A Randomized Controlled Trial of Nonfasting vs Fasting Before Interventional Coronary Procedures: The TONIC Trial.

BACKGROUND: Fasting before coronary procedures is currently recommended to reduce complications despite the lack of scientific evidence. OBJECTIVES: The TONIC (Comparison Between Fasting and No Fasting Before Interventional Coronary Intervention on the Occurrence of Adverse Events) noninferiority trial investigated the safety and comfort of a nonfasting strategy (ad libitum food and drinks) vs traditional fasting (>6 hours for solid food and liquids) before coronary procedures. METHODS: In this monocentric, prospective, single-blind randomized controlled trial, 739 patients undergoing coronary procedures were included and randomized to a fasting or a nonfasting strategy. Emergency procedures were excluded. The primary endpoint was a composite of vasovagal reaction, hypoglycemia (defined by blood sugar ≤0.7 g/L), and isolated nausea and/or vomiting. Noninferiority margin was 4%. Secondary endpoints were contrast-induced nephropathy and patients' satisfaction. RESULTS: Among the 739 procedures (697 elective and 42 semiurgent), 517 angiographies, and 222 angioplasties (including complex and high-risk procedures) were performed. The primary endpoint occurred in 30 of 365 nonfasting patients (8.2%) vs 37 of 374 fasting patients (9.9%), demonstrating noninferiority (absolute between-group difference, -1.7%; 1-sided 95% CI upper limit: 1.8%). No food-related adverse event occurred, and contrast-related acute kidney injuries were similar between groups. Overall, procedure satisfaction and perceived pain were similar in both groups, but nonfasting patients reported less hunger and thirst (P < 0.01). In case of redo coronary procedures, most patients (79%) would choose a nonfasting strategy. CONCLUSIONS: The TONIC randomized trial demonstrates the noninferiority of a nonfasting strategy to the usual fasting strategy for coronary procedures regarding safety, while improving patients' comfort.

Procedural embolic protection strategies for carotid artery stenting: current status and future prospects.

INTRODUCTION: Carotid artery angioplasty and stenting (CAS) is an established procedure to treat carotid artery stenosis for either primary or secondary prevention of stroke. Randomized clinical trials have shown an increased risk of periprocedural cerebrovascular events with CAS compared with carotid endarterectomy (CEA). Several strategies have been proposed to mitigate this risk, including alternative vascular access site, proximal/distal embolic protection devices, and dual-layer stents, among others. AREAS COVERED: This review provides a general overview of current embolic protection strategies for CAS. The phases of the procedure which can affect the early risk of stroke and how to reduce it with novel techniques and devices have been discussed. EXPERT OPINION: Innovations in device technologies have dramatically improved the safety and efficacy of CAS. To minimize the gap with surgery, a thorough, patient-oriented approach should be pursued. Endovascular technologies and techniques should be selected on an individual basis to address unique lesion characteristics and vascular anatomies. Meticulous pre-procedural planning, both clinical and anatomical, is needed to assess the embolic risk of each procedure. Only by having an in-depth understanding of the wide range of available endovascular devices and techniques, the operator will choose the most appropriate strategy to optimize CAS results.

On-line estimated peak skin dose during percutaneous coronary intervention for chronic total occlusion using new patient dose mapping technology.

BACKGROUND: X-ray exposure during complex percutaneous coronary intervention is a very important issue. AIM: To reduce patient peak skin dose during percutaneous coronary intervention procedures for chronic total occlusion using on-line estimated peak skin dose software (Dose Map). METHODS: Throughout the procedure, Dose Map provided a map of local cumulative peak skin dose. This map was displayed in-room from 1Gy cumulative air kerma, and was updated every 0.5Gy. The operator's actions to minimize deterministic risks following map notification were collected. Skin reaction was evaluated 3 months after the procedure. A comparison with our historical X-ray exposure data (207 patients from January 2013 to July 2014) was performed. RESULTS: From November 2015 to October 2016, 97 patients (Japanese chronic total occlusion score 2.1±1.1; 100 percutaneous coronary intervention procedures for chronic total occlusion) were prospectively enrolled. Fluoroscopy time was 40.8 (21.6-60.3) minutes, cumulative air kerma 1884 (1144-3231) mGy, estimated peak skin dose 962 (604-1474) mGy and kerma area product 115.8 (71.5-206.7) Gy.cm2. Cumulative air kerma was>3Gy in 28% of cases, and>5Gy in 11% of cases. In 68% of cases, at least one action was taken by the operator after map notification to optimize skin dose distribution. Main changes included: gantry angulation (52%); field of view (25%); and collimation (13%). No skin injuries were observed at follow-up. In comparison with our chronic total occlusion historical radiation data, median cumulative air kerma and kerma area product were reduced by 31% and 33%, respectively (P<0.005. CONCLUSION: Online skin dose mapping software allows the distribution of patient skin dose during complex percutaneous coronary intervention procedures, and may minimize X-ray exposure.

Percutaneous angio-guided versus surgical veno-arterial ECLS implantation in patients with cardiogenic shock or cardiac arrest.

BACKGROUND: Veno-arterial Extracorporeal Life Support (V-A ECLS) has gained increasing place into the management of patients with refractory cardiogenic shock or cardiac arrest. Both surgical and percutaneous approach can be used for cannulation, but percutaneous approach has been associated with fewer complications. Angio-guided percutaneous cannulation and decannulation may further decrease the rate of complication. We aimed to compare outcome and complication rates in patients supported with V-A ECLS through percutaneous angio-guided versus surgical approach. METHODS: We included all patients with emergent peripheral femoro-femoral V-A ECLS implantation for refractory cardiogenic shock or cardiac arrest in our center from March 2018 to March 2021. Survival and major complications (major bleeding, limb ischemia and groin infection) rates were compared between the percutaneous angio-guided and the surgical groups. RESULTS: One hundred twenty patients received V-A ECLS, 59 through surgical approach and 61 through angio-guided percutaneous approach. Patients' baseline characteristics and severity scores were equally balanced between the 2 groups. Thirty-day mortality was not significantly different between the 2 approaches. However, angio-guided percutaneous cannulation was associated with fewer major vascular complications (42% vs. 11%, p > 0.0001) and a higher rate of V-A ECLS decannulation. In multivariate analysis, percutaneous angio-guided implantation of V-A ECLS was independently associated with a lower probability of major complications. CONCLUSION: Compared to surgical approach, angio-guided percutaneous V-A ECLS implantation is associated with fewer major vascular complications. Larger studies are needed to confirm those results and address their impact on mortality.

Complete percutaneous angio-guided approach using preclosing for venoarterial extracorporeal membrane oxygenation implantation and explantation in patients with refractory cardiogenic shock or cardiac arrest.

BACKGROUND: The approach for veno-arterial extracorporeal membrane oxygenation implantation (VA-ECMO) in patients with cardiogenic shock can be either surgical or percutaneous. Complete angio-guided percutaneous implantation and explantation could decrease vascular complications. We sought to describe the initial results of complete percutaneous angio-guided ECMO implantation and explantation using preclosing. METHODS: All consecutive patients who underwent peripheral femoro-femoral VA-ECMO percutaneous implantation for refractory cardiogenic shock or cardiac arrest were enrolled in a prospective registry (03/2018-12/2020). Percutaneous preclosing using two closing devices (Perclose ProGlide, Abbott) inserted before cannulation was used in both femoral artery and vein. Explantation was performed using a crossover technique under angiographic guidance. The occurrence of vascular complication was recorded. RESULTS: Among the 56 patients who underwent percutaneous VA-ECMO implantation for cardiogenic shock or refractory cardiac arrest, 41 underwent preclosing. Femoral vessel cannulation was successful in all patients and total cannulation time was 20 (10-40) min. Weaning from ECMO was possible in 22/41 patients (54%) and 12 (29%) patients were alive at day 30. Significant vascular complications occurred in 2/41 patients. Percutaneous decannulation was performed in 20 patients with 19/20 technical success rate. All femoral arteries and veins were properly closed using the pre-closing devices without bleeding on the angiographic control except for one patient in whom surgical closure of the artery was required. No patient required transfusion for access related significant bleeding and no other vascular complication occurred. Furthermore, no groin infection was observed after full percutaneous implantation and removal of ECMO. CONCLUSION: Emergent complete percutaneous angio-guided VA-ECMO implantation and explantation using pre-closing technique can be an attractive strategy in patients referred for refractory cardiogenic shock.

Feasibility of Prone Position Coronary Angiography in a Patient With COVID-19 Pneumonia and Refractory Hypoxemia.

A 57-year-old woman hospitalized for a COVID-19 (coronavirus disease-2019)-related refractory acute respiratory distress syndrome developed a few days later anteroseptal ST-segment elevation with acute systolic dysfunction. Coronary angiography was performed with the patient in prone (face down) position, owing to the necessity to maintain a reasonable oxygen saturation during the examination. (Level of Difficulty: Intermediate.).

New-generation drug-eluting stents for left main coronary artery disease according to the EXCEL trial enrollment criteria: Insights from the all-comers, international, multicenter DELTA-2 registry.

BACKGROUND: Percutaneous coronary intervention (PCI) has been established as an alternative treatment option to coronary artery by-pass graft (CABG) surgery in patients with left main coronary artery disease (LMCAD). Whether the findings of randomized controlled trials are applicable to a real-world patient population is unclear. METHODS: We compared the outcomes of PCI with new-generation DES in the all-comer, international, multicenter DELTA-2 registry retrospectively evaluating mid-term clinical outcomes with the historical CABG cohort enrolled in the DELTA-1 registry according to the EXCEL key inclusion or exclusion criteria. The primary endpoint was the composite of death, myocardial infarction, or stroke at the median time of follow-up time of 501 days. The consistency of the effect of DELTA-2 PCI versus DELTA-1 CABG according to the EXCEL enrollment criteria was tested using propensity score-adjusted Cox regression models. RESULTS: Out of 3986 patients enrolled in the DELTA-2 PCI registry, 2418 were EXCEL candidates and 1568 were not EXCEL candidates. The occurrence of the primary endpoint was higher among non-EXCEL candidates compared with EXCEL candidates (15.4% vs. 6.9%; hazard ratio 2.52; 95% confidence interval 2.00-3.16; p < 0.001). Among 901 patients enrolled in the historical DELTA-1 CABG cohort, 471 were EXCEL candidates and 430 were not EXCEL candidates. When comparing the DELTA-2 PCI with the DELTA-1 CABG cohort, the occurrence of the primary endpoint was lower in the PCI group compared with the historical CABG cohort among EXCEL candidates (6.9% vs. 10.7%; adjusted hazard ratio: 0.65; 95% confidence interval: 0.45-0.92), while no significant difference was observed among non-EXCEL candidates (15.4% vs. 12.5%; adjusted hazard ratio: 0.94; 95% confidence interval: 0.67-1.33) with evidence of statistical interaction (adjusted interaction p-value = 0.002). CONCLUSIONS: In a real-world population, PCI can be selected more favorably as an alternative to CABG in patients fulfilling the enrollment criteria of the EXCEL trial.

Fluoroscopic Anatomy of Right-Sided Heart Structures for Transcatheter Interventions.

Performing transcatheter tricuspid valve interventions requires a thorough knowledge of right-heart imaging. Integration of chamber views across the spectrum of imaging modalities (i.e., multislice computed tomography, fluoroscopy, and echocardiography) can facilitate transcatheter interventions on the right heart. Optimal fluoroscopic viewing angles for guiding interventional procedures can be obtained using pre-procedural multislice computed tomography scans. The present paper describes fluoroscopic viewing angles necessary to appreciate right-heart chamber anatomy and their relationship to echocardiography using multislice computed tomography.

Effects of statins on plaque rupture assessed by optical coherence tomography in patients presenting with acute coronary syndromes: insights from the optical coherence tomography (OCT)-FORMIDABLE registry.

Aims: Chronic pre-treatment with statins may reduce mortality and morbidity in patients experiencing acute coronary syndromes (ACS), but mechanisms accounting for these findings are not completely understood. Methods and results: The optical coherence tomography (OCT)-Formidable registry retrospectively enrolled 285 consecutive patients with ACS undergoing OCT in 9 European centres. Mean age was 60.4 ± 12.8 years, 148 (51.9%) patients had hyperlipemia, 45 (15.8%) diabetes mellitus and 142 (49.8%) presented with ST Segment Elevation Myocardial Infarction (STEMI). Patients were stratified according to statin prescription: 150 (52.6%) were on chronic pre-treatment with statins before ACS and were more likely to present with non-ST segment elevation acute coronary syndromes (NSTE-ACS) at admission (111, 74%) rather than STEMI, while the opposite was observed for patients not on statins. The primary end-point of ruptured plaque at OCT occurred significantly less frequently in the patients on chronic pre-treatment with statins [odds ratio (OR) 0.375, 95% confidence interval (CI) 0.185-0.759, P = 0.006]. The secondary end-point of thin-cap fibro-atheroma (TCFA) at any site was significantly less frequent in the statin group (OR 0.423, 95%CI 0.213-0.840, P = 0.014). No differences were observed for the secondary end-point of not-ruptured TCFA as the culprit lesion. Pre-specified sensitivity analysis was conducted according to the pattern of ACS: the reported differences were confirmed for NSTE-ACS patients, with a trend towards less plaque rupture and a significant reduction of TCFA at any site with statins, but not for STEMI. Conclusions: Chronic pre-treatment with statins is associated with a reduced prevalence of ruptured plaques in patients presenting with ACS, particularly in those with NSTE-ACS. Statins bear hence the potential to reduce morbidity during the acute phase of ACS.

The DELTA 2 Registry: A Multicenter Registry Evaluating Percutaneous Coronary Intervention With New-Generation Drug-Eluting Stents in Patients With Obstructive Left Main Coronary Artery Disease.

OBJECTIVES: The aim of this study was to evaluate clinical outcomes of unprotected left main coronary artery percutaneous coronary intervention (PCI) with new-generation drug-eluting stents in a "real world" population. BACKGROUND: PCI of the unprotected left main coronary artery is currently recommended as an alternative to coronary artery bypass grafting (CABG) in selected patients. METHODS: All consecutive patients with unprotected left main coronary artery stenosis treated by PCI with second-generation drug-eluting stents were analyzed in this international, all-comers, multicenter registry. The results were compared with those from the historical DELTA 1 (Drug Eluting Stent for Left Main Coronary Artery) CABG cohort using propensity score stratification. The primary endpoint was the composite of death, myocardial infarction (MI), or stroke at the median time of follow-up. RESULTS: A total of 3,986 patients were included. The mean age was 69.6 ± 10.9 years, diabetes was present in 30.8%, and 21% of the patients presented with acute MI. The distal left main coronary artery was involved in 84.6% of the lesions. At a median of 501 days (≈17 months) of follow-up, the occurrence of the primary endpoint of death, MI, or cerebrovascular accident was lower in the PCI DELTA 2 group compared with the historical DELTA 1 CABG cohort (10.3% vs. 11.6%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.55 to 0.98; p = 0.03). Of note, an advantage of PCI was observed with respect to cerebrovascular accident (0.8% vs. 2.0%; adjusted hazard ratio: 0.37; 95% confidence interval: 0.16 to 0.86; p = 0.02), while an advantage of CABG was observed with respect to target vessel revascularization (14.2% vs. 2.9%; adjusted hazard ratio: 3.32; 95% confidence interval: 2.12 to 5.18; p < 0.0001). CONCLUSIONS: After a median follow-up period of 17 months, PCI with new-generation drug-eluting stents was associated with an overall low rate of the composite endpoint of death, MI, or cerebrovascular accident.

Reproducibility of serial optical coherence tomography measurements for lumen area and plaque components in humans (The CLI-VAR [Centro per la Lotta Contro l'Infarto-variability] II study).

Frequency-domain optical coherence tomography (FD-OCT) is a promising intracoronary imaging technique to study atherosclerosis. Indeed, its unprecedented spatial resolution allows the assessment of fibrous cap thickness, lipid pool and features of plaque vulnerability. Aim of this study was to determine the reproducibility of the in vivo FD-OCT measurements of lumen area and plaque components in serial studies. Twenty-six patients undergoing FD-OCT assessment of intermediate lesion during coronary angiography were included in this study. FD-OCT pullbacks were acquired twice from the same coronary segment at interval of 5 min without additional intervention and analyzed off-line at an independent imaging core laboratory. Lumen diameter (LD), lumen area (LA), fibrous cap (FC) thickness and lipid pool (LP) arc extension measurements were compared in 440 matched frames. Both the per-segment and per-frame analyses showed excellent correlation coefficients for the inter-pullback comparisons for all parameters explored (R > 0.95 and p < 0.001 in all cases). Accordingly, the Bland-Altman estimates of bias showed non-significant differences in the inter-pullback comparisons at all levels. Per-frame analysis showed a slightly variations of LA in 45.8% of cases with changes greater than 2% likely related to different phases of cardiac cycle. Nevertheless, nor FC thickness or circumferential arc of LP were affected by LA changes during serial FD-OCT acquisition. This study showed an excellent reproducibility of lumen and plaque component measurements obtained with FD-OCT in vivo. Thus, this intracoronary imaging technique could be used to assess atherosclerosis progression and describe accurate plaque evolution in repeated serial studies.

Managing bioabsorbable vascular scaffold failure: combined scaffold restenosis and late-acquired coronary aneurysm treated with self-expandable stent.

A 50-year-old man underwent coronary angiography for stable angina with evidence of chronic total occlusion of the right coronary artery. Chronic total occlusion recanalization was performed with implantation of 4 overlapping bioresorbable vascular scaffolds. At 12 months, elective follow-up coronary angiography documented an asymptomatic 90% in-scaffold restenosis of the right coronary artery located in the mid portion of a newly late-acquired aneurysm. To address the challenging issue introduced by the varying reference vessel diameters, a self-expandable stent was implanted.

Comparative one-year effectiveness of percutaneous coronary intervention versus coronary artery bypass grafting in patients <75 versus ≥75 years with unprotected left main disease (from the CUSTOMIZE Registry).

There is a lack of knowledge on the interaction between age and left main coronary artery revascularization. The aim of this study was to investigate the comparative effectiveness of percutaneous coronary intervention (PCI) with drug-eluting stents and coronary artery bypass grafting (CABG) in patients with left main coronary artery disease aged <75 versus ≥75 years. Of a total of 894 patients included, 692 (77.4%) were aged <75 years and 202 (23.6%) ≥75 years. PCI was found to be significantly different from CABG with respect to the composite of major adverse cardiac events at 1-year follow-up in patients aged <75 years (15.5% vs 8.5%, p = 0.01) but not in those aged ≥75 years (16.4% vs 13.9%, p = 0.65). This finding was consistent after statistical adjustment for baseline confounders in the 2 groups (adjusted hazard ratio [AHR] 2.2, 95% confidence interval 1.2 to 4.1, p = 0.016 in younger patients; AHR 0.9, 95% confidence interval 0.3 to 3.0, p = 0.88 in older patients). In the 2 groups, PCI and CABG showed similar adjusted risks for all-cause death, cardiac death, and myocardial infarction. Target lesion revascularization occurred more frequently in patients aged <75 years treated with PCI compared to CABG (AHR 5.1, 95% confidence interval 1.9 to 13.6, p = 0.001) but not in those aged ≥75 years. A significant interaction between age and treatment with regard to major adverse cardiac events was identified (adjusted p for interaction = 0.034). In conclusion, compared to younger patients, elderly patients with left main disease are likely to derive the maximal gain from a less invasive procedure such as PCI.

Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is associated with increased liver-related mortality. Disturbances in hepatic lipid homeostasis trigger oxidative stress and inflammation (ie, lipotoxicity), leading to the progression of NASH. This study aimed at identifying whether silibinin may influence the molecular events of lipotoxicity in a mouse model of NASH. Eight-week-old db/db mice were fed a methionine-choline deficient (MCD) diet for 4 weeks and treated daily with silibinin (20 mg/kg intraperitoneally) or vehicle. Liver expression and enzyme activity of stearoyl-CoA desaturase-1 and acyl-CoA oxidase, and expression of liver fatty acid-binding protein were assessed. Hepatic levels of reactive oxygen species, thiobarbituric acid-reactive substances (TBARS), 3-nitrotyrosine (3-NT), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NFkB) activities were also determined. Silibinin administration decreased serum alanine aminotransferase and improved liver steatosis, hepatocyte ballooning, and lobular inflammation in db/db mice fed an MCD diet. Gene expression and activity of stearoyl-CoA desaturase-1 were reduced in db/db mice fed an MCD diet compared with lean controls and were increased by silibinin; moreover, silibinin treatment induced the expression and activity of acyl-CoA oxidase and the expression of liver fatty acid-binding protein. Vehicle-treated animals displayed increased hepatic levels of reactive oxygen species and TBARS, 3-NT staining, and iNOS expression; silibinin treatment markedly decreased reactive oxygen species and TBARS and restored 3-NT and iNOS to the levels of control mice. db/db mice fed an MCD diet consistently had increased NFkB p65 and p50 binding activity; silibinin administration significantly decreased the activity of both subunits. Silibinin treatment counteracts the progression of liver injury by modulating lipid homeostasis and suppressing oxidative stress-mediated lipotoxicity and NFkB activation in experimental NASH.

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic fatty liver disease is a chronic metabolic disorder with significant impact on cardiovascular and liver mortality. AIMS: In this study, we examined the effects of silibinin on liver and myocardium injury in an experimental model of nonalcoholic fatty liver disease. METHODS: A four-week daily dose of silibinin (20 mg/kg i.p.) was administrated to db/db mice fed a methionine-choline deficient diet. Hepatic and myocardial histology, oxidative stress and inflammatory cytokines were evaluated. RESULTS: Silibinin administration decreased HOMA-IR, serum ALT and markedly improved hepatic and myocardial damage. Silibinin reduced isoprostanes, 8-deoxyguanosine and nitrites/nitrates in the liver and in the heart of db/db fed the methionine-choline deficient diet, whereas glutathione levels were restored to lean mice levels in both tissues. Consistently, liver mitochondrial respiratory chain activity was significantly impaired in untreated mice and was completely restored in silibinin-treated animals. TNF-α was increased whereas IL-6 was decreased both in the liver and heart of db/db fed methionine-choline deficient diet. Silibinin reversed heart TNF-α and IL-6 expression to control mice levels. Indeed, liver JNK phosphorylation was reduced to control levels in treated animals. CONCLUSIONS: This study demonstrates a combined effectiveness of silibinin on improving liver and myocardial injury in experimental nonalcoholic fatty liver disease.

Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice.

BACKGROUND: Cardiovascular diseases (CVD) in diabetic patients have endothelial dysfunction as a key pathogenetic event. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), plays a pivotal role in endothelial dysfunction. Different natural polyphenols have been shown to preserve endothelial function and prevent CVD. In this study, we assessed the effect of silibinin, a widely used flavonolignan from milk thistle, on ADMA levels and endothelial dysfunction in db/db mice. METHODS: Eight-week-old db/db mice were administrated a 20 mg/Kg i.p. daily dose of silibinin (n = 6) or vehicle (n = 6) for four weeks. Heterozygous lean db/m mice served as control. Plasma, aorta and liver ADMA levels were determined by ELISA. Vascular reactivity to phenilephrine (PE), acetylcholine (ACh), sodium nitroprusside (SNP) and ADMA was assessed in isolated aortic segments, in wire myograph. RESULTS: Plasma and aorta ADMA levels were higher in db/db than in control lean mice. Silibinin administration markedly decreased plasma ADMA; consistently, aorta ADMA was reduced in silibinin-treated animals. Plasma and aorta ADMA levels exhibited a positive correlation, whereas liver ADMA was inversely correlated with both plasma and aorta ADMA concentrations. Endothelium-(NO)-dependent vasodilatation to ACh was impaired in db/db mice and was restored in the silibinin group, in accordance with the observed reduction of plasma and vascular levels of ADMA. Endothelium-independent vasodilatation to SNP was not modified by silibinin administration; contractile tone induced in isolated aorta from db/db mice by challenging with exogenous ADMA was not affected by the treatment. CONCLUSIONS: Silibinin markedly improves endothelial dysfunction in db/db mice by reducing circulating and vascular ADMA levels. Clinical studies are warranted to assess the efficacy of silibinin for cardiovascular protection.