Percutaneous coronary intervention with ridaforolimus eluting-stents in small vessel coronary artery disease.

INTRODUCTION: The ridaforolimus-eluting stent (RES) system uses a novel cobalt alloy-based coronary stent with a durable elastomeric polymer eluting ridaforolimus. AIM OF STUDY: To assess the safety and efficacy of small diameter (2.25 mm) RES (EluNIR) in small coronary artery disease. METHODS: A prospective, multicenter, single-arm, open-label clinical trial. Clinical follow-up was performed at 30 days, 6 months, and 1 year after the procedure. Target lesions were located in native coronary arteries or bypass graft conduits, with visually estimated diameter of ≥2.25 mm to ≤2.5 mm. The primary endpoint was combined device success, defined as final in-stent residual diameter stenosis <30%, without 30-day major adverse cardiovascular events (MACE). RESULTS: A total of 81 patients were enrolled in the study. Twenty-three patients (28%) had acute coronary syndrome (ACS) at presentation and 37 (46%) had prior myocardial infarction (MI). Most of the target lesions were located in the circumflex coronary artery (44%) and were classified as B2/C grade according to the American Heart Association/American College of Cardiology classification. The final mean minimal lumen diameter, mean reference vessel diameter, and mean residual percent diameter stenosis were 2.0 ± 0.2 mm, 2.3 ± 0.1 mm, and 14 + 6.6%, respectively. The primary endpoint of device success without 30-day MACE was achieved in 98.8% of the patients. Target lesion failure (TLF) at 6 months was 1.2%. Thirty-day and 1-year MACE rates were 1.2% and 2.5%, respectively. CONCLUSION: The EluNIR 2.25 mm stent shows excellent results in small coronary artery disease and adds another tool in the treatment of this complex lesion type.

Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury.

INTRODUCTION: Renal ischemia and reperfusion (IR) injury introduces cellular stress and is the main cause of acute kidney damage. Renal cells exposed to noxious stress induce the expression of the pleiotropic hormone leptin. As we have previously revealed a deleterious stress-related role for leptin expression, these results suggested that leptin is also involved in pathological renal remodeling. The systemic functions of leptin preclude the study of its local effects using conventional approaches. We have therefore designed a method to locally perturb leptin activity in specific tissues without affecting its systemic levels. This study explores whether local anti-leptin strategy is renoprotective in a post-IR porcine kidney model. METHODS: We induced renal IR injury in pigs by exposing kidneys to ischemia and revascularization. Upon reperfusion, kidneys instantly received an intra-arterial bolus of either a leptin antagonist (LepA) or saline solution. Peripheral blood was sampled to assess systemic leptin, IL-6, creatinine, and BUN levels, and postoperative tissue samples were analyzed by hematoxylin and eosin histochemistry and immunohistochemistry. RESULTS: Histology of IR/saline kidneys exhibited extensive necrosis of proximal tubular epithelial cells, as well as elevated levels of apoptosis markers and inflammation. In contrast, IR/LepA kidneys showed no signs of necrosis or inflammation with normal IL-6 and tall-like receptor 4 levels. LepA treatment led to upregulation in mRNA levels of leptin, leptin receptor, ERK1/2, STAT3, and transport molecule Na/H exchanger-3. CONCLUSIONS: Local, intrarenal postischemic LepA treatment at reperfusion prevented apoptosis and inflammation and was renoprotective. Selective intrarenal administration of LepA at reperfusion may provide a viable option for clinical implementation.

Double-blind, placebo-controlled evaluation of biorest liposomal alendronate in diabetic patients undergoing PCI: The BLADE-PCI trial.

BACKGROUND: Diabetes mellitus (DM) is an important predictor of neointimal hyperplasia (NIH) and adverse clinical outcomes after percutaneous coronary intervention (PCI). LABR-312, a novel intravenous formulation of liposomal alendronate, has been shown in animal models to decrease NIH at vascular injury sites and around stent struts. The aim of the Biorest Liposomal Alendronate Administration for Diabetic Patients Undergoing Drug-Eluting Stent Percutaneous Coronary Intervention trial was to assess the safety, effectiveness, and dose response of LABR-312 administered intravenously at the time of PCI withDES in reducing NIH as measured by optical coherence tomography postprocedure in patients with DM. METHODS: Patients with DM were randomized to a bolus infusion of LABR-312 vs placebo at the time of PCI. Dose escalation of LABR-312 in the study arm was given: 0.01 mg, 0.03 mg, and 0.08 mg. The primary endpoint was the in-stent %NIH volume at 9 months as measured by optical coherence tomography. RESULTS: From September 2016 to December 2017, 271 patients with DM undergoing PCI were enrolled; 136 patients were randomized to LABR-312 infusion and 135 patients were randomized to placebo. At 9-month follow-up, no difference was seen in the primary endpoint of %NIH between LABR-312 and placebo (13.3% ± 9.2 vs 14.6% ± 8.5, P = .35). No differences were present with the varying LABR-312 doses. Clinical outcomes at 9 months were similar between groups. CONCLUSIONS: Among patients with DM undergoing PCI with drug-eluting stents, a bolus of LABR-312 injected systematically at the time of intervention did not result in a lower rate in-stent %NIH volume at 9-month follow-up.

The V-LAP System for Remote Left Atrial Pressure Monitoring of Patients With Heart Failure: Remote Left Atrial Pressure Monitoring.

OBJECTIVE: Patients with heart failure (HF) are at an increased risk of hospital admissions. The aim of this report is to describe the feasibility, safety and accuracy of a novel wireless left atrial pressure (LAP) monitoring system in patients with HF. METHODS: The V-LAP Left Atrium Monitoring systEm for Patients With Chronic sysTOlic & Diastolic Congestive heart Failure (VECTOR-HF) study is a prospective, multicenter, single-arm, open-label, first-in human clinical trial to assess the safety, performance and usability of the V-LAP system (Vectorious Medical Technologies) in patients with New York Heart Association class III HF. The device was implanted in the interatrial septum via a percutaneous, trans-septal approach guided by fluoroscopy and echocardiography. Primary endpoints included the successful deployment of the implant, the ability to perform initial pressure measurements and safety outcomes. RESULTS: To date, 24 patients have received implants of the LAP-monitoring device. No device-related complications have occurred. LAP was reported accurately, agreeing well with wedge pressure at 3 months (Lin concordance correlation coefficient = 0.850). After 6 months, New York Heart Association class improved in 40% of the patients (95% CI = 16.4%-63.5%), while the 6-minute walk test distance had not changed significantly (313.9 ± 144.9 vs 232.5 ± 129.9 meters; P = 0.076). CONCLUSION: The V-LAP left atrium monitoring system appears to be safe and accurate.

First-in-Human Evaluation of the Safety and Efficacy of a Novel Stent Positioning Assistance System for Precise Positioning of Coronary Stents.

Objectives: This study was planned for evaluating the safety and efficacy of SPAS (stent positioning assistance system) device in first-in-human procedures. Background: SPAS is a novel device that can be used for improved positioning of coronary stents. Methods: Consecutive patients underwent percutaneous coronary intervention (PCI) with the SPAS device. Device-related adverse and serious adverse events were evaluated in addition to a dedicated questionnaire completed by operators immediately after using SPAS. Results: The SPAS device was deployed in 55 PCI procedures, comprising of heavily calcified lesions (33.3%), totally occluded (7.4%), and severely tortuous vessels (7.4%). In these procedures, nonbifurcation and nonostial (53.7%), bifurcation (22.2%), and edge-to-edge (24.1%) stenting techniques were employed. Analysis of the pooled scores for the five satisfaction-related questions gave an average score of 5.6 ± 1.5, with 40 (75.5%) operators providing an average satisfaction grade of >5; the average operator-rated SPAS device accuracy performance scores exceeded 6 out of 7 (on visual analog score). The time spent for positioning the stent with the SPAS device averaged 41 ± 68.0 seconds. The SPAS device was rated as easy to use (6.1 ± 1.6) and reliable (6.1 ± 1.7). No device-related adverse events were reported. Conclusion: This stent positioning device was evaluated in a consecutive cohort of standard and complex PCI procedures. The device was shown to be safe, easy, and precise to use, both in standard and complex cases.

Contemporary transcatheter aortic valve implantation related thrombocytopenia.

BACKGROUND: Transcatheter aortic valve implantation related thrombocytopenia (TAVI-rTP) is an inevitable phenomenon. However, no study has been performed on TAVI-rTP in the current setting of extended clinical indications combined with technology improvements. METHODS: Patients with severe symptomatic aortic stenosis who underwent transfemoral TAVI, from January 2016 to December 2019 were enrolled. RESULTS: Two-hundred and one consecutive patients (mean age 81.1 ± 7.1 years, 96 men) enrolled. Platelet count was recorded before and after aortic valve implantation. Dropped platelet count (DPC) occurred in all but 11 patients who were included. Two groups were created: DPC <30 and DPC ≥30%. DPC was compared with in-hospital major adverse cardiovascular events. The mean DPC was 26 ± 14%. We found that 67 patients (33.3%) had DPC of more or equal to 30%. In the univariable analysis, the time of the procedure (94.4 ± 32.7 vs 79.4 ± 21.9, p = .002), the amount of the contrast used (125.4 ± 55.4 vs 108.4 ± 44.1, p = .02) and the residual AV gradient (13.3 ± 7.2 vs 14.7, p = .05) were related to a DCP ≥30%. A DPC ≥30% was associated with increased risk of life-threatening/major bleeding (11.9% vs 1.5%, p = .001), major vascular complications (16.4% vs 5.2% p = .009) and death (3.0% vs 0%, p = .044) at 30 days. After multivariable analysis, the factors associated with a higher DPC were time and contrast. CONCLUSION: Contemporary TAVI-rTP in this cohort of patients continues to be a common phenomenon but severe thrombocytopenia is less frequent. Patients developing a DPC ≥30% are associated with poor outcomes at 30 days.

Natural Anti-Endothelial Cell Antibodies in Patients Undergoing Coronary Angiography.

BACKGROUND: Anti-endothelial cell antibodies (AECA) are a known biomarker of endothelial dysfunction and damage in clinical practice, especially in autoimmune disease. OBJECTIVES: To determine the relation between natural AECA levels and prognosis related to coronary artery disease. METHODS: Candidates for coronary angiography were prospectively enrolled. AECA levels were determined by ELISA assay. Mortality was evaluated after more than 5 years follow-up. RESULTS: Of a total 857 patients, 445 had high AECA levels (group 1) and 412 had low levels (< 1 OD unit, group 2). Both groups did not differ in age, sex, or presence of diabetes. The median follow up was 2293 days (76 months). Patients with high AECA levels were more likely to have normal coronary arteries on angiography (21.6% vs. 16.9%, P = 0.047) and less likely to have calcified lesions (19.0% vs. 26.6%, P = 0.028) and lower prevalence of abnormal renal functions (71.1 mg/dl vs. 66.5 mg/dl, P = 0.033). Patients with higher AECA levels had lower mortality levels (20.1% vs. 27.6%, P = 0.006). A logistic regression model demonstrated independent association between lower AECA levels and the presence of coronary atherosclerosis based on angiogram. CONCLUSIONS: After a median of more than 6 years, higher natural AECA levels were associated with less coronary artery disease and lower mortality rates in patients undergoing coronary angiography.

Cardiovascular outcomes following percutaneous coronary intervention with drug-eluting balloons in chronic kidney disease: a retrospective analysis.

BACKGROUND: Chronic kidney disease (CKD) is associated with poorer outcomes following percutaneous coronary intervention (PCI) with drug-eluting stents. Drug-eluting balloons are used for in-stent restenosis and selected cases of de-novo coronary lesions. Little is known regarding the outcomes of individuals with CKD who undergo PCI with drug-eluting balloons. The goal of this study was to assess outcomes of PCI with drug-eluting balloons in individuals with CKD. METHODS: In a retrospective analysis, outcomes of PCI with drug-eluting balloons were compared between 101 patients with CKD and 261 without CKD. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73m2. We compared demographics, procedure data and clinical outcomes in the first and second years following the procedure. RESULTS: Rates of major adverse cardiac events (MACE) and myocardial infarction were higher in patients with than without CKD: 23.8% vs. 13.8%, P < 0.005 and 15.9% vs. 3.8%, P < 0.001, respectively. Rates of target lesion revascularization were similar, 14.9 and 11.5%, respectively, P = 0.4. Shorter duration of dual anti-platelet therapy was observed among patients with than without CKD (10.0 + 3.4 vs. 10.9 + 3.7 months, P < 0.05). First-year hemorrhage episodes were similar in the two groups (0.08 ± 0.4 and 0.03 ± 0.2, respectively, P = 0.2). In a multivariate regression analysis, CKD was associated with increased risks of first year MACE (OR 2.1; 95% confidence interval 1.0-4.3, P < 0.001). CONCLUSIONS: PCI with drug-eluting balloons was associated with increased cardiovascular morbidity and mortality in patients with than without CKD. However, rates of target lesion revascularization were similar in the two groups. Shorter duration of dual anti-platelet therapy was observed in the CKD group.

Percutaneous Coronary Intervention Does Not Lower Cardiovascular Outcomes in Patients with Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of adverse cardiovascular outcomes, in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). However, most studies used bare-metal stents or first-generation drug-eluting stents, and less guideline-directed therapy to reduce cardiovascular risk was reported in CKD patients. This study investigates the impact of moderate-CKD on patients undergoing PCI in the current era. METHODS: Patient level data were pooled from 2 multicenter randomized trials (BIONICS and NIREUS trials) with a near "all-comers" design, comparing PCI with ridaforolimus-eluting stents vs. zotarolimus-eluting stents in patients with CAD. Patients were classified according to the presence or absence of moderate-CKD, defined as creatinine clearance (CrCl) <60 mL/min. We compared baseline characteristics, angiographic findings, and clinical outcomes 1-year post-PCI. RESULTS: 236/2,201 (10.7%) patients had CKD, mean CrCl of 50.3 + 7.8 mL/min. These patients were generally older and more often with hypertension than non-CKD patients, but the use of guideline-directed therapy was similar between the groups. CKD was associated with an increased risk of cardiovascular death (hazard ratio [HR] 6.08; 95% CI 2.11-17.51; p < 0.001), but with a reduced occurrence of repeated revascularization, including ischemia-driven revascularization (HR 0.47; 95% CI 0.24-0.92; p < 0.05). The rate of repeated angiography per severe cardiovascular adverse event was significantly lower in the CKD than the non-CKD group (23/38 [61%] vs. 253/334 [76%], p < 0.05). CONCLUSIONS: Moderate-CKD in patients with CAD was associated with higher rates of all-cause and cardiovascular mortality, yet with a lower risk of revascularization 1-year following PCI. Lack of guideline-directed medical therapy does not explain the adverse outcome of CKD patients.

Effectiveness, benefit harm and cost effectiveness of colorectal cancer screening in Austria.

BACKGROUND: Clear evidence on the benefit-harm balance and cost effectiveness of population-based screening for colorectal cancer (CRC) is missing. We aim to systematically evaluate the long-term effectiveness, harms and cost effectiveness of different organized CRC screening strategies in Austria. METHODS: A decision-analytic cohort simulation model for colorectal adenoma and cancer with a lifelong time horizon was developed, calibrated to the Austrian epidemiological setting and validated against observed data. We compared four strategies: 1) No Screening, 2) FIT: annual immunochemical fecal occult blood test age 40-75 years, 3) gFOBT: annual guaiac-based fecal occult blood test age 40-75 years, and 4) COL: 10-yearly colonoscopy age 50-70 years. Predicted outcomes included: benefits expressed as life-years gained [LYG], CRC-related deaths avoided and CRC cases avoided; harms as additional complications due to colonoscopy (physical harm) and positive test results (psychological harm); and lifetime costs. Tradeoffs were expressed as incremental harm-benefit ratios (IHBR, incremental positive test results per LYG) and incremental cost-effectiveness ratios [ICER]. The perspective of the Austrian public health care system was adopted. Comprehensive sensitivity analyses were performed to assess uncertainty. RESULTS: The most effective strategies were FIT and COL. gFOBT was less effective and more costly than FIT. Moving from COL to FIT results in an incremental unintended psychological harm of 16 additional positive test results to gain one life-year. COL was cost saving compared to No Screening. Moving from COL to FIT has an ICER of 15,000 EUR per LYG. CONCLUSIONS: Organized CRC-screening with annual FIT or 10-yearly colonoscopy is most effective. The choice between these two options depends on the individual preferences and benefit-harm tradeoffs of screening candidates.

Deletion of the Mir-106b~ 25 MicroRNA cluster attenuates atherosclerosis in Apolipoprotein E knockout mice.

BACKGROUND: MicroRNAs are short non-coding RNAs that regulate gene expression. The aim of this study was to gain an understanding of the possible role of the miR-106b~ 25 microRNA cluster in regulating atherosclerosis in mice. METHODS: MiR-106b~ 25 knockout mice were outcrossed into Apolipoprotein E (ApoE) knockout background to generate double knockout mice. At 36 weeks of age, lesion size was evaluated in the aortic sinus by oil-red-O staining. RESULTS: Lesion size was 2-fold smaller in double KO mice in comparison to ApoE KO mice. In addition, collagen staining showed a trend towards a stable plaque phenotype in the double KO mice. Lipid profiling of plasma samples of double KO and ApoE KO mice using FPLC revealed over 2-fold decrease in Very low density lipoprotein (VLDL) cholesterol content and a 50% decrease in low density lipoprotein (LDL) cholesterol content in double KO mice. By using target prediction software, we have identified several possible targets for the miR-106b~ 25 cluster including the VLDL and LDL receptors. We found that upon feeding miR-106b~ 25 KO mice with high fat diet, the expression of LDL and VLDL receptors was higher than in the wild-type mice, suggesting the miR-106b~ 25 cluster regulates atherosclerosis by influencing clearance of VLDL and LDL from the plasma. CONCLUSIONS: We identified the miR-106b~ 25 cluster as a novel regulator of atherosclerosis in ApoE KO mice, presumably by regulating plasma cholesterol levels.

Randomized Comparison of Ridaforolimus- and Zotarolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease: Primary Results From the BIONICS Trial (BioNIR Ridaforolimus-Eluting Coronary Stent System in Coronary Stenosis).

BACKGROUND: The safety and efficacy of a novel cobalt alloy-based coronary stent with a durable elastomeric polymer eluting the antiproliferative agent ridaforolimus for treatment of patients with coronary artery disease is undetermined. METHODS: A prospective, international 1:1 randomized trial was conducted to evaluate in a noninferiority design the relative safety and efficacy of ridaforolimus-eluting stents (RESs) and slow-release zotarolimus-eluting stents among 1919 patients undergoing percutaneous coronary intervention at 76 centers. Inclusion criteria allowed enrollment of patients with recent myocardial infarction, total occlusions, bifurcations lesions, and other complex conditions. RESULTS: Baseline clinical and angiographic characteristics were similar between the groups. Overall, mean age was 63.4 years, 32.5% had diabetes mellitus, and 39.7% presented with acute coronary syndromes. At 12 months, the primary end point of target lesion failure (composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) was 5.4% for both devices (upper bound of 1-sided 95% confidence interval 1.8%, Pnoninferiority=0.001). Definite/probable stent thrombosis rates were low in both groups (0.4% RES versus 0.6% zotarolimus-eluting stent, P=0.75); 13-month angiographic in-stent late lumen loss was 0.22±0.41 mm and 0.23±0.39 mm (Pnoninferiority=0.004) for the RES and zotarolimus-eluting stent groups, respectively, and intravascular ultrasound percent neointimal hyperplasia was 8.10±5.81 and 8.85±7.77, respectively (Pnoninferiority=0.01). CONCLUSIONS: In the present trial, which allowed broad inclusion criteria, the novel RESs met the prespecified criteria for noninferiority compared with zotarolimus-eluting stents for the primary end point of target lesion failure at 12 months and had similar measures of late lumen loss. These findings support the safety and efficacy of RESs in patients who are representative of clinical practice. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01995487.

First-in-Man Experience with a Novel Catheter-Based Renal Denervation System of Ultrasonic Ablation in Patients with Resistant Hypertension.

PURPOSE: To report results of renal denervation (RDN) with the first catheter-based, non-balloon occlusion ultrasonic system in patients with resistant hypertension. MATERIALS AND METHODS: In a multicenter, single-arm trial, 39 patients with resistant hypertension (defined as uncontrolled hypertension while taking ≥ 3 antihypertensive medications) were treated. The cohort consisted of 4 groups: severe resistant hypertension (office systolic blood pressure [OSBP] ≥ 160 mm Hg) treated with a unidirectional catheter (group 1; n = 14); severe resistant hypertension treated with a multidirectional catheter (group 2; n = 18); moderate resistant hypertension (OSBP 140-159 mm Hg) treated with a multidirectional catheter (group 3; n = 5); and recurrent severe resistant hypertension, after an initial response to RF RDN (group 4; n = 2). Blood pressure monitoring was performed for 6 months. RESULTS: Severe adverse events were not noted immediately after the procedure or during follow-up. Treatment time was longer with unidirectional than with multidirectional catheters (36.7 min ± 9.6 vs 11.9 min ± 5.8; P < .001). Mean reductions in office blood pressure (systolic/diastolic) at 1, 3, and 6 months were -26.1/-9.6 mm Hg, -28.0/-9.9 mm Hg, and -30.6/-14.1 mm Hg (P < .01 for all). Per-group analysis showed significant OSBP reduction for groups 1 and 2. Patients with isolated systolic hypertension had a significantly smaller reduction in OSBP after 6 months compared with patients with combined systolic/diastolic hypertension (-16.2 mm Hg ± 18.5 vs -9.9 mm Hg ± 33.4; P < .005). CONCLUSIONS: Use of the RDN system was feasible and safe in this phase I study. Significant blood pressure reductions were observed over 6 months, although less in patients with isolated systolic hypertension.

Renal Sympathetic Denervation System via Intraluminal Ultrasonic Ablation: Therapeutic Intravascular Ultrasound Design and Preclinical Evaluation.

PURPOSE: To assess the safety and performance of a nonfocused and nonballooned ultrasonic (US) catheter-based renal sympathetic denervation (RDN) system in normotensive swine. MATERIALS AND METHODS: RDN with the therapeutic intravascular US catheter was evaluated in 3 experiments: (i) therapeutic intravascular US RDN vs a control group of untreated animals with follow-up of 30, 45, and 90 days (n = 6; n = 12 renal arteries for each group); (ii) therapeutic intravascular US RDN vs radiofrequency (RF) RDN in the contralateral artery in the same animal (n = 2; n = 4 renal arteries); and (iii) therapeutic intravascular US RDN in a recently stent-implanted renal artery (n = 2; n = 4 renal arteries). RESULTS: In the first experiment, therapeutic intravascular US RDN was safe, without angiographic evidence of dissection or renal artery stenosis. Neuronal tissue vacuolization, nuclei pyknosis, and perineuronal inflammation were evident after RDN, without renal artery wall damage. Norepinephrine levels were significantly lower after therapeutic intravascular US RDN after 30, 45, and 90 days compared with the control group (200.17 pg/mg ± 63.35, 184.75 pg/mg ± 44.51, and 203.43 pg/mg ± 58.54, respectively, vs 342.42 pg/mg ± 79.97). In the second experiment, deeper neuronal ablation penetrance was found with therapeutic intravascular US RDN vs RF RDN (maximal penetrance from endothelium of 7.0 mm vs 3.5 mm, respectively). There was less damage to the artery wall after therapeutic intravascular US RDN than with RF RDN, after which edema and injured endothelium were seen. In the third experiment, denervation inside the stent-implanted segments was feasible without damage to the renal artery wall or stent. CONCLUSIONS: The therapeutic intravascular US system performed safely and reduced norepinephrine levels. Deeper penetrance and better preservation of vessel wall were observed with therapeutic intravascular US RDN vs RF RDN. Neuronal ablations were observed in stent-implanted renal arteries.

Distal Radial Fracture Management With an Intramedullary Cage and Fragment Fixation.

PURPOSE: To examine the outcomes associated with the treatment of distal radial fractures with an expandable intramedullary cage and fragment-specific screw fixation. METHODS: A prospective multicenter case series of 100 patients with a fracture of the distal radius treated with the "Cage System" was undertaken. Primary patient outcomes included Disabilities of the Arm, Shoulder, and Hand, Patient-Related Wrist/Hand Evaluation questionnaires, and adverse events associated with the device. Secondary outcomes included wrist range of motion and radiographic findings. RESULTS: Follow-up was performed at intervals of 2 weeks, 4 to 6 weeks, 12 weeks, and 1 year. Ninety-one patients were available for follow-up at 2 weeks, 87 at 4 to 6 weeks, 73 at 3 months, and 61 at 12 months. The mean Disabilities of the Arm, Shoulder, and Hand score at 3 months was 21; at 12 months, it was 9. The mean total Patient-Reported Wrist/Hand Evaluation score at 3 months was 21; at 12 months, it was 11. There were 5 adverse events (5%)-2 involving radial nerve irritation and 3 involving tendon irritation from screws. Four of these 5 patients underwent surgical intervention, a neurolysis in 1 patient and removal of screws in 3. All patients were free of adverse-event symptoms at 3 months' follow-up. Wrist range of motion improved most rapidly in the first 12 weeks following surgery and continued to improve throughout follow-up. The fracture reduction achieved at surgery was maintained throughout the healing process. There was evidence of callus formation at the fracture as early as 2 weeks after surgery with 100% of fractures healed at 3 months. CONCLUSIONS: An expandable intramedullary cage with fragment-specific screw fixation provides maintenance of fracture reduction with a low complication rate. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Thin-capped atheromata with reduced collagen content in pigs develop in coronary arterial regions exposed to persistently low endothelial shear stress.

OBJECTIVE: The mechanisms promoting the focal formation of rupture-prone coronary plaques in vivo remain incompletely understood. This study tested the hypothesis that coronary regions exposed to low endothelial shear stress (ESS) favor subsequent development of collagen-poor, thin-capped plaques. APPROACH AND RESULTS: Coronary angiography and 3-vessel intravascular ultrasound were serially performed at 5 consecutive time points in vivo in 5 diabetic, hypercholesterolemic pigs. ESS was calculated along the course of each artery with computational fluid dynamics at all 5 time points. At follow-up, 184 arterial segments with previously identified in vivo ESS underwent histopathologic analysis. Compared with other plaque types, eccentric thin-capped atheromata developed more in segments that experienced lower ESS during their evolution. Compared with lesions with higher preceding ESS, segments persistently exposed to low ESS (<1.2 Pa) exhibited reduced intimal smooth muscle cell content; marked intimal smooth muscle cell phenotypic modulation; attenuated procollagen-I gene expression; increased gene and protein expression of the interstitial collagenases matrix-metalloproteinase-1, -8, -13, and -14; increased collagenolytic activity; reduced collagen content; and marked thinning of the fibrous cap. CONCLUSIONS: Eccentric thin-capped atheromata, lesions particularly prone to rupture, form more frequently in coronary regions exposed to low ESS throughout their evolution. By promoting an imbalance of attenuated synthesis and augmented collagen breakdown, low ESS favors the focal evolution of early lesions toward plaques with reduced collagen content and thin fibrous caps-2 critical determinants of coronary plaque vulnerability.

Percutaneous Coronary Interventions Using a Ridaforolimus-Eluting Stent in Patients at High Bleeding Risk.

BACKGROUND: Patients treated with percutaneous coronary intervention are often considered to be at a high bleeding risk (HBR). Drug-eluting stents have been shown to be superior to bare-metal stents in patients with HBR, even when patients were given abbreviated periods of dual antiplatelet therapy (DAPT). Short DAPT has not been evaluated with the EluNIR ridaforolimus-eluting stent. The aim of this study was to evaluate the safety and efficacy of a shortened period of DAPT following implantation of the ridaforolimus-eluting stent in patients with HBR. METHODS AND RESULTS: This was a prospective, multicenter, binational, single-arm, open-label trial. Patients were defined as HBR according to the LEADERS-FREE (Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug-Coated Stent versus the Gazelle Bare-Metal Stent in Patients at High Bleeding Risk) trial criteria. After percutaneous coronary intervention, DAPT was given for 1 month to patients presenting with stable angina. In patients presenting with an acute coronary syndrome, DAPT was given for 1 to 3 months, at the investigator's discretion. The primary end point was a composite of cardiac death, myocardial infarction, or stent thrombosis up to 1 year (Academic Research Consortium definite and probable). Three hundred fifteen patients undergoing percutaneous coronary intervention were enrolled, and 56.4% presented with acute coronary syndrome; 33.7% were receiving oral anticoagulation. At 1 year, the primary end point occurred in 15 patients (4.9%), meeting the prespecified performance goal of 14.1% (P<0.0001). Stent thrombosis (Academic Research Consortium definite and probable) occurred in 2 patients (0.6%). Bleeding Academic Research Consortium type 3 and 5 bleeding occurred in 6 patients (1.9%). CONCLUSIONS: We observed favorable results in patients with HBR who underwent percutaneous coronary intervention with a ridaforolimus-eluting stent and received shortened DAPT, including a low rate of ischemic events and low rate of stent thrombosis. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03877848.

Physician-directed patient self-management in heart failure using left atrial pressure: Interim insights from the VECTOR-HF I and IIa studies.

AIMS: Haemodynamic monitoring using implantable pressure sensors reduces the risk of heart failure (HF) hospitalizations. Patient self-management (PSM) of haemodynamics in HF has the potential to personalize treatment, increase adherence, and reduce the risk of worsening HF, while lowering clinicians' burden. METHODS AND RESULTS: The VECTOR-HF I and IIa studies are prospective, single-arm, open-label clinical trials assessing safety, usability and performance of left atrial pressure (LAP)-guided HF management using PSM in New York Heart Association class II and III HF patients. Physician-prescribed LAP thresholds trigger patient self-adjustment of diuretics. Primary endpoints include the ability to perform LAP measurements and transmit data to the healthcare provider (HCP) interface and the patient guidance application, and safety outcomes. This is an interim analysis of 13 patients using the PSM approach. Over 12 months, no procedure- or device-related major adverse cardiovascular or neurological events were observed, and there were no failures to obtain measurements from the sensor and transmit the data to the HCP interface and the patient guidance application. Patient adherence was 91.4%. Using PSM, annualized HF hospitalization rate significantly decreased compared to a similar period prior to PSM utilization (0 admissions vs. 0.69 admissions over 11.84 months, p = 0.004). At 6 months, 6-min walk test distance and the Kansas City Cardiomyopathy Questionnaire overall summary score demonstrated significant improvement. CONCLUSIONS: Interim findings suggest that PSM using a LAP monitoring system is feasible and safe. PSM is associated with high patient adherence, potentially improving HF patients' functional status, quality of life, and limiting HF hospitalizations.

The Additive Effect of Left Ventricular Filling Pressure and Renal Function on Long-Term Prognosis of High-Risk Patients Undergoing Coronary Angiography.

INTRODUCTION: Impaired relaxation is the earliest manifestation of ischemic cascade. Risk factors and renal function abnormalities are associated with coronary disease and diastolic dysfunction as well. We aimed to study the association of noninvasive assessment of left ventricular filling pressures and renal function with mortality in high-risk patients undergoing coronary angiography. PATIENTS AND METHODS: An observational prospective study of 564 consecutive patients undergoing coronary angiography was conducted. The median follow-up was 2,293 days. Patients were categorized into 2 groups according to presence of significant diastolic dysfunction: group 1, 382 patients, with normal and group 2, 182 patients, with elevated filling pressure. Renal insufficiency was determined as calculated glomerular filtration rate <60 mL/min. Patients demographic, clinical, echocardiography, laboratory, and angiographic data were prospectively collected. RESULTS: Fifty-three percent of patients underwent angiography due to acute coronary syndrome (ACS), 85.5% had coronary artery disease, 53.4% had reduced (<50%) left ventricular ejection fraction (LVEF), and 47.4% had abnormal renal function. The mortality during the follow-up period was 30.0%. Patients with elevated filling pressure had significantly higher mortality (50.5% vs. 20.2%, p < 0.0001). Impaired renal failure as well, was associated with higher mortality (48% vs. 15%, p < 0.001). The association remained significant in subgroups of patients with and without ACS and reduced and preserved LVEF. In Cox regression model which combined elevated filling pressure, renal insufficiency, age, diabetes mellitus, hypertension, presence of atrial fibrillation, LVEF, and anemia, elevated filling pressure and renal function impairment were independently associated with higher mortality (HR: 3.717, CI: 1.623-8.475, p < 0.0001 and HR: 0.972, CI: 0.958-0.985, p = 0.0001, respectively). There was an incremental prognostic value of elevated filling pressures and renal function impairment on mortality. CONCLUSIONS: Advanced diastolic dysfunction and impaired renal function are signals toward worse outcomes and are associated with mortality in high-risk patients undergoing coronary angiography.

Control of diabetes mellitus and the risk of neointimal hyperplasia after percutaneous coronary intervention: Post-hoc analysis from the BLADE-PCI trial.

BACKGROUND AND AIMS: Diabetes-mellitus (DM) is associated with increased risk of neointimal hyperplasia (NIH) and restenosis after percutaneous coronary intervention (PCI). We examined a possible association of DM severity at the time of PCI with the development of NIH. METHODS: This post-hoc analysis from the BLADE-PCI randomized, multi-center trial included only patients with DM and baseline data of HbA1c within 14 days prior to the index PCI. All patients were treated with zotarolimus-eluting stents. The primary endpoint was percent of NIH volume at 9 months as evaluated by optical coherence tomography. This endpoint was compared between patients with uncontrolled DM (HbA1c ≥ 7.5%) and controlled DM (HbA1c <7.5%) at the index PCI. RESULTS: The mean percentages of NIH volume were 16.5% ± 9.9 and 12.75% ± 7.9 among patients with baseline HbA1c ≥ 7.5% (n = 74) and <7.5% (n = 102), respectively (p < 0.05). In multivariable analysis, HbA1c ≥ 7.5% was not associated with higher risk of NIH development [95% CI; 2.2 (-0.8, 5.3; p = 0.15)]. Higher HbA1c was not associated with increased risk of NIH at the minimum lumen area site [95% CI; 0.9 (-5.0, 6.7); p = 0.77) or percent stent strut coverage [95% CI; -0.3 (-1.3, 0.6); p = 0.45]. Secondary clinical endpoints including major adverse cardiac and cerebrovascular events, target lesion failure and death were similar between patients with worse and better DM control. CONCLUSIONS: Uncontrolled DM at the time of PCI performed with contemporary drug-eluting stents was not associated with an increased risk of NIH development.