A technology evaluation of the Onyx Frontier drug-eluting stent.

INTRODUCTION: Onyx FrontierTM represents the latest iteration within the family of zotarolimus-eluting stents (ZES), designed for the treatment of coronary artery disease. Approval by the Food and Drug Administration was granted in May 2022, and Conformité Européenne marking followed in August 2022. AREAS COVERED: We hereby review the principal design features of Onyx Frontier, highlighting differences and similarities with other currently available drug-eluting stents. In addition, we focus on the refinements of this newest platform as compared with previous ZES versions, including the attributes yielding its exceptional crossing profile and deliverability. The clinical implications related to both its newest and inherited characteristics will be discussed. EXPERT OPINION: The nuances of the latest Onyx Frontier, together with the continuous refinement previously witnessed throughout the development of ZES, lead to a latest generation device ideal for a diverse spectrum of clinical and anatomical scenarios. In particular, its peculiarities will be of benefit in the settings often offered by a progressively aging population, such as high bleeding risk patients and complex coronary lesions.

Safety and efficiency of percutaneous coronary intervention using a standardised optical coherence tomography workflow.

BACKGROUND: While intravascular imaging guidance during percutaneous coronary intervention (PCI) improves outcomes, routine intravascular imaging usage remains low, in part due to perceived inefficiency and safety concerns.  Aims: The LightLab (LL) Initiative was designed to evaluate whether implementing a standardised optical coherence tomography (OCT) workflow impacts PCI safety metrics and procedural efficiency. METHODS: In this multicentre, prospective, observational study, PCI procedural data were collected over 2 years from 45 physicians at 17 US centres. OCT-guided PCI incorporating the LL workflow (N=264), a structured algorithm using routine pre- and post-PCI OCT imaging, was compared with baseline angiography-only PCI (angio) (N=428). Propensity score analysis identified 207 matched procedures. Outcomes included procedure time, radiation exposure, contrast volume, device utilisation, and treatment strategy. RESULTS: Compared with angiography alone, LL workflow OCT-guided PCI increased the median procedural time by 9 minutes but reduced vessel preparation time (2 min LL workflow vs 3 min angio; p<0.001) and resulted in less unplanned additional treatment (4% LL workflow vs 10% angio; p=0.01). With LL workflow OCT guidance, fewer cineangiography views were needed compared to angiography guidance, leading to decreased radiation exposure (1,133 mGy LL workflow vs 1,269 mGy angio; p=0.02), with no difference in contrast utilisation between groups (p=0.28). Furthermore, LL workflow OCT guidance resulted in fewer predilatation balloons and stents being used, more direct stent placement, and greater stent post-dilatation than angiography-guided PCI. CONCLUSIONS: The incorporation of a standardised pre- and post-PCI OCT imaging workflow improves procedural efficiency and safety metrics, at a cost of a modestly longer procedure time.

Complementary Utility of Intravascular Lithotripsy With Atherectomy for Severely Calcified Coronary Stenoses in Contemporary Practice.

BACKGROUND: The effectiveness and safety of a contemporary combined approach that incorporates the novel intravascular lithotripsy (IVL) technology into conventional tools including atherectomy have yet to be studied. METHODS: We retrospectively included consecutive patients who underwent percutaneous coronary intervention (PCI) with IVL from March 2021 to February 2022. Effectiveness (residual stenosis of <30%) and safety outcomes (procedural complications and major adverse cardiovascular event [MACE] defined as a composite of all-cause death, myocardial infarction, or target vessel revascularization) were compared between patients undergoing IVL with and without atherectomy. RESULTS: A total of 109 patients underwent IVL, of whom 33 patients (30.3%) were treated with both IVL and atherectomy and had higher risk features including reduced cardiac function and more frequent use of mechanical circulatory support. Angiographic success for calcified de novo lesions was achieved in 85.7% and 90.6% of the combined and non-atherectomy groups, respectively (P=.49). Each group had one case of coronary perforation (P=.52) while major dissection occurred in 2 cases of calcific stent underexpansion in the combined group (6.1% vs 0%; P=.09). Thirty-day MACE occurred in 4.8% of patients including 3 deaths in the atherectomy group and 1 cardiac death and 1 myocardial infarction in the non-atherectomy group (P=.16). CONCLUSION: Procedural success and complications were similar in patients undergoing IVL with and without atherectomy when treating calcified de novo lesions. Those who required a combined approach represented a high-risk population with high mortality, suggesting that a multidisciplinary approach is needed to optimize case selection and care beyond PCI.

Residual SYNTAX II Score and long-term outcomes post-ST-elevation myocardial infarction in an urban US cohort: the Montefiore STEMI Registry.

