Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI.

BACKGROUND: Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN: The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 14 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the noninferiority between stents with respect to a device-oriented composite end point of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY: The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI.

Renal insufficiency following contrast media administration trial III: Urine flow rate-guided versus left-ventricular end-diastolic pressure-guided hydration in high-risk patients for contrast-induced acute kidney injury. Rationale and design.

BACKGROUND: Urine flow rate (UFR)-guided and left-ventricular end-diastolic pressure (LVEDP)-guided hydration regimens have been proposed to prevent contrast-induced acute kidney injury (CIAKI). The REnal Insufficiency Following Contrast MEDIA Administration triaL III (REMEDIAL III) is a randomized, multicenter, investigator-sponsored trial aiming to compare these two hydration strategies. METHODS: Patients at high risk for CIAKI (that is, those with estimated glomerular filtration rate ≤ 45 mL/min/1.73 m2 and/or with Mehran's score ≥11 and/or Gurm's score >7) will be enrolled. Patients will be randomly assigned to (a) LVEDP-guided hydration with normal saline (LVEDP-guided group) and (b) UFR-guided hydration carried out by the RenalGuard system (RenalGuard group). Seven-hundred patients (350 in each arm) will be enrolled. In the LVEDP-guided group the fluid infusion rate will be adjusted according to the LVEDP as follows: 5 mL kg-1 hr-1 for LVEDP ≤12 mmHg, 3 mL kg-1 hr-1 for LVEDP 13-18 mmHg, and 1.5 mL kg-1 hr-1 for LVEDP >18 mmHg. In the RenalGuard group hydration with normal saline plus low-dose of furosemide is controlled by the RenalGuard system, in order to reach and maintain a high (>300 mL/hr) UFR. In all cases, iobitridol (a low-osmolar, nonionic contrast agent) will be administered. RESULTS: The primary endpoint is the composite of CIAKI (i.e., serum creatinine increase ≥25% and/or ≥0.5 mg/dL from the baseline to 48 hr after contrast media exposure) and/or acute pulmonary edema. CONCLUSION: The REMEDIAL III will test the hypothesis that the UFR-guided hydration is superior to the LVEDP-guided hydration to prevent the composite of CIAKI and/or acute pulmonary edema.

Persistent serum creatinine increase following contrast-induced acute kidney injury.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) may led to both a transient and a persistent serum creatinine (sCr) increase. OBJECTIVES: To assess whether serum cystatin C (sCyC) and urine and serum neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) are useful in the early identification of persistent sCr increase following CI-AKI. METHODS: One hundred and eighteen patients who developed CI-AKI were included into the study. Persistent sCr elevation was defined as a persistent increase ≥0.3 mg dL-1 at 1 month after contrast media (CM) administration. RESULTS: sCr levels recovered in 87 patients (74%; Transient group), whereas a persistent elevation of sCr was observed in the remaining 31 patients (26%; Persistent group). By multivariable logistic regression analysis, independent predictors of persistent sCr increase were insulin therapy, uNGAL at 48 hr and absolute sCr difference between 48 and 72 hr. On the contrary, sCyC assessment did not help in the early identification of this subset of patients. By receiver operating curve analysis, the best cutoff values for predicting persistent sCr increase were uNGAL ≥0.50 ng dL-1 at 48 hr, and the absolute sCr increase ≥0.20 mg dL-1 between 48 and 72 hr. CONCLUSIONS: uNGAL ≥0.50 ng dL-1 at 48 hr and absolute sCr increase ≥0.20 mg dL-1 between 48 and 72 hr but not sCyC are useful in the early identification of patients developing persistent sCr increase after CM administration.

What We Learned with Recent Network Meta-analyses on Atherosclerosis Prevention and Treatment.

PURPOSE OF REVIEW: The management of atherosclerosis requires a complex integration of the knowledge on its pathophysiology, patient values, and the synthesis of the global scientific evidence informing on its prevention and treatment. Novel statistical methods such as umbrella reviews and network meta-analyses (NMAs) offer a unique opportunity for integrating different sources of evidence stemming from randomized controlled trials (RCTs) or internally valid observational studies. We aimed to provide an updated perspective on the most important contributions of recent network meta-analyses on atherosclerosis prevention and treatment. RECENT FINDINGS: We identified and appraised in detail 9 NMAs on atherosclerosis prevention, all published in 2016, whereas a total of 12 NMAs on atherosclerosis treatment published between 2014 and 2016 were identified. Most NMAs focused on RCTs only, with primary prevention analyses including on average more trials and patients than those focusing on secondary prevention. In most cases, conclusive findings for clinically relevant outcomes could be provided. Yet, several inconclusive findings were reported, suggesting thus that NMAs can also guide new research by emphasizing where new evidence is most needed. NMAs provide a unique opportunity for poignant synthesis of high-quality evidence. In particular, they seem particularly promising when the evidence base has reached a sufficient level of maturity, and several competing interventions require comprehensive and comparative risk-benefit appraisal.

CT Coronary Angiography: Technical Approach and Atherosclerotic Plaque Characterization.

Coronary computed tomography angiography (CCTA) currently represents a robust imaging technique for the detection, quantification and characterization of coronary atherosclerosis. However, CCTA remains a challenging task requiring both high spatial and temporal resolution to provide motion-free images of the coronary arteries. Several CCTA features, such as low attenuation, positive remodeling, spotty calcification, napkin-ring and high pericoronary fat attenuation index have been proved as associated to high-risk plaques. This review aims to explore the role of CCTA in the characterization of high-risk atherosclerotic plaque and the recent advancements in CCTA technologies with a focus on radiomics plaque analysis.

Dual-Energy CT of the Heart: A Review.

Dual-energy computed tomography (DECT) represents an emerging imaging technique which consists of the acquisition of two separate datasets utilizing two different X-ray spectra energies. Several cardiac DECT applications have been assessed, such as virtual monoenergetic images, virtual non-contrast reconstructions, and iodine myocardial perfusion maps, which are demonstrated to improve diagnostic accuracy and image quality while reducing both radiation and contrast media administration. This review will summarize the technical basis of DECT and review the principal cardiac applications currently adopted in clinical practice, exploring possible future applications.

Clinical Outcome of Edoxaban vs. Vitamin K Antagonists in Patients with Atrial Fibrillation and Diabetes Mellitus: Results from a Multicenter, Propensity-Matched, Real-World Cohort Study.

Diabetes mellitus (DM) is a chronic metabolic disease which is independently associated with unfavorable clinical outcomes in patients with atrial fibrillation (AF). Few real-world data are available about the clinical performance of non-vitamin K oral anticoagulants (NOACs) among patients with atrial fibrillation and diabetes. The aim of our propensity score-matched cohort study was to compare the safety and effectiveness of Edoxaban versus well-controlled vitamin K antagonists (VKAs) therapy among this population. In this study, we considered patients with AF and diabetes on Edoxaban or VKