean age 70.3±17 years; 42.8% female). Three clusters were identified: cluster 1 was composed of younger patients, with a low prevalence of co-morbidities; cluster 2 included old patients with permanent atrial fibrillation, cardiac pathologies and a high burden of cardiovascular co-morbidities; cluster 3 identified old female patients with a high burden of cardiovascular co-morbidities. Compared with cluster 1, clusters 2 and 3 were independently associated with an increased risk of the composite outcome (hazard ratio 2.85, 95% confidence interval 1.32–6.16 and hazard ratio 1.52, 95% confidence interval 1.09–2.11, respectively) and all-cause death (hazard ratio 3.54, 95% confidence interval 1.49–8.43 and hazard ratio 1.88, 95% confidence interval 1.26–2.79, respectively). Cluster 3 was independently associated with an increased risk of major bleeding (hazard ratio 1.72, 95% confidence interval 1.06–2.78). ConclusionCluster analysis identified three statistically driven groups of patients with atrial fibrillation, with distinct phenotype characteristics and associated with different risks for major clinical adverse events.

Association between the atrial tachyarrhythmia recurrence period and long-term major adverse clinical events following catheter ablation for atrial fibrillation

BackgroundWe previously demonstrated the clinical events in patients who underwent catheter ablation (CA) for atrial fibrillation (AF). Data on the association between the period of atrial tachyarrhythmia (ATA) recurrence after CA and long-term major adverse clinical events (MACE) remain unclear. In this study, we evaluated this issue in patients with systolic impairment (left ventricular ejection fraction < 50%) and heart failure with preserved ejection fraction (HFpEF). MethodsWe retrospectively collected data from 81 patients with systolic impairment and 83 patients with HFpEF who underwent CA for AF at our institution (median follow-up: 4.9 [3.6, 6.6] years). In each group, we compared the cumulative incidence of long-term MACE (since 1 year after CA) between patients with and without ATA recurrence at three follow-up periods (3, 6 months, and 1 year after index CA). We evaluated the period of recurrence, which was the most beneficial predictor of MACE among the periods. ResultsIn the systolic impairment group, the cumulative long-term MACE incidence was significantly higher in patients with ATA recurrence than in those without it within 6 months and 1 year (P = 0.04 and P = 0.01, respectively). Recurrence within 1 year showed the highest feasibility for predicting long-term MACE (area under the curve with 95% confidence interval [CI]:0.73 [0.61–0.84]). However, there was no difference in the incidence of MACE between patients with and without recurrence in a group with HFpEF in each period. ConclusionATA recurrence within 1 year could predict long-term MACE in patients with systolic impairment, but not in patients with HFpEF.

Total Bilirubin Yields Prognostic Information Following a Myocardial Infarction in the Elderly.

Total bilirubin consists of an unconjugated form, solubilized by its binding to albumin, and a conjugated form representing a minor part of the circulating bilirubin. As total bilirubin in physiological concentrations is a powerful antioxidant, its concentration gradient may reflect the health status of an individual, and serve as a prognostic indicator of outcome in primary and secondary cardiovascular disease prevention. The aim of this study was to assess the association between total bilirubin and incident cardiovascular events following a myocardial infarction. Total bilirubin in serum was measured at baseline 2-8 weeks after hospitalization for an MI in 881 patients, aged 70 to 82 years, included in the OMEMI (Omega-3 Fatty acids in Elderly with Myocardial Infarction) study, where patients were followed-up for up to 2 years. The first major adverse clinical event (MACE) was the primary endpoint and consisted of nonfatal MI, unscheduled coronary revascularization, stroke, hospitalization for heart failure or all-cause death. As total bilirubin was non-normally distributed, log-transformed values and quartiles of bilirubin were analyzed using Cox regression models. The median (Q1, and Q3) baseline concentration of bilirubin was 11 (9, and 14) µmol/L, and higher log-transformed concentrations were associated with male sex, lower New York Heart Association (NYHA) class and non-smoking. MACE occurred in 177 (20.1%) patients during the follow-up. Higher concentrations of bilirubin were associated with a lower risk of MACE: HR 0.67 (95%CI 0.47-0.97) per log-unit increase, p = 0.032. Patients in the lowest quartile of bilirubin (<9 µmol/L) had the highest risk with HR 1.61 (95%CI 1.19-2.18), p = 0.002, compared to quartiles 2-4. This association remained significant even after adjusting for age, sex, body mass index (BMI), smoking status, NYHA class and treatment allocation: HR 1.52 (1.21-2.09), p = 0.009. Low concentrations of bilirubin (<9 µmol/L) are associated with increased nonfatal cardiovascular events or death in elderly patients with a recent myocardial infarction.

Management of Retroperitoneal Fibrosis with Endovascular Aneurysm Repair in Patients Refractory to Medical Management

Early diagnosis and treatment of under-recognized retroperitoneal fibrosis (RPF) are essential before reaching the poorly responsive fibrotic stage. Although most patients respond to medical therapy, relapses are common. Open surgery in medically resistant patients is associated with major adverse clinical events. Therefore, we aim to compare the outcomes of endovascular repair in patients with RPF who were refractory to the optimal medical management. This is a single-center longitudinal study of optimal medical therapy (OMT) vs endovascular aneurysm repair (EVAR) in patients with RPF to our tertiary referral vascular center. Seventeen patients were referred to us with peri-aortic RPF over the study period. Eleven received OMT only, whereas six underwent EVAR after the failure of OMT. Eighty-two percent (n = 14) were male, and the mean follow-up was 74.40 ± 58.40 months. Nine (52%) had immunoglobulin G4-related disease (4 OMT vs 5 EVAR). EVAR patients had 100% technical success without perioperative mortality. Furthermore, all the EVAR patients were symptom-free following the intervention. Pre-operative aortic RPF index (maximum peri-aortic soft tissue diameter/maximum aortic diameter) was higher in the EVAR than in the OMT group. However, there was a significant decrement in the aortic RPF index following EVAR (P = .04). EVAR in RPF medical-resistant patients is a valuable option in the armamentarium of nephrologists and rheumatologists. Our study shows that an endovascular intervention provides a promising outcome in RPF/IgG4-RD periaortitis, which is refractory to medical therapy. We recommend further studies to investigate and establish the long-term effectiveness of endovascular repair in RPF.