BACKGROUND: Higher residual anatomic disease was associated with increased mortality in a recent randomized controlled trial of revascularization after ST-elevation myocardial infarction (STEMI). Less is known about the impact of residual disease post-STEMI in race-ethnic minorities. METHODS: Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX)- II (SS-II) score is an established scoring method for anatomic disease and prevalent co-morbidities to describe patient complexity. We evaluated residual (r) SS-II in 165 patients from a single center urban US registry (n = 1208) presenting for primary percutaneous coronary intervention of STEMI and treated for 3-vessel or left main and any combination of 0, 1, 2 or 3-vessel disease. RESULTS: The median age was 62 years (IQR 52-70), 29.1% women, 44.9% Hispanic/Latino and 19.4% non-Hispanic Black. Over median of 4.9 years (IQR 2.9-6.3), higher rSS-II was associated with increased death [hazard ratio 2.46 per SD increment in log rSS-II (~five-fold increment on the original scale) 95% CI 1.51, 3.99], death or all-cause readmission (hazard ratio 1.37 per SD increment in log rSS-II 95% CI, 1.11-1.70) and death or cardiovascular disease readmission (hazard ratio 1.46 per SD increment in log rSS-II 95% CI, 1.14-1.88). rSS-II was higher in older women with more co-morbidities, but not different by race-ethnicity. CONCLUSIONS: In summary, higher rSS-II was associated with long-term outcomes post-STEMI in a prospective urban, minority cohort, suggesting a potential role for risk stratification with this measure in a non-trial setting.

Very long-term clinical follow-up after fractional flow reserve-guided coronary revascularization.

BACKGROUND: Randomized trials using measurement of fractional flow reserve (FFR) to guide percutaneous coronary intervention (PCI) have demonstrated both safety and efficacy with regard to cardiac events. Real-world, long-term outcomes using an FFR-based revascularization strategy are unknown. METHODS: Prospective clinical data were collected on consecutive patients referred for coronary angiography and found to have lesions of intermediate severity where the operators were unable to make a decision regarding revascularization based on angiographic, clinical, and stress testing parameters. FFR was measured on intermediate lesions, and revascularization was deferred on those lesions with a measurement >0.8. Clinical outcomes of interest included death, myocardial infarction, and late revascularization status. RESULTS: A total of 151 patients were included in this study. Fifty-seven patients (37.7%) underwent revascularization based on their FFR measurement. The mean length of follow-up was 6.1 years (range, 5-10 years). Follow-up was completed in 97.0%. At the end of the follow-up period, 107 patients (70.9%) were alive. Late revascularization had been performed in 18 patients (11.9%). Comparing the initial revascularization group with the group in which revascularization was deferred, 64.9% and 74.5% were alive, respectively (P=.29). Of the initial revascularization group, 12.3% had undergone late revascularization of the lesion on which FFR was originally performed, compared with 11.7% in the deferred group (P=.99). CONCLUSIONS: FFR is a useful adjunct to coronary angiography in selecting patients with lesions of intermediate angiographic severity in whom coronary revascularization may be safely deferred.

Sonic hedgehog agonist fails to induce neural stem cell precursors in a porcine model of experimental intracranial hemorrhage.

BACKGROUND: The role of endogenous neural stem cell progenitors in recovery from intracranial hemorrhage remains to be elucidated. Proliferation of such stem cells in the subventricular zone has been described in rodent models of experimental intracranial hemorrhage. Administration of a sonic hedgehog agonist at the time of hemorrhage was hypothesized to increase the quantity of such precursor cells. METHODS: Two groups of pigs were subjected to injection of autologous blood into the right frontal lobe. One group was also injected at the same site with a sonic hedgehog agonist at the time of the hemorrhage to stimulate cell growth, and the other was given a vehicle control. The pigs received intravenous BrdU for 5 days postoperatively to label replicating cells, and then were sacrificed at intervals up to 21 days. RESULTS: Pigs in the hemorrhage only group demonstrated increased and more persistent BrdU staining in the subventricular zone relative to pigs in the group that received sonic hedgehog agonist. The latter group demonstrated increased BrdU activity in non-neural lineage cells in the area of the hemorrhage. CONCLUSION: Sonic hedgehog agonist did not induce subventricular zone neural stem cell progenitor division after experimental intracranial hemorrhage in a pig model.

Isolation, characterization, and differentiation of stem cells derived from the rat amniotic membrane.

Stem-cell-based therapies may offer treatments for a variety of intractable diseases. A fundamental goal in stem-cell biology concerns the characterization of diverse populations that exhibit different potentials, growth capabilities, and therapeutic utilities. We report the characterization of a stem-cell population isolated from tissue explants of rat amniotic membrane. Similar to mesenchymal stem cells, these amnion-derived stem cells (ADSCs) express the surface markers CD29 and CD90, but were negative for the lymphohematopoietic markers CD45 and CD11b. ADSCs exist in culture in a multidifferentiated state, expressing neuroectodermal (neurofilament-M), mesodermal (fibronectin), and endodermal (alpha-1-antitrypsin) genes. To assess plasticity, ADSCs were subjected to a number of culture conditions intended to encourage differentiation into neuroectodermal, mesodermal, and endodermal cell types. ADSCs cultured in a defined neural induction media assumed neuronal morphologies and up-regulated neural-specific genes. Under different conditions, ADSCs were capable of differentiating into presumptive bone and fat cells, indicated by the deposition of mineralized matrix and accumulated lipid droplets, respectively. Moreover, ADSCs cultured in media that promotes liver cell differentiation up-regulated liver-specific genes (albumin) and internalized low-density lipoprotein (LDL), consistent with a hepatocyte phenotype. To determine whether this observed plasticity reflects the presence of true stem cells within the population, we have derived individual clones from single cells. Clonal lines recapitulate the expression pattern of parental ADSC cultures and are multipotent. ADSCs have been cultured for 20 passages without losing their plasticity, suggesting long-term self-renewal. In sum, our data suggest that ADSCs and derived clonal lines are capable of long-term self-renewal and multidifferentiation, fulfilling all the criteria of a stem-cell population.