Impact of preprocedural left ventricular systolic function on the safety and durability of percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is considered less safe in patients with reduced ejection fraction (EF), an impression based on older data. Whether the safety and durability of contemporary PCI are different in patients with reduced EF compared with normal EF patients is unknown. METHODS: Patients from the BIOFLOW II, IV and V clinical trials were grouped as normal EF (≥50%) and reduced EF (30%-50%). Using multivariable logistic regression and cox proportional hazards regression, we determined relations of EF category with procedural safety (a composite of cardiac death, myocardial infarction, stroke and urgent coronary artery bypass grafting within 30 days of PCI) and target lesion failure (TLF; comprising cardiac death, target vessel myocardial infarction, target vessel revascularization within 1 year of PCI) respectively. In sensitivity analyses, we regrouped patients into EF < 45% and ≥55% and repeated the aforementioned analyses. RESULTS: In 1685 patients with normal EF (mean age 65 years; 27% women; mean EF 61%) and 259 with low EF (mean age 64 years; 17% women; mean EF 41%), 101 safety and 148 TLF events occurred. Compared with patients in the normal EF group, those with reduced EF had neither a statistically significant higher proportion of safety events, nor a higher multivariable-adjusted risk for such events. Similarly, patients with reduced EF and normal EF did not differ in terms of TLF event proportions or multivariable-adjusted risk for TLF. The results were similar in sensitivity analyses with EF groups redefined to create a 10% between-group EF separation. CONCLUSION: PCI safety and durability outcomes are similar in patients with mild-moderately reduced EF and normal EF.

The relationship between preoperative blood pressure during anesthetic examinations and pre-intubation blood pressure.

BACKGROUND: There have been few reports showing the relationship between blood pressure (BP) measured at clinics preoperatively and BP measured before anesthetic intubation/induction. The purpose of this study was to examine the relationship between BP measured at different times and settings preoperatively and BP measured before intubation/induction. METHODS: A total of 182 patients who underwent general anesthesia between March 2021 and April 2022 in a university hospital were examined. In addition to self-reported BP asked on an anesthetic examination sheet completed by each patient, BPs were measured three times, before, during, and after preoperative examination by the anesthesiologist. The derived parameter was compared with BP measured before intubation at the time of general anesthesia induction. RESULTS: The systolic BP in the intra-examination period had the most significant correlation with pre-intubation systolic BP (r = 0.5230, p < 0.0001, 95% CI = 0.4050 to 0.6238). On Bland-Altman analysis, the intra-examination systolic BP seemed to be similar and showed better agreement with pre-intubation systolic BP than other measured BPs, with a mean bias of 2.2 mmHg and the narrowest 95% limits of agreement (-33.7 to + 38.1 mmHg). CONCLUSIONS: The preoperative systolic BP value measured during the examination by the anesthesiologist was found to be closely related to pre-intubation systolic BP measured in the operating room. Higher BP during the preoperative examination may be a result of anxiety-induced stress or white-coat hypertension. Measuring BP during the anesthesiologist's examination may be useful for predicting hypertension in the pre-intubation period.

Establishing Monoclonal Gammopathy of Undetermined Significance as an Independent Pre-Disease State of Multiple Myeloma Using Raman Spectroscopy, Dynamical Network Biomarker Theory, and Energy Landscape Analysis.

Multiple myeloma (MM) is a cancer of plasma cells. Normal (NL) cells are considered to pass through a precancerous state, such as monoclonal gammopathy of undetermined significance (MGUS), before transitioning to MM. In the present study, we acquired Raman spectra at three stages-834 NL, 711 MGUS, and 970 MM spectra-and applied the dynamical network biomarker (DNB) theory to these spectra. The DNB analysis identified MGUS as the unstable pre-disease state of MM and extracted Raman shifts at 1149 and 1527-1530 cm-1 as DNB variables. The distribution of DNB scores for each patient showed a significant difference between the mean values for MGUS and MM patients. Furthermore, an energy landscape (EL) analysis showed that the NL and MM stages were likely to become stable states. Raman spectroscopy, the DNB theory, and, complementarily, the EL analysis will be applicable to the identification of the pre-disease state in clinical samples.

Comparison of the diagnostic performance of tryptase and histamine for perioperative anaphylaxis: A multicenter prospective study.

BACKGROUND: Diagnosing perioperative anaphylaxis (POA) is often challenging. Although a guideline recommends measuring tryptase rather than histamine, there is little evidence for this. We aimed to examine the diagnostic performance and appropriate timing of tryptase and histamine measurements for diagnosing anaphylaxis, and the association between Hypersensitivity Clinical Scoring Scheme (HCSS) scores and elevated biomarkers. METHODS: We measured tryptase and histamine levels thrice: 30 min, 2 h, and at least 24 h after an anaphylactic event for patients with suspected anaphylaxis, and at the induction of general anesthesia and 30 min and 2 h after the start of surgery for control patients without a reaction. Absolute values and the magnitude and rate of change from baseline were evaluated. We determined the thresholds of tryptase and histamine levels with the best diagnostic performance and compared their performance. RESULTS: Forty-five patients with perioperative anaphylaxis were included in this study. The control group included 30 patients with uneventful general anesthesia and 12 patients with a suspected but unconfirmed diagnosis of perioperative anaphylaxis. Comparison at the same measurement timings showed that tryptase generally had better diagnostic performance than histamine. Both showed better diagnostic performance when assessed using multiple measurements rather than a single measurement. The best diagnostic performance was seen with the percentage change in the higher tryptase value, whether measured at 30 min or 2 h after anaphylaxis onset, as compared to baseline. However, neither tryptase nor histamine levels correlated with HCSS scores. CONCLUSIONS: Overall, tryptase showed better diagnostic performance than histamine. When multiple tryptase measurements are possible, parameters calculated using two acute phase measurements and the baseline level have better diagnostic performance.

Role of immune cells in the establishment of implantation and maintenance of pregnancy and immunomodulatory therapies for patients with repeated implantation failure and recurrent pregnancy loss.

Background: Immune cells play an important role in the establishment of pregnancy, and abnormalities in the immune system can cause implantation failure and miscarriage. Methods: Previous papers have been summarized and the role of immune cells in reproduction is reviewed. Results: The immune environment in the uterus changes drastically from before implantation to after pregnancy to maintain pregnancy. In allogeneic pregnancies, immature dendritic cells (DCs) that induce immune tolerance from outside the uterus flow into the uterus, and mature DCs that remain in the uterus express programmed cell death ligand 2, which suppresses the immune response. Macrophages are classified into M1-macrophages, which induce inflammation, and M2-macrophages, which suppress inflammation; M1-macrophages are required for luteinization, and M2-macrophages induce the differentiation of endometrial epithelial cells to enable implantation. Regulatory T cells, which suppress rejection, are essential for the implantation and maintenance of allogeneic pregnancies. Implantation failure and fetal loss are associated with decreased numbers or qualitative abnormalities of DCs, macrophages, and regulatory T cells. The clinical usefulness of immunomodulatory therapies in patients with repeated implantation failure and recurrent pregnancy loss has been reported. Conclusion: The provision of individualized medical care in cases of implantation failure or miscarriage may improve clinical outcomes.

Anesthesia management for cesarean section in a woman with chronic renal failure and heart failure: a case report.

INTRODUCTION: Pregnancy in a woman with heart and chronic renal failure can lead to life-threatening complications for both mother and child. Although such cases are often delivered by cesarean section, few reports have described anesthesia methods. CASE PRESENTATION: We encountered a case in which cesarean section was performed using combined spinal and epidural anesthesia for a pregnant woman with chronic renal and heart failure. The 35-year-old Japanese woman had been undergoing hemodialysis for several years. Heart failure symptoms that appeared during pregnancy initially improved with treatments such as increasing hemodialysis, but recurred. She was admitted to the intensive care unit. The initial plan was to deliver the baby after a few weeks, but further progression of heart failure became a concern. After a clinical conference among staff, a cesarean section with combined spinal and epidural anesthesia was scheduled for 24 weeks, 0 days of gestation. The anticoagulant for dialysis was also changed from heparin to nafamostat in preparation for cesarean section. Monitoring was started with central venous and radial artery pressures before induction of anesthesia. Combined spinal and epidural anesthesia was induced and the cesarean section was completed without complications. Surgery was initiated under continuous administration of phenylephrine, which was intended to avoid hypotension due to anesthesia. The hemodynamic and respiratory status of the patient remained stable postoperatively. After the cesarean section, morphine was administered epidurally and the epidural catheter was removed. CONCLUSION: Cesarean section was safely performed for a pregnant woman with renal and heart failure using combined spinal and epidural anesthesia.

A case of pediatric Perthes' disease with unexplained hyperlactatemia at the time of initial surgery and anesthetic management with remimazolam for the subsequent surgery.

BACKGROUND: The causes of perioperative hyperlactatemia vary, but they are generally associated with hypoperfusion. Here, we report the case of a pediatric patient who developed unexplained hyperlactatemia during anesthesia with propofol and sevoflurane, which recurred during a second surgery under anesthesia with remimazolam. CASE PRESENTATION: An 8-year-old boy with Perthes disease and no remarkable past or family history was scheduled for an osteotomy. Anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane and remifentanil. The patient developed lactic acidosis without hemodynamic instability during anesthesia, with a normal lactate/pyruvate ratio after surgery, suggesting a lack of hypoperfusion. We used remimazolam instead of propofol during the second surgery 6 months later, considering the possibility of drug-induced lactic acidosis, including malignant hyperthermia and propofol infusion syndrome, where the unexplained hyperlactatemia recurred. CONCLUSIONS: Distinguishing the causes of hyperlactatemia, particularly in the absence of other symptoms, is challenging. The lactate/pyruvate ratio during episodes of hyperlactatemia can provide insights into the underlying pathology.

Treatment-resistant hiccups during general anesthesia possibly caused by remimazolam: a case report.

BACKGROUND: Previous reports have described hiccups during general anesthesia that were possibly induced by drugs, including benzodiazepines. However, there are few reports of hiccups caused by remimazolam. Case presentation A 75-year-old woman underwent corneal transplantation under general anesthesia with remimazolam. She presented with hiccups once the effects of muscle relaxants used during induction wore off, which persisted even after various treatments, such as the administration of antipsychotic drugs. However, when remimazolam administration was terminated after surgery to awaken the patient, the hiccups stopped and did not recur after extubation. Evaluation of predicted blood levels of remimazolam suggests that higher levels of remimazolam might cause hiccups. CONCLUSION: Remimazolam might induce hiccups during general anesthesia. Anesthesiologists should consider administering muscle relaxants or changing the anesthetic in cases of refractory hiccups under general anesthesia.

CD4+ T cell heterogeneity in gestational age and preeclampsia using single-cell RNA sequencing.

A balance between pro-inflammatory decidual CD4+ T cells and FOXP3+ regulatory T cells (FOXP3+ Tregs) is important for maintaining fetomaternal tolerance. Using single-cell RNA-sequencing and T cell receptor repertoire analysis, we determined that diversity and clonality of decidual CD4+ T cell subsets depend on gestational age. Th1/Th2 intermediate and Th1 subsets of CD4+ T cells were clonally expanded in both early and late gestation, whereas FOXP3+ Tregs were clonally expanded in late gestation. Th1/Th2 intermediate and FOXP3+ Treg subsets showed altered gene expression in preeclampsia (PE) compared to healthy late gestation. The Th1/Th2 intermediate subset exhibited elevated levels of cytotoxicity-related gene expression in PE. Moreover, increased Treg exhaustion was observed in the PE group, and FOXP3+ Treg subcluster analysis revealed that the effector Treg like subset drove the Treg exhaustion signatures in PE. The Th1/Th2 intermediate and effector Treg like subsets are possible inflammation-driving subsets in PE.

Haemodynamic and clinical outcomes at 5 years according to predicted prosthesis-patient mismatch after transcatheter aortic valve replacement.

BACKGROUND/PURPOSE: Although the impact of predicted prosthesis-patient mismatch (PPMP) on outcomes after surgical aortic valve replacement is well established, studies on PPMP in transcatheter aortic valve replacement (TAVR) are limited. This study investigated the effects of PPMp on haemodynamic and 5-year clinical outcomes after TAVR. METHODS/MATERIALS: We analysed 1733 patients who underwent TAVR. PPMp was defined using two different methods: 1) normal reference values of the effective orifice area for each valve type and size indexed to body surface area (PPMp1; n = 1733) and 2) reference values for aortic annulus area or perimeter assessed with pre-procedural computed tomography indexed to body surface area (PPMp2; n = 1227). The primary endpoint was the composite of all-cause death and/or rehospitalisation for heart failure at 5 years. RESULTS: The incidence of PPMp1 was 11.7 % and 0.8 % in moderate and severe cases, respectively. PPMp2 was classified as either moderate (3.8 %) or severe (0 %). Rates of residual mean aortic gradient ≥20 mmHg significantly increased depending on PPMp1 severity (no PPMp1: 3.1 % vs. moderate PPMp1: 26.8 % vs. severe PPMp1: 53.9 %, p < 0.0001) and PPMp2 (no PPMp2: 4.1 % vs. moderate PPMp2: 12.8 %, p = 0.0049). Neither of PPMP methods were associated with the composite outcome in total cohort; however, PPMP1 was significantly related to worse clinical outcomes at 5 years among patients with reduced left ventricular ejection fraction (LVEF) in multivariate analysis (HR: 1.87; 95 % CI: 1.02-3.43). CONCLUSIONS: The impact of PPMP on TAVR clinical outcomes may not be negligible in patients with low LVEF.

Risk Assessment of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Implantation in Patients With Preexisting Right Bundle Branch Block.

Preexisting right bundle branch block (RBBB) is the strongest predictor for permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI). However, the risk assessment for new PPI and effective procedural strategy for preventing new PPI in patients with preexisting RBBB are still unclear. This study stratified the new PPI risk after TAVI and investigated the impact of implantation strategy in a preexisting RBBB cohort. We analyzed 237 patients with preexisting RBBB who underwent TAVI. The primary endpoint was the incidence of new PPI. Multivariate analyses investigating predictors for new PPI were performed. The overall PPI rate was 33.3%. Significant baseline predictors for new PPI were combination of RBBB, left anterior or posterior fascicular block, and first-degree atrioventricular block (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.09 to 5.04), high calcium volume of noncoronary cusp (OR 2.08, 95% CI 1.05 to 4.10), and membranous septum (MS) length <2 mm (OR 2.02, 95% CI 1.09 to 3.75) in the univariate analysis and MS length <2 mm (OR 2.25, 95% CI 1.06 to 4.82) in the multivariate analysis. On the multivariate analysis including procedural variables, predilatation (OR 2.41, 95% CI 1.01 to 5.83), self-expanding valves (Corevalve, Evolut R, and Evolut Pro/Pro+; Medtronic Inc., Minneapolis, Minnesota) or mechanical expanding valves (Lotus/Lotus Edge; Boston Scientifics, Marlborough, Massachusetts) (OR 3.00, 95% CI 1.31 to 6.91), and implantation depth > MS length (OR 4.27, 95% CI 1.81 to 10.08) were significantly associated with new PPI. The incidence of new PPI increased according to the number of baseline predictors (0: 20.9%, 1: 34.3%, and ≥2: 52.0%) and procedural predictors (0: 3.7%, 1: 20.9%, 2: 40.5%, and 3: 60.0%). New PPI risk in a preexisting RBBB subset could be stratified by baseline factors. Device selection and implantation strategy considering MS length could prevent new PPI even in these high-risk population.

Exploiting sweet relief for preeclampsia by targeting autophagy-lysosomal machinery and proteinopathy.

The etiology of preeclampsia (PE), a severe complication of pregnancy with several clinical manifestations and a high incidence of maternal and fetal morbidity and mortality, remains unclear. This issue is a major hurdle for effective treatment strategies. We recently demonstrated that PE exhibits an Alzheimer-like etiology of impaired autophagy and proteinopathy in the placenta. Targeting of these pathological pathways may be a novel therapeutic strategy for PE. Stimulation of autophagy with the natural disaccharide trehalose and its lacto analog lactotrehalose in hypoxia-exposed primary human trophoblasts restored autophagy, inhibited the accumulation of toxic protein aggregates, and restored the ultrastructural features of autophagosomes and autolysosomes. Importantly, trehalose and lactotrehalose inhibited the onset of PE-like features in a humanized mouse model by normalizing autophagy and inhibiting protein aggregation in the placenta. These disaccharides restored the autophagy-lysosomal biogenesis machinery by increasing nuclear translocation of the master transcriptional regulator TFEB. RNA-seq analysis of the placentas of mice with PE indicated the normalization of the PE-associated transcriptome profile in response to trehalose and lactotrehalose. In summary, our results provide a novel molecular rationale for impaired autophagy and proteinopathy in patients with PE and identify treatment with trehalose and its lacto analog as promising therapeutic options for this severe pregnancy complication.

A Novel Sirolimus-Coated Balloon for the Treatment of Femoropopliteal Lesions: The SELUTION SFA Japan Trial.

BACKGROUND: Sirolimus-coated balloons (SCB) for the treatment of femoropopliteal (FP) lesions have not been systematically studied, but initial outcomes from early studies are promising. OBJECTIVES: The authors sought to evaluate the safety and efficacy of the SELUTION SLR SCB, composed of proprietary microreservoir technology combining sirolimus and biodegradable polymer, when used to treat mild-to-moderate FP disease in a Japanese population. METHODS: This multicenter, prospective, single-arm study (SELUTION SFA JAPAN) enrolled 134 patients with FP disease. It was independently adjudicated by an imaging core laboratory and clinical events committee. The primary endpoint was 12-month primary patency, defined as peak systolic velocity ratio ≥2.5 by duplex ultrasound and compared against a prespecified performance goal of 60% based on established angioplasty data. RESULTS: The mean age was 73.8 ± 6.9 years, and 60.3% of patients had diabetes mellitus. The mean lesion length was 127.4 ± 59.7 mm, 17.2% were chronic total occlusions, and 47.8% involved the popliteal artery. Data on 12-month restenosis were available in 127 patients (94.8%). The 12-month primary patency rate was 87.9%, and the freedom from clinically driven target lesion revascularization (CD-TLR) was 97.0% per Kaplan-Meier estimate. The major adverse event rate was 6.7%, driven by 4 CD-TLRs and 5 deaths, none of which were related to the device or procedure. Ankle-brachial index data improved significantly from 0.73 ± 0.16 at baseline to 0.96 ± 0.14 at 30 days postprocedure and was sustained through 12 months (0.94 ± 0.13). CONCLUSIONS: The SELUTION SFA JAPAN trial demonstrated that a novel SELUTION SCB is a safe and effective treatment option for FP disease in symptomatic patients.

Sodium-Glucose Cotransporter-2 Inhibitors Stabilize Coronary Plaques in Acute Coronary Syndrome With Diabetes Mellitus.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are widely used in cardiology and are effective in treating acute coronary syndrome (ACS). Their effects on unstable plaque in patients with ACS remains unclear. This study aimed to examine the effectiveness of SGLT2is in coronary plaque based on optical coherence tomography (OCT) images and the prognosis of ACS with type 2 diabetes mellitus. This retrospective study included 109 patients in the total cohort and 29 patients in the OCT cohort. Based on SGLT2i administration after ACS, the total cohort was categorized into non-SGLT2i (n = 69) and SGLT2i (n = 40) groups. The OCT cohort had 15 and 14 patients in the non-SGLT2i and SGLT2i groups, respectively. The OCT images of unstable plaque were analyzed in nonstented lesions during ACS catheterization and at the 6-month follow-up. The total cohort was assessed after 1 year for major adverse cardiovascular events, including all-cause mortality, revascularization, cerebrovascular disease, and heart failure hospitalization. SGLT2is improved unstable lesions with a significantly thicker fibrous cap (48 ± 15 µm vs 26 ± 24 µm, p = 0.005), reduced lipid arc (-29 ± 12° vs -18 ± 14°, p = 0.028), higher % decrease in total lipid arc (-35 ± 13% vs -19 ± 18%, p = 0.01), and lower major adverse cardiovascular event incidence (log-rank p = 0.023, hazard ratio 4.72 [1.08 to 20.63]) and revascularization rate (adjusted hazard ratio 6.77 [1.08 to 42.52]) than the non-SGLT2i group. In conclusion, SGLT2is can improve the markers of plaque stability and may improve the prognosis in patients with type 2 diabetes mellitus.

1- Versus 3-Month DAPT in Older Patients at a High Bleeding Risk Undergoing PCI: Insights from the XIENCE Short DAPT Global Program.

This analysis aimed to evaluate the effect of 1- versus 3-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in older patients. Data from 3 prospective, single-arm studies (XIENCE Short DAPT Program), including patients with high bleeding risk successfully treated with an everolimus-eluting stent (XIENCE, Abbott) were analyzed. DAPT was discontinued at 1 or at 3 months in patients free from ischemic events and adherent to DAPT. Patients were stratified according to age (≥75 and <75 years). The primary end point was all-cause death or myocardial infarction (MI). The key secondary end point was Bleeding Academic Research Consortium type 2 to 5 bleeding. The outcomes were assessed from 1 to 12 months after index PCI. Of 3,364 patients, 2,241 (66.6%) were aged ≥75 years. The risk of death or MI was similar with 1- versus 3-month DAPT in patients aged ≥75 (8.5% vs 8.0%, adjusted hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69 to 1.30) and <75 years (6.9% vs 7.8%, adjusted HR 0.97, 95% CI 0.60 to 1.57, interaction p = 0.478). Bleeding Academic Research Consortium type 2 to 5 bleeding was consistently lower with 1- than with 3-month DAPT in patients aged ≥75 years (7.2% vs 9.4%, adjusted HR 0.66, 95% CI 0.48 to 0.91) and <75 years (9.7% vs 11.9%, adjusted HR 0.86, 95% CI 0.57 to 1.29, interaction p = 0.737). In conclusion, in patients at high bleeding risk who underwent PCI, patients older and younger than 75 years derived a consistent benefit from 1- compared with 3-month DAPT in terms of bleeding reduction, with no increase in all-cause death or MI at 1 year.

One- versus three-month dual antiplatelet therapy in high bleeding risk patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndromes.

BACKGROUND: A short dual antiplatelet therapy (DAPT) duration has been proposed for patients at high bleeding risk (HBR) undergoing drug-eluting coronary stent (DES) implantation. Whether this strategy is safe and effective after a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains uncertain. AIMS: We aimed to compare the impact of 1-month versus 3-month DAPT on clinical outcomes after DES implantation among HBR patients with or without NSTE-ACS. METHODS: This is a prespecified analysis from the XIENCE Short DAPT programme involving three prospective, international, single-arm studies evaluating the safety and efficacy of 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT among HBR patients after implantation of a cobalt-chromium everolimus-eluting stent. Ischaemic and bleeding outcomes associated with 1- versus 3-month DAPT were assessed according to clinical presentation using propensity score stratification. RESULTS: Of 3,364 HBR patients (1,392 on 1-month DAPT and 1,972 on 3-month DAPT), 1,164 (34.6%) underwent DES implantation for NSTE-ACS. At 12 months, the risk of the primary endpoint of death or myocardial infarction was similar between 1- and 3-month DAPT in patients with (hazard ratio [HR] 1.09, 95% confidence interval [CI]: 0.71-1.65) and without NSTE-ACS (HR 0.88, 95% CI: 0.63-1.23; p-interaction=0.34). The key secondary endpoint of Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding was consistently reduced in both NSTE-ACS (HR 0.57, 95% CI: 0.37-0.88) and stable patients (HR 0.84, 95% CI: 0.61-1.15; p-interaction=0.15) with 1-month DAPT. CONCLUSIONS: Among HBR patients undergoing implantation of an everolimus-eluting stent, 1-month, compared to 3-month DAPT, was associated with similar ischaemic risk and reduced bleeding at 1 year, irrespective of clinical presentation.

First randomised controlled trial comparing the sirolimus-eluting bioadaptor with the zotarolimus-eluting drug-eluting stent in patients with de novo coronary artery lesions: 12-month clinical and imaging data from the multi-centre, international, BIODAPTOR-RCT.

Background: The DynamX™ bioadaptor is the first coronary implant technology with a unique mechanism of unlocking the bioadaptor frame after polymer resorption over 6 months, uncaging the vessel while maintaining a dynamic support to the vessel. It aims to achieve the acute performance of drug-eluting stents (DES) with the advantages of restoration of vessel function. Methods: This international, single blinded, randomised controlled (1:1) trial compared a sirolimus-eluting bioadaptor with a contemporary zotarolimus-eluting stent (DES) in 34 hospitals in Europe, Japan and New Zealand. Patients with de novo coronary lesions and absence of acute myocardial infarction were enrolled from January 2021 to Feburary 2022. The implantation of the bioadaptor followed the standards of DES. An imaging subset of 100 patients had angiographic and intravascular ultrasound assessments, and 20 patients additionally optical coherence tomography. Data collection will continue through 5 years, we herein report 12-month data based on an intention-to-treat population. This trial is registered at ClinicalTrials.gov (NCT04192747). Findings: 445 patients were randomised between January 2021 and February 2022. Device, lesion and procedural success rates, and acute gain were similar amongst the groups. The primary endpoint, 12-month target lesion failure, was 1.8% [95% CI: 0.5; 4.6] (n = 4) versus 2.8% [95% CI: 1.0; 6.0] (n = 6), pnon-inferiority < 0.001 for the bioadaptor and the DES, respectively (Δ-1.0% [95% CI: -3.3; 1.4]). One definite or probable device thrombosis occurred in each group. The 12-month imaging endpoints showed superior effectiveness of the bioadaptor such as in-device late lumen loss (0.09 mm [SD 0.34] versus 0.25 mm [SD 0.39], p = 0.04), and restored compliance and cyclic pulsatility (%mid in-device lumen area change of 7.5% versus 2.7%, p < 0.001). Interpretation: This is the first randomised controlled trial comparing the novel bioadaptor technology against a contemporary DES. The bioadaptor demonstrated similar acute performance and 12-month clinical outcomes, and superior imaging endpoints including restoration of vessel function. Funding: The study was funded by Elixir Medical.

Coronary Intravascular Lithotripsy for Treatment of Severely Calcified Lesions: Long-Term Sex-Specific Outcomes.

Background: Intravascular lithotripsy (IVL) for calcified lesion preparation prior to drug-eluting stent placement has high procedural success and safety, especially in women, whereas other atheroablative approaches are associated with increased procedural complications. We sought to investigate long-term sex-based outcomes of IVL-facilitated stenting. Methods: We performed a patient-level pooled analysis of the single-arm Disrupt CAD III and IV studies. Patient baseline, procedural characteristics, and outcomes were examined according to sex at 30 days and 1 year. The primary end point was major adverse cardiac events (a composite of cardiac death, all myocardial infarction, or target vessel revascularization). Target lesion failure was defined as cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization. Results: A total of 448 patients, 106 (24%) women, were included. Women were older and less likely to be smokers. Women had smaller reference vessel diameters (2.8 mm vs 3.1 mm), shorter lesion length (23.6 mm vs 27.1 mm), and shorter total calcified length (44.4 mm vs 49.3 mm) compared with men. Post-IVL angiographic outcomes and complications were similar between women and men. At 1 year, major adverse cardiac event rates (12.3% vs 13.2%, P = .52) were not different between women and men. There were no differences between women and men (10.4% vs 11.2%; P = .43) in target lesion failure at 1 year. Conclusions: Use of IVL in the treatment of severely calcified lesions is associated with low rates of adverse clinical events and with similar safety and effectiveness in women and men at 1 year.

The Supreme Biodegradable Polymer DES in Acute and Chronic Coronary Syndromes: A PIONEER III Substudy.

Background: The PIONEER III trial demonstrated noninferiority of 12-month target lesion failure (TLF) with the Supreme DES (Sinomed), a thin-strut cobalt-chromium, biodegradable polymer, sirolimus-eluting stent, compared with a durable polymer, everolimus-eluting (XIENCE/PROMUS) stent (DP-EES). The relative safety and effectiveness of the Supreme DES in patients with acute coronary syndromes (ACS) and those with chronic coronary syndromes (CCS) is not known. Methods: PIONEER III was a prospective, multicenter, international, 2:1 randomized trial stratified by clinical presentation. The primary end point was TLF at 12 months (a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization). Results: A total of 1628 patients were enrolled, including 41% of patients with ACS (unstable angina and non-ST-elevation myocardial infarction) randomized to Supreme DES (n = 441) versus DP-EES (n = 232) and 59% of patients with CCS randomized to Supreme DES (n = 645) versus DP-EES (n = 310). Patients with ACS were younger, fewer presented with less diabetes, hypertension, and previous revascularization, but more were current smokers. The primary end point of TLF (6.4% vs 4.4%; P = .1), major adverse cardiac events (8.5% vs 6.5%; P = .16), and stent thrombosis (0.4% vs 0.9%; P = .25) at 12 months were similar in the ACS and CCS groups. There was no difference in TLF at 12 months between Supreme DES and DP-EES among patients with ACS (6.6% vs 6.0%; P = .89) and those with CCS (4.5% vs 4.3%; P = .83); interaction P = .51 for TLF by clinical presentation. Conclusions: Compared with the DP-EES, the Supreme DES seemed safe and effective with a similar TLF at 12 months in both patients with ACS and those with CCS.

Geographic Variations on the Safety and Efficacy of the Supreme Biodegradable Polymer DES: Results From PIONEER III.

Background: The PIONEER III trial showed the 12-month safety and efficacy of the Supreme drug-eluting stent (DES) vs the durable polymer everolimus-eluting stent. We sought to assess whether the characteristics and clinical outcomes of the Supreme DES in PIONEER III were consistent among patients by enrollment location. Methods: This subgroup analysis of the PIONEER III trial compared the characteristics and outcomes of patients recruited from North America, Europe, and Japan and the relative differences in patient outcomes according to the site recruitment volume. Results: From October 2017 to July 2019, 1629 patients were recruited in North America (816, 50.1%), Europe (650, 39.9%), and Japan (163, 10%). Procedural success was achieved in 1556 of 1611 procedures (96.6%), with no difference by the geographic location. Target lesion failure at 12 months for combined groups was observed in 84 of 1629 patients (5.2%), with no significant geographic differences (4.7%, 6.5%, and 2.5%, respectively; P =.08), with similar results in the Supreme DES group alone (4.4%, 6.8%, and 3.7%, respectively, P =.20). Cardiac death at 12 months occurred in 0.4%, 0.2%, and 0.0% (P =.79), target vessel-related myocardial infarction occurred in 2.2%, 4.7%, and 3.7%, (P =.10), and clinically driven target lesion revascularization was required in 2.1%, 3.1%, and 0%, respectively (P =.15). Compared with those from high-recruiting sites, results from low-recruiting sites were similar for target lesion failure, major adverse cardiac events, stent thrombosis, and mortality, with a nonsignificant trend for higher rates of myocardial infarction. Conclusions: Despite regional differences in patient characteristics, the clinical outcomes between Supreme DES and durable polymer everolimus-eluting stent in the PIONEER III trial were not different, supporting the generalizability and robustness of the findings from this multicenter controlled trial.