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The Shock Academic Research Consortium is a multi-stakeholder group, including representatives from the US Food and Drug Administration and other government agencies, industry, and payers, convened to develop pragmatic consensus definitions useful for the evaluation of clinical trials enrolling patients with cardiogenic shock, including trials evaluating mechanical circulatory support devices. Several in-person and virtual meetings were convened between 2020 and 2022 to discuss the need for developing the standardized definitions required for evaluation of mechanical circulatory support devices in clinical trials for cardiogenic shock patients. The expert panel identified key concepts and topics by performing literature reviews, including previous clinical trials, while recognizing current challenges and the need to advance evidencebased practice and statistical analysis to support future clinical trials. For each category, a lead (primary) author was assigned to perform a literature search and draft a proposed definition, which was presented to the subgroup. These definitions were further modified after feedback from the expert panel meetings until a consensus was reached. This manuscript summarizes the expert panel recommendations focused on outcome definitions, including efficacy and safety. [ABSTRACT FROM AUTHOR]

Subclinical leaflet thrombosis (SLT) is characterized on computed tomography (CT) imaging as hypoattenuated leaflet thickening (HALT), reduced leaflet motion (RELM), and hypoattenuation affecting motion (HAM). How antithrombotic regimen type impacts SLT remains poorly understood. We evaluated how antithrombotic regimen type impacts SLT in low-risk subjects following transcatheter aortic valve implantation (TAVI). This substudy is a post hoc analysis of the LRT 1.0 and 2.0 trials to assess SLT in subjects who underwent CT or transoesophageal echocardiogram (TOE) imaging at 30 days, stratified by antithrombotic regimen received (single antiplatelet therapy [SAPT], dual antiplatelet therapy [DAPT], or oral anticoagulation). We also utilized univariable logistic regression modelling to identify echocardiographic predictors of HALT. Rates of HALT, RELM, and HAM were all significantly lower with oral anticoagulation compared to SAPT or DAPT at 30 days (HALT: 2.6% vs 14.3% vs 17.2%, respectively, with p < 0.001; RELM: 1.8% vs 9.6% vs 13.1%, respectively, with p = 0.004; and HAM: 0.9% vs 8.5% vs 9.8%, respectively, with p = 0.011). Additionally, short-term oral anticoagulation was not associated with higher bleeding rates compared to SAPT or DAPT (0.8% vs. 1.8% vs. 3.6%, p = 0.291). The presence of HALT did not significantly impact echocardiographic haemodynamic parameters at 30 days. This is the largest study to date that evaluated the impact of different antithrombotic regimens on SLT in low-risk TAVI patients. Oral anticoagulation was associated with significantly lower rates of SLT at 30 days compared to DAPT or SAPT, and there was no apparent benefit of DAPT over SAPT. [Display omitted] • We compared antithrombotic regimens (OAC, SAPT, DAPT) in low-risk TAVI. • We focused on their impact on subclinical leaflet thrombosis. • OAC showed significantly lower rates of HALT, RELM, and HAM at 30 days post-TAVI. • HALT's presence did not impact echocardiographic hemodynamic parameters. • Short-term anticoagulation was not associated with higher bleeding rates. [ABSTRACT FROM AUTHOR]

Recent randomized studies have broadened the indication of transcatheter aortic valve replacement (TAVR) to also include low-surgical-risk patients. However, the data on self-expanding (SE) and balloon-expandable (BE) valves in low-risk patients remain sparse. The current study is a post hoc analysis of combined data from both LRT 1.0 and 2.0 trials comparing BE and SE transcatheter heart valves. A total of 294 patients received a BE valve, and 102 patients received an SE valve. The 30-day clinical outcomes were similar across both groups except for stroke (4.9% vs. 0.7%, p = 0.014) and permanent pacemaker implantation (17.8% vs. 5.8%, p < 0.001), which were higher in the SE cohort than the BE cohort. No difference was observed in terms of paravalvular leak (≥moderate) between the groups (0% vs. 1.5%, p = 0.577). SE patients had higher aortic valve area (1.92 ± 0.43 mm2 vs. 1.69 ± 0.45 mm2, p < 0.001) and lower mean gradient (8.93 ± 3.53 mmHg vs. 13.41 ± 4.73 mmHg, p < 0.001) than BE patients. In addition, the rate of subclinical leaflet thrombosis was significantly lower in SE patients (5.6% vs. 13.8%, p = 0.038). In this non-randomized study assessing SE and BE valves in low-risk TAVR patients, SE valves are associated with better hemodynamics and lesser leaflet thrombosis, with increased rates of stroke and permanent pacemaker implantation at 30 days; however, this could be due to certain patient-dependent factors not fully evaluated in this study. The long-term implications of these outcomes on structural valve durability remain to be further investigated. LRT 1.0: NCT02628899 LRT 2.0: NCT03557242 • Few studies compared self-expanding vs. balloon-expandable THVs in TAVR. • These were in intermediate- and high-risk patients; data in low-risk are sparse. • We present a post hoc analysis of two trials of younger, low-risk TAVR patients. • Self-expanding THV had better hemodynamics and lower leaflet thrombosis at 30 days. • Balloon-expandable THV had lower stroke and pacemaker implantation at 30 days. [ABSTRACT FROM AUTHOR]

Background: Near-infrared spectroscopy (NIRS) intravascular ultrasound imaging can detect lipid-rich plaques (LRPs). LRPs are associated with acute coronary syndromes or myocardial infarction, which can result in revascularisation or cardiac death. In this study, we aimed to establish the relationship between LRPs detected by NIRS-intravascular ultrasound imaging at unstented sites and subsequent coronary events from new culprit lesions.Methods: In this prospective, cohort study (LRP), patients from 44 medical centres were enrolled in Italy, Latvia, Netherlands, Slovakia, UK, and the USA. Patients with suspected coronary artery disease who underwent cardiac catheterisation with possible ad hoc percutaneous coronary intervention were eligible to be enrolled. Enrolled patients underwent scanning of non-culprit segments using NIRS-intravascular ultrasound imaging. The study had two hierarchal primary hypotheses, patient and plaque, each testing the association between maximum 4 mm Lipid Core Burden Index (maxLCBI4mm) and non-culprit major adverse cardiovascular events (NC-MACE). Enrolled patients with large LRPs (≥250 maxLCBI4mm) and a randomly selected half of patients with small LRPs (<250 maxLCBI4mm) were followed up for 24 months. This study is registered with ClinicalTrials.gov, NCT02033694.Findings: Between Feb 21, 2014, and March 30, 2016, 1563 patients were enrolled. NIRS-intravascular ultrasound device-related events were seen in six (0·4%) patients. 1271 patients (mean age 64 years, SD 10, 883 [69%] men, 388 [31%]women) with analysable maxLCBI4mm were allocated to follow-up. The 2-year cumulative incidence of NC-MACE was 9% (n=103). Both hierarchical primary hypotheses were met. On a patient level, the unadjusted hazard ratio (HR) for NC-MACE was 1·21 (95% CI 1·09-1·35; p=0·0004) for each 100-unit increase maxLCBI4mm) and adjusted HR 1·18 (1·05-1·32; p=0·0043). In patients with a maxLCBI4mm more than 400, the unadjusted HR for NC-MACE was 2·18 (1·48-3·22; p<0·0001) and adjusted HR was 1·89 (1·26-2·83; p=0·0021). At the plaque level, the unadjusted HR was 1·45 (1·30-1·60; p<0·0001) for each 100-unit increase in maxLCBI4mm. For segments with a maxLCBI4mm more than 400, the unadjusted HR for NC-MACE was 4·22 (2·39-7·45; p<0·0001) and adjusted HR was 3·39 (1·85-6·20; p<0·0001).Interpretation: NIRS imaging of non-obstructive territories in patients undergoing cardiac catheterisation and possible percutaneous coronary intervention was safe and can aid in identifying patients and segments at higher risk for subsequent NC-MACE. NIRS-intravascular ultrasound imaging adds to the armamentarium as the first diagnostic tool able to detect vulnerable patients and plaques in clinical practice.Funding: Infraredx. [ABSTRACT FROM AUTHOR]

Background: Transcatheter aortic valve replacement (TAVR) is now the standard of care for patients with symptomatic severe aortic stenosis who are extreme, high, or intermediate risk for surgical aortic valve replacement (SAVR).Objectives: The authors sought to evaluate TAVR in a prospective multicenter trial involving low-risk patients.Methods: The Low Risk TAVR (Feasibility of Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic, Severe Aortic Stenosis) trial was the first U.S. Food and Drug Administration-approved Investigational Device Exemption trial to enroll in the United States. This investigator-led trial was a prospective, multicenter, unblinded, comparison to historical controls from the Society of Thoracic Surgeons (STS) database. The primary endpoint was all-cause mortality at 30 days.Results: The authors enrolled 200 low-risk patients with symptomatic severe aortic stenosis at 11 centers to undergo TAVR. The authors compared outcomes with an inverse probability weighting-adjusted control cohort of 719 patients who underwent SAVR at the same institutions using the STS database. At 30 days, there was zero all-cause mortality in the TAVR group versus 1.7% mortality in the SAVR group. There was zero in-hospital stroke rate in the TAVR group versus 0.6% stroke in the SAVR group. Permanent pacemaker implantation rates were similar between TAVR and SAVR (5.0% vs. 4.5%). The rates of new-onset atrial fibrillation (3.0%) and length of stay (2.0 ± 1.1 days) were low in the TAVR group. One patient (0.5%) in the TAVR group had >mild paravalvular leak at 30 days. Fourteen percent of TAVR patients had evidence of subclinical leaflet thrombosis at 30 days.Conclusions: TAVR is safe in low-risk patients with symptomatic severe aortic stenosis, with low procedural complication rates, short hospital length of stay, zero mortality, and zero disabling stroke at 30 days. Subclinical leaflet thrombosis was observed in a minority of TAVR patients at 30 days. (Feasibility of Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic, Severe Aortic Stenosis [Low Risk TAVR; NCT02628899). [ABSTRACT FROM AUTHOR]

Background: BioFreedom is a polymer- and carrier-free drug-coated stent that delivers Biolimus A9 to the vessel wall. Our purpose was to evaluate the efficacy and safety of this DCS in patients with short-duration dual antiplatelet therapy.Methods: The BioFreedom US IDE feasibility trial was a single-arm, open-label, prospective study of patients requiring stenting of de novo lesions. Patients received 3 months of DAPT, repeat angiography at 9 months, and clinical follow-up at multiple intervals. A subgroup also underwent intravascular ultrasound (IVUS) interrogation. The primary safety end point was major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, target lesion revascularization, or stent thrombosis. The primary efficacy end point, in-stent late lumen loss at 9 months, was compared with a historical control from a first-generation paclitaxel-eluting stent.Results: A total of 72 patients from 10 sites received BioFreedom DCS implanted in 83 de novo lesions. At 9 months, the incidence of composite MACE was 8.4%, and TLR was 1.5%. Short DAPT was safe without occurrence of stent thrombosis. The primary end point of LLL was 0.32±0.53 mm. Paired IVUS analyses comparing postprocedural with 9-month measurements showed low in-stent neointimal volume obstruction (5.39±5.28%) and low neointimal hyperplasia (7.43±8.04 mm3).Conclusions: This study's angiography and IVUS assessments demonstrated that the BioFreedom DCS has anti-restenotic efficacy similar to first-generation DES. In the absence of concerning safety signals, this DCS should be considered effective and safe for patients who require a shorter duration of DAPT. [ABSTRACT FROM AUTHOR]

Myocardial reperfusion injury has been identified as a key determinant of myocardial infarct size in patients undergoing percutaneous or surgical interventions. Although the molecular mechanisms underpinning reperfusion injury have been elucidated, attempts at translating this understanding into clinical benefit for patients undergoing cardiac interventions have produced mixed results. Ischemic conditioning has been applied before, during, or after an ischemic insult to the myocardium and has taken the form of local induction of ischemia or ischemia of distant tissues. Clinical studies have confirmed the safety of differing conditioning techniques, but the benefit of such techniques in reducing hard clinical event rates has produced mixed results. The aim of this article is to review the role of ischemic conditioning in patients undergoing percutaneous and surgical coronary revascularization. [ABSTRACT FROM AUTHOR]

The WATCHMAN left atrial appendage closure (LAAC) technology is a percutaneously delivered permanent cardiac implant placed in the LAA. This device is designed to reduce the risk of stroke and systemic embolism in warfarin-eligible patients with nonvalvular atrial fibrillation. The first circulatory system device panel reviewed the Embolic Protection in Patients With Atrial Fibrillation (PROTECT AF) study in 2009, and a "not approvable" letter was issued by the US Food and Drug Administration (FDA) based on safety concerns. Subsequently, the FDA, collaboratively with the sponsor, designed a new Prospective Randomized Evaluation of the WATCHMAN LAAC Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy (PREVAIL) trial to address the earlier study limitations. A second panel was convened in December 2013 to review the results of PREVAIL and additional long-term follow-up data from PROTECT AF. The second panel voted favorably 13 to 1 that the benefits of the WATCHMAN LAAC therapy do outweigh the risks for use in patients who meet the criteria specified in the proposed indication. Subsequently, and during the premarket approval review, updated data from the PREVIAL study revealed more ischemic strokes in the WATCHMAN group, corresponding to a total of 13 ischemic strokes in the WATCHMAN group versus 1 in the control group. As a result of these strokes, the FDA called for a third panel to assess the benefit-risk profile of the WATCHMAN device. This summary aims to describe the discussions and recommendations made during the panel meetings. [ABSTRACT FROM AUTHOR]

The Lutonix® drug coated balloon (DCB) is a combination device composed of a standard percutaneous angioplasty balloon coated with paclitaxel. Depending on the balloon size, a dose density of 2 μg/mm 2 yields a variable total dose raging from 1.5 mg to 3.8 mg. This drug coated balloon aims to provide improved patency rates in patients with symptomatic femoropopliteal de novo or restenotic atherosclerotic disease. On June 12, 2014, the Food and Drug Administration's (FDA) Circulatory System Devices Panel reviewed the Lutonix DCB premarket approval application (PMA). This PMA application was primarily based on data from the pivotal randomized, controlled and multicenter clinical trial, which compared the Lutonix DCB with PTA. This summary aims to describe the discussions and recommendations made by the advisory panel during the meeting. Based on the Panel's recommendations, it is possible that the FDA will approve this device. [ABSTRACT FROM AUTHOR]

Major vascular complications after transcatheter aortic valve replacement (TAVR) are a pertinent issue and associated with increased morbidity and mortality. We herein describe a case of acute limb ischemia following the administration of protamine sulfate (PS) that was administered to mitigate a bleeding complication post-failure of a vascular access closure device. PS should be used cautiously for the prevention or management of bleeding-site complications following TAVR. The patient described in this case has consented to having his case described in this manuscript. • Major vascular complications after TAVR are associated with increased mortality. • Acute limb ischemia followed administration of protamine sulfate (PS). • PS was given to mitigate bleeding post-vascular access closure device failure. • PS should be used cautiously to manage bleeding-site complications post-TAVR. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including the use of drug-coated balloons (DCBs) in treating coronary heart disease, the effectiveness of drugs, and the frequency of restenosis and target lesion revascularization (TLR).

Abstract: Over the last decade, the introduction of drug-eluting stents has dramatically reduced restenosis and the need for repeat revascularization after implantation of metallic stents. Numerous concerns still remain, however, because of their permanent nature. Thus, the concept of bioresorbable temporary scaffolds composed of biocompatible materials has emerged as a potential alternative to permanent metal stents. Here we focus on metal alloys & discuss preclinical and clinical experiences with bioresorbable metal scaffolds. [Copyright &y& Elsevier]

Background: Live case demonstration as an educational tool is widely used to rapidly and effectively disseminate information on surgical and interventional techniques. The risks and benefits of live case transmission for investigational devices, however, are in question. Methods: Transcatheter Aortic Valve Intervention-Live Transmission (VERITAS) is a case–control study of 60 patients from 5 centers who were treated with transcatheter aortic valve replacement (TAVR) during live- or recorded transmission; of which 42 have matched Control subjects from five sites. Case and Control subjects were matched by valve type, access strategy (Edwards SAPIEN transfemoral, Edwards SAPIEN transapical, CoreValve transfemoral), Society of Thoracic Surgeons (STS) score, date of TAVR procedure, and primary operator. Results: The Case and Control groups’ baseline characteristics were similar, with average ages of 84 and 82 years, and STS scores of 6.54±3.22 and 6.46±3.20, respectively. The number of operators, fluoroscopy time, contrast volume and length of hospital stay were also similar between groups. Overall, 91.7% of the cases had TAVR via a transfemoral approach; 72% of these patients received a closure device. The final valve position was adequate in 91.2% of the Case patients and in 97% of the Control patients, with no cases of valve migration or coronary obstruction. The Case patients had longer procedure times (130.2±50.6 versus 100.6±43.7min; p=0.006). The Valve Academic Research Consortium in-hospital complications were similar between groups. Four Case patients and 1 Control patient required additional valve implantation. Conclusion: Data support the notion that live transmission of TAVR procedures, when performed by experienced operators, can be done safely with similar outcomes when compared to non-transmitted cases. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to evaluate the impact of chronic lung disease (CLD) on outcomes of severe aortic stenosis patients across all treatment modalities. Background: Outcomes of patients with CLD undergoing transcatheter aortic valve replacement (TAVR) have not been systematically examined. Methods: All patients who underwent TAVR in the PARTNER (Placement of AoRTic TraNscathetER Valve) trial, including the continued access registry (n = 2,553; 1,108 with CLD), were evaluated according to CLD clinical severity. Additionally, outcomes of CLD patients included in the randomization arms of the PARTNER trial were compared: Cohort A patients (high-risk operable) treated by either TAVR (n = 149) or surgical aortic valve replacement (SAVR); (n = 138); and Cohort B patients (inoperable) treated by either TAVR (n = 72) or standard therapy only (n = 95). Results: Among all TAVR-treated patients, at 1-year follow-up, patients with CLD had higher mortality than those without it (23.4% vs. 19.6%, p = 0.02). Baseline characteristics of CLD patients who underwent TAVR were similar to respective controls. In Cohort A, 2-year all-cause death rates were similar (TAVR 35.2% and SAVR 33.6%, p = 0.92), whereas in Cohort B, the death rate was lower after TAVR (52.0% vs. 69.6% after standard therapy only, p = 0.04). Independent predictors for mortality in CLD patients undergoing TAVR included poor mobility (6-min walk test <50 m; hazard ratio: 1.67, p = 0.0009) and oxygen-dependency (hazard ratio: 1.44, p = 0.02). Although CLD patients undergoing TAVR have worse outcomes than patients without CLD, TAVR is better in these patients than standard therapy and is similar to SAVR. Conclusions: Although patients with CLD undergoing TAVR had worse outcomes than patients without CLD, TAVR performed better in these patients than standard therapy and was similar to SAVR. However, CLD patients who were either poorly mobile or oxygen-dependent had poor outcomes. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894) [Copyright &y& Elsevier]

Abstract: Despite a wide range of drug treatment for hypertension, resistant hypertension rates remain high. The Symplicity™ Renal Denervation System (Medtronic, Santa Rosa, CA), which creates renal nerve denervation, has shown initial success in lowering blood pressure among patients with resistant hypertension. Given the enormous market for this treatment approach, an estimated two dozen other companies are pursuing technologies with alternative approaches. Despite this fact, very little has been published on preclinical and clinical experience with these new devices. The current review summarizes the most prominent technologies in the pipeline and provides insight into the mechanism of action, preclinical, and clinical experience with these new devices. [Copyright &y& Elsevier]

We aimed to determine the optimal adjunctive anticoagulation regimen for percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS) initially treated with fondaparinux. The optimal adjunctive anticoagulation regimen for PCI in these patients is unclear. In this open-label, prospective, randomized, multicenter pilot study, we compared treatment with unfractionated heparin (UFH) versus bivalirudin in patients with non-ST-segment elevation ACS initially treated with fondaparinux and undergoing early invasive strategy. The randomized population consisted of 100 patients (62.7 ± 12.7 years, 68% men), all of whom were on clopidogrel. During the angioplasty, patients were randomized to either bivalirudin or UFH therapy in a 1:1 fashion. Baseline clinical and angiographic characteristics were similar except for a higher body mass index in the UFH group (29.4 ± 4.7 vs. 27.3 ± 4.2, P = 0.02). Major bleeding was the primary outcome; a major bleeding event was documented in only 1 patient from the bivalirudin group (2%) and in none from the UFH group (P = 0.49). There was no death, Q-wave MI, or acute revascularization in either group. There was no documentation of stent thrombosis, reinfarction, and catheter thrombus. Data from this prospective, multicenter pilot study suggest that bivalirudin, compared to standard-dose UFH, has a similar safety profile in terms of peri-PCI bleeding and thrombotic events and can be used safely in ACS patients initially treated with upstream fondaparinux who undergo PCI. (J Interven Cardiol 2013;26:107-113) [ABSTRACT FROM AUTHOR]

Objectives: FIRST (Fractional Flow Reserve and Intravascular Ultrasound Relationship Study) aimed to determine the optimal minimum lumen area (MLA) by intravascular ultrasound (IVUS) that correlates with fractional flow reserve (FFR) and to assess the correlation between virtual histology IVUS and FFR for intermediate coronary lesions. Background: FFR is considered the gold standard for assessing intermediate coronary lesions. Measurements of ≤0.8 are considered clinically significant and indicative of physiological ischemia. Methods: FIRST is a multicenter, prospective, international registry of patients with intermediate coronary lesions, defined as 40% to 80% stenosis by angiography. In total, 350 patients (367 lesions) were enrolled at 10 U.S. and European sites. Patients were followed through hospital discharge. Results: Overall, an MLA <3.07 mm2 (64.0% sensitivity, 64.9% specificity, area under curve [AUC] = 0.65) was the best threshold value for identifying FFR <0.8. The accuracy improved when reference vessel–specific analyses were performed. An MLA <2.4 mm2 (AUC = 0.66) was best for reference vessel diameters <3.0 mm, an MLA <2.7 mm2 (AUC = 0.71) for reference vessel diameters of 3.0 to 3.5 mm, and an MLA <3.6 mm2 (AUC = 0.68) for reference vessel diameters >3.5 mm. FFR correlated with plaque burden (r = −0.220, p < 0.001) but not with other plaque morphology. Conclusions: Anatomic measurements by IVUS show a moderate correlation with the FFR values. The optimal cutoff for an MLA to FFR <0.8 is vessel dependent. Plaque morphology characteristics do not correlate with FFR. The utility of IVUS MLA as an alternative to FFR to guide intervention in intermediate lesions may be limited in accuracy and should be tested clinically. (Fractional Flow Reserve and Intravascular Ultrasound Relationship Study [FIRST]; NCT01153555) [Copyright &y& Elsevier]

Abstract: Percutaneous coronary intervention of aorto-ostial lesions is associated with high rates of major adverse cardiovascular events. Precise implantation of coronary stents in the ostium is important in order to prevent adverse clinical outcomes. The presented case demonstrates a simple technique to accurately position a stent during aorto-ostial percutaneous coronary intervention. [Copyright &y& Elsevier]

Registry Experience at the Washington Hospital Center, DES - Taxus Liberte Versus Xience V (REWARDS TLX) is a physician-initiated, retrospective, real-world, multicenter, observational study for all patients >18 years of age subjected to percutaneous coronary intervention with everolimus-eluting stents (EESs) or paclitaxel-eluting stents (PESs). Outcomes of patients receiving a TAXUS Liberté or XIENCE V drug-eluting stent were compared. Baseline clinical, procedural, and follow-up data at 12 months were collected from 10 clinical centers by an electronic data capture system. The study''s primary end point was major adverse cardiac events: a composite of all-cause death, Q-wave myocardial infarction, target vessel revascularization, and stent thrombosis. The trial is registered with http://www.clinicaltrials.gov (NCT01134159). Data were entered for 1,195 patients (PES, n = 595; EES, n = 600). Baseline clinical characteristics were similar except for higher dyslipidemia, systemic hypertension, and family history of coronary artery disease in the EES group. In-hospital outcome was similar between groups, with an overall in-hospital stent thrombosis rate of 0.2%. The primary end point at 12 months was similar (EES 7.8% vs 10.8%, p = 0.082). Overall stent thrombosis rate was lower in the EES group (0.3% vs 1.2%, respectively, p = 0.107); however, target lesion revascularization was similar (PES, hazard ratio 1.46, 95% confidence interval 0.98 to 2.19, p = 0.064). There was no difference in overall mortality between groups. In conclusion, second-generation EESs and PESs demonstrated similar efficacy and safety profiles for broadened patient and lesion subsets compared to a selected population from the pivotal trials. However, for composite efficacy and safety end points, EESs outperformed second-generation PESs. [Copyright &y& Elsevier]

The author reflects on the importance of metallic stents in cardiology field. He mentions that metallic stents has overcome the shortcoming of balloon angioplasty and has also reduced restenosis occurrence rate. He also includes that metal stents has became the default device for treatment of every lesion in coronary artery.

Data from randomized clinical trials have shown the safety and efficacy of the XIENCE V in selected populations. However, limited data are available comparing the XIENCE V to the first-generation CYPHER sirolimus-eluting stent. This study aimed to assess the long-term safety and clinical efficacy of the XIENCE V everolimus-eluting stent compared to first-generation stents in an unselected patient population. This retrospective analysis included 6,069 patients treated with CYPHER, TAXUS, and XIENCE stents from 2003 to 2009 at our institution. The patients were followed up for ≥1 year after the index procedure. The baseline characteristics were generally comparable among the 3 groups, with the exception of a significantly greater prevalence of diabetes mellitus, systemic hypertension, and a history of angioplasty and coronary bypass surgery among the XIENCE patients. The XIENCE patients also had a twofold greater rate of type C lesions. One-year follow-up data were available for 82% of the patients. The 1-year major adverse cardiovascular events rate was 9.3% for the XIENCE stent versus 9.8% for the CYPHER stent and 11.5% for the TAXUS stent (p = 0.11). Mortality was lower in the XIENCE group than in the CYPHER and TAXUS groups (3.6% vs 4.9% vs 7.2%, respectively, p <0.001), and target lesion revascularization was similar (5.9% vs 5.2% vs 5.6%, respectively; p = 0.34). Stent thrombosis was lower in the XIENCE patients (0.2% vs 1.2% vs 0.7%, p = 0.007). In conclusion, in a contemporary United States clinical practice with an unselected patient population, use of the XIENCE V stent was associated with an improved safety profile and reduction of all-cause mortality and stent thrombosis compared to first-generation drug-eluting stents. The XIENCE V failed to demonstrate superiority for overall major adverse cardiovascular events, Q-wave myocardial infarction, and revascularization rates. [ABSTRACT FROM AUTHOR]

The article provides a summary of the discussions and recommendations made during the Circulatory System Devices Advisory Panel meeting on transcatheter aortic valve system held by the U.S. Food and Drug Administration (FDA) on July 20, 2011, along with some insights regarding the clinical use of the Edwards SAPIEN transcathether heart valve (THV) in a postapproval era. The proposed indication of use of the THV are discussed. Also included is the efficacy assessment of the Edwards THV.

Abstract: Platelets play a pivotal role in normal hemostasis, and derangement of their function can lead to hemorrhage or thrombosis. While progress has been made in elucidating the molecular mechanisms leading to platelet adhesion, aggregation, shape change and secretion, clinically useful tests of platelet function have lagged. A number of dedicated platelet function instruments that are much simpler to use and are now utilized as point-of-care (POC) instruments have now become available. Some instruments have been incorporated into routine clinical use and can be utilized not only as general screening tests of platelet function but as monitors of antiplatelet therapy and to potentially assess both risk of bleeding and/or thrombosis. Some of the factors that differentiate these tests are sample volume requirements, the use of whole blood, the presence of shear, POC status, need for a technician and expense. The following is a review of some of the commonly used tests of platelet function, along with their advantages and disadvantages. The tests and pertinent instruments described are based on aggregation, shear stress platelet contribution to clot strength, flow cytometry and serum and urinary thromboxane metabolites. [Copyright &y& Elsevier]

Objectives: This study aimed to determine whether serial autologous infusions of selective high-density lipoprotein (HDL) delipidated plasma are feasible and well tolerated in patients with acute coronary syndrome (ACS). Background: Low HDL is associated with increased risk of cardiovascular disease. Plasma selective delipidation converts αHDL to preβ-like HDL, the most effective form of HDL for lipid removal from arterial plaques. Methods: ACS patients undergoing cardiac catheterization with ≥1 nonobstructive native coronary artery atheroma were randomized to either 7 weekly HDL selective delipidated or control plasma apheresis/reinfusions. Patients underwent intravascular ultrasound (IVUS) evaluation of the target vessel during the catheterization for ACS and up to 14 days following the final apheresis/reinfusion session. 2-D gel electrophoresis of delipidated plasmas established successful conversion of αHDL to preβ-like HDL. The trial was complete with 28 patients randomized. Results: All reinfusion sessions were tolerated well by all patients. The levels of preβ-like HDL and αHDL in the delipidated plasma converted from 5.6% to 79.1% and 92.8% to 20.9%, respectively. The IVUS data demonstrated a numeric trend toward regression in the total atheroma volume of −12.18 ± 36.75 mm3 in the delipidated group versus an increase of total atheroma volume of 2.80 ± 21.25 mm3 in the control group (p = 0.268). Conclusions: In ACS patients, serial autologous infusions of selective HDL delipidated plasma are clinically feasible and well tolerated. This therapy may offer a novel adjunct treatment for patients presenting with ACS. Further study will be needed to determine its ability to reduce clinical cardiovascular events. [Copyright &y& Elsevier]

Proton pump inhibitors are often prescribed for patients on clopidogrel to prevent gastrointestinal bleeding complications. Recent data suggest higher rates of adverse cardiovascular events in patients on proton pump inhibitors and clopidogrel, in comparison to patients on clopidogrel only. Both drugs are metabolized by similar pathways of the cytochrome P450 system, so proton pump inhibitors may inhibit the metabolism of clopidogrel to its active metabolite. This article reviews the pharmacodynamic and clinical evidence for this phenomenon. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve implantation (TAVI) without replacement requires precise knowledge of the anatomic dimensions and physical characteristics of the peripheral vasculature and aortic valve annulus at the insertion of the aortic valve leaflet and root at the level of the sinus of Valsalva. Multislice computed tomography (CT) allows detailed and precise assessment of the anatomic variables. Noncardiovascular structures are also amenable to assessment by CT. Of the 394 patients screened for TAVI, 259 (65.7%) had non-contrast CT to evaluate chest anatomy and contrast CT to evaluate ilio-femoral anatomy. Significant noncardiac findings were defined as those requiring immediate evaluation or intervention or additional clinical or radiologic follow-up. Noncardiovascular findings known before CT were not included. Of the 259 patients, 105 (40.5%) were men. The mean age was 82.3 ± 8.1 years. New, significant noncardiovascular findings were found in 89 (34.3%) and malignancy in 11 (4.2%) patients. Insignificant noncardiovascular findings were identified in 222 patients (85.7%). Signs of fluid retention were noted on CT in 105 patients (40.5%), with pleural effusion in 100 (38.6%), ascites in 17 (6.5%), and pericardial effusion in 14 (5.4%). Important peripheral vascular disease was found in 98 patients (37.8%), resulting in exclusion of 49 (19.1%) from TAVI using the transfemoral approach. An aortic aneurysm was found in 10 patients (3.8%) and a “porcelain” aorta (heavily calcified ascending aorta) in 19 (7.3%). In conclusion, malignancy and other noncardiovascular abnormalities are often found in patients who undergo CT for evaluation for TAVI. Populations must be meticulously examined to ensure that important findings are not missed. [Copyright &y& Elsevier]

Abstract: Currently percutaneous aortic valve replacement (PAVR) is indicated for patients at high surgical risk or for inoperable patients. Preprocedural evaluation is crucial to select the patients who will benefit the most and have the procedure done safely. This review will focus on risk assessment and the value of the available risk score systems, and on the screening process, which is the key for success in PAVR. Because of the large delivery system, careful evaluation of iliofemoral vessels is crucial. It is important to know the amount of atherosclerosis and plaque in the aortic arch and ascending aorta for potential risk for neurological events. Accurate measurement of aortic annulus diameter and coronary arteries origin before the procedure is important. Specific coexistent conditions can influence the procedure, such as left ventricular function or left ventricular hypertrophy with narrow outflow tract. Assessment of all these components is necessary for procedural planning of access approach, valve sizing, and deployment. [Copyright &y& Elsevier]

Background: Respiratory maneuvers can uncover manifestations of myocardial ischemia. Some pulse wave characteristics are strongly associated with significant coronary artery disease (S-CAD). An innovative test using the respiratory stress response (RSR) has been developed for the detection of S-CAD. It is based on spectral analysis of finger pulse wave oscillations measured by photoplethysmography during deep, paced breathing at a rate of six breaths per minute (0.1 Hz) over 70 s. Methods: RSR was assessed, prior to the procedure, in 150 consecutive patients referred for coronary angiography. It was calculated by analyzing the relative spectral power of the respiratory peak area at 0.1 Hz, using proprietary software. The coronary angiograms were analyzed by quantitative coronary angiography by 1 cardiologist who was blinded to the RSR results. S-CAD was defined as luminal stenosis >70% of > or = 1 coronary artery with a diameter > or = 2 mm, or left main stenosis >50%. A valid RSR was obtained in 150 of 153 patients (98%) with a mean age of 58.7 + or - 10.6 years (67% males). Results: S-CAD was found in 36 patients (24%). S-CAD patients had significantly lower RSR compared to patients without S-CAD (6.7% + or - 5.1 vs. 17.4% + or - 10.6; P<.001, respectively). Multivariate logistic regression analysis, adjusted for known CAD risk factors, showed that RSR is a strong independent indicator of S-CAD (odds ratio 41.2, 95% CI 12.2-139.3; P<.001). Conclusion: The innovative RSR test is a simple, noninvasive bedside or office-based tool for the detection of S-CAD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Injection of bone marrow cells (BMC) and endothelial progenitor cells (EPC) or application of stem-cell-mobilizing factors has been associated both with reduction or exacerbation of atherosclerosis and with unstable plaque phenotype. The discrepancies may reflect the cell type, dosing, duration, and route of administration of cells in these studies. The aim of this study was to determine the effects of peripheral-blood-derived endothelial progenitor cells (PBEPC) or unfractionated BMC obtained from inbred siblings on neointimal formation and inflammation in cholesterol-fed, balloon-denuded, and radiated rabbit iliac arteries. Methods: Rabbits were fed a 1.0% cholesterol diet for 14 days, followed by endothelial denudation in both iliac arteries, and continued on a 0.15% cholesterol diet. On day 42, denuded areas were radiated, and animals were randomized. The first group received PBEPC (n=5), the second group received BMC (n=4), and the third group received heparinized (20 IU) saline (Control; n=3). PBEPC were characterized by flow cytometry. Cells (5×106) or saline was administered twice through the ear vein: the first time at 1 h after radiation and the second time at 2 weeks after radiation. Four weeks after radiation, the animals were sacrificed, and arterial segments were processed for morphometry. Results: Administration of BMC or PBEPC from inbred siblings had no adverse effect. Lumen area (0.93±0.53 mm2), neointimal area (0.65±0.29 mm2), percent stenosis (44±21), and macrophage score (0.6±0.3) in controls were similar to those in cell-treated groups. Conclusion: This study demonstrates that, in the current animal model, either PBEPC or BMC failed to affect neointimal formation or inflammation. [Copyright &y& Elsevier]

The Xience V Everolimus-Eluting Coronary Stent System (Abbott Vascular, Santa Clara, California) drug-eluting stent (DES) is the most recent stent to undergo an extensive evaluation based on the initial requirements for DES approval. Safety and efficacy data were presented in a public meeting of the Food and Drug Administration (FDA) Circulatory System Devices Panel in November 2007. The sponsor presented data from their pre-clinical program demonstrating polymeric biocompatibility and a pharmacokenitic profile with complete drug elution by 4 months. Both the sponsor and FDA presented clinical efficacy and safety data from the SPIRIT trials. The EES demonstrated consistent late loss across the SPIRIT trials both in-stent and in-segment, including among subgroups of patients and lesions. Within this trial series, the primary endpoints were met in all studies with the establishment of superiority to both bare metal stents (BMS) and paclitaxel-eluting stents (PES) with respect to late loss and non-inferiority to PES with respect to target vessel failure through 9 months. The safety profile was reviewed by both presenters, demonstrating no evidence of an abnormal DES class-effect increase in stent thrombosis up to and between 1 and 2 years for the available data. The sponsor outlined an extensive integrated pre- and post-approval clinical program to further monitor potential safety concerns surrounding this class of stents. The Panel voted in favor of approval with conditions similar to those posed to the other DES; with FDA subsequently approving the stent for US commercial sale on July 2, 2008. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to determine how photodynamic therapy (PDT) promotes stabilization and reduction of regional atherosclerosis. Background: Photodynamic therapy, a combination of photosensitizer and targeted light to promote cell apoptosis, has been shown to reduce atherosclerotic plaque inflammation. Methods: Forty New Zealand White rabbits were fed with cholesterol. The iliac arteries were balloon denuded and randomized to receive either PhotoPoint PDT treatment (photosensitizer and light) (Miravant Medical Technologies, Santa Barbara, California), photosensitizer (MV0611) alone, or light alone and were then compared at 7 and 28 days. Arteries were examined for evidence of plaque volume, cell number, macrophage and smooth muscle cell (SMC) content, and plaque cell proliferation. Results: Compared with contralateral iliac artery controls at 7 days, plaque progression was reduced by approximately 35% (p < 0.01); plaque progression was further reduced to approximately 53% (p < 0.01) by 28 days, leading to an increase in lumen patency (p < 0.05). At 7 days after PDT, percent plaque area occupied by macrophages decreased by approximately 98% (p < 0.001) and SMCs by approximately 72% (p < 0.05). At 28 days after PDT, removal of macrophages was sustained (approximately 92% decrease, p < 0.001) and plaques were repopulated with non-proliferating SMCs (approximately 220% increase, p < 0.001). There was no evidence of negative or expansive arterial remodeling, thrombosis, or aneurysm formation. Conclusions: Photodynamic therapy simultaneously reduces plaque inflammation and promotes repopulation of plaques with a SMC-rich stable plaque cell phenotype while reducing disease progression. These early healing responses suggest that PDT is a promising therapy for the treatment of acute coronary syndromes. [Copyright &y& Elsevier]

Background: Platelet-derived peptide and nonpeptide growth factors are known to play pivotal roles in neointimal proliferation. Along with its antiplatelet activity of reducing P-selectin and hs-CRP, clopidogrel has also been shown to have anti-inflammatory properties. The aim of this study is to find out by modulating inflammation if clopidogrel can affect neointima formation in balloon-denuded iliac arteries of hypercholesterolemic rabbits. Methods and Results: Rabbits were fed with 1% cholesterol diet with (n = 20) or without (n = 20) clopidogrel (10 mg/kg body weight) for 7 days followed by balloon-denudation of endothelial layer in both the iliac arteries and continued on 0.15% cholesterol diet with or without clopidogrel. Four weeks later, the denuded area in both iliac arteries was radiated (n = 11, cholesterol-only group; n = 9, clopidogrel group) or sham treated (n = 10 from each group). Four weeks after radiation, animals were sacrificed and arterial segments were processed for morphometry. In the sham-treated clopidogrel group, neointimal area, percent stenosis, and macrophage score were 39% (P = 0.01), 32% (P = 0.02), and 50% (P = 0.02) smaller, respectively, when compared to the cholesterol-only group (0.48 ± 0.18, 32.42 ± 13.04, and 1.5 ± 0.83). There were no differences in the radiated group (0.89 ± 0.32, 50.34 ± 13.00, and 1.88 ± 1.27 vs. 0.93 ± 0.38, 59.41 ± 11.41, and 2.00 ± 0.74, respectively). Conclusion: This study demonstrates that clopidogrel reduces inflammation and neointimal formation in balloon-denuded iliac arteries of hypercholesterolemic rabbits. [ABSTRACT FROM AUTHOR]

Background: Biocorrodible iron stents carry the potential to overcome limitations, such as chronic inflammation and premature recoil, posed by biodegradable polymer and magnesium alloy stents. This study aimed to test the safety and efficacy of biocorrodible iron stents in porcine coronary arteries. Methods: Iron stents and cobalt chromium stents were randomly deployed in the coronary arteries of juvenile domestic pigs. Animals were sacrificed at 28 days, and the vessels were fixed and processed for histochemistry. Results: At 28 days, iron stents started to show signs of degradation without evidence of stent particle embolization or thrombosis without traces of excess inflammation, or fibrin deposition. At 28 days, the surface of the iron stent struts was black to brown and the vascular wall adjacent to the iron stent had a brownish tinge. There were no statistically significant differences in any of the measured parameters between segments implanted with iron and cobalt chromium stents. There were also no adverse effects in the persistent areas. Conclusion: The current study demonstrates that stents made of biocorrodible iron are safe. In some of the measured parameters, such as intimal thickness, intimal area, and percentage occlusion, there was a trend in favor of the iron stents. [ABSTRACT FROM AUTHOR]

Background: Absorbable metallic stents (AMS) utilizing Mg alloy carry advantages over permanent metallic stents because of their potential to eliminate stent thrombosis, chronic inflammation, or artifacts with noninvasive imaging. These stents, however, are associated with a modest degree of late recoil and intimal hyperplasia. The aim of the study was to test whether adjunct vascular brachytherapy (VBT) compared to AMS alone can overcome these limitations. Methods: Juvenile domestic pig coronary arteries underwent implantation of either AMS (n = 11) with prior adjunct VBT utilizing Sr/Y-90 β source seeds, with a dose of 24 Gy at 2 mm from the source, or AMS alone (n = 11). At 28 days following intravascular ultrasound, vessels were harvested and analyzed by histomorphometry. Results: Intravascular ultrasound analysis indicated that at follow-up, though statistically not significant, lumen and stent areas in the segments deployed with AMS following radiation were larger than those deployed with AMS alone (3.94 ± 1.38 and 3.53 ± 1.75 vs. 2.99 ± 1.05 and 3.58 ± 1.48). Extrastent plaque and intrastent plaque areas in the same segments were smaller (2.76 ± 0.82 and 0.24 ± 0.47 vs. 3.25 ± 1.94 and 0.58 ± 0.81). Morphometric data indicate that vessels in the VBT + AMS group showed characteristics of delayed healing and re-endothelialization. Neointimal area was significantly lower in the VBT + AMS group (0.49 ± 0.34) compared to AMS (1.3 ± 0.62, P = 0.001). Lumen area of the VBT + AMS was larger when compared with AMS alone (2.49 ± 0.82 vs. 1.75 ± 0.51, P = 0.02). Conclusion: VBT as an adjunct to AMS further reduces the intimal hyperplasia and improves the lumen area when compared to AMS alone but does not have any impact on late recoil. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We aimed to evaluate an effective dosage and safety profile of pimecrolimus as an anti-inflammatory drug for drug-eluting stents. Methods: In the dose finding study, coronary arteries of 20 domestic swine were randomly implanted with bare metal stents (ProKinetic and Guidant Vision), the ProKinetic stent with polylactic acid (PLLA), and pimecrolimus-eluting stents (32, 75, and 120 μg) over a period of 4 weeks. In addition, pimecrolimus (75 μg) and ProKinetic stents were randomly implanted into six swine over 3 months. In the safety study, the ProKinetic stent, the ProKinetic stent with PLLA, mid- (45 μg) and high-dose pimecrolimus (120 μg), and overlapping mid-dose stents were implanted over a period of 4 weeks. Mid-dose, ProKinetic stent, and ProKinetic stent with PLLA were implanted over a period of 3 months. Results: The dose finding study revealed excellent luminal patency with low percent occlusion (≈29% vs. ≈41%), injury (0.53–0.59 vs. 1.25), and inflammation (0.78–0.97 vs. 1.08) for the pimecrolimus group compared with the vision group. The safety study arm showed similar angiographic results for all tested groups, with a significantly larger minimal lumen diameter for pimecrolimus stents compared to PLLA stents. Except for the high-dose group and overlapping area of the overlapping group, promising morphometric results were found for pimecrolimus compared to bare metal stents. Conclusions: Present data suggest that pimecrolimus-eluting stents are safe and have a similar healing profile to bare metal stents. They may suppress inflammation, leading to a reduced intimal response and a milder inflammatory reaction in a porcine model. [Copyright &y& Elsevier]

Sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) significantly decrease the need for repeat interventions compared with bare metal stents. Comparative outcome data from randomized, controlled, head-to-head trials using these systems in a selected group of patients and lesions are conflicting; therefore, we compared clinical outcomes of unselected patients who underwent contemporary percutaneous coronary intervention with SES or PES implantation. In the REWARDS registry, 1-year clinical outcomes of 1,925 patients who received SESs were compared with 844 patients who received PESs. Outcomes at 30 days and 6 months were similar between groups, with a trend toward higher rates of stent thrombosis in the SES group compared with the PES group. Stent thrombosis rate at 12 months was significantly higher in the SES than in the PES group, with cumulative stent thrombosis rates of 1.9% in the SES group and 0.8% in the PES group (p = 0.034). However, overall rates of major adverse cardiac events (MACEs) were similar in the 2 groups at 12 months. After adjusting for significant multivariate predictors of MACEs, the hazard ratio at 1 year was 1.06 (95% confidence interval 0.85 to 1.33, p = 0.607) and the major predictors for MACEs were a history of renal failure, diabetes, previous myocardial infarction, cardiogenic shock, class III or IV heart failure, type C lesions, and saphenous vein grafts. In conclusion, use of SESs and PESs in unrestricted, contemporary practice had comparable outcomes in terms of low rates of revascularization and clinical events. Stent thrombosis continues to be a major concern for SESs and PESs. [Copyright &y& Elsevier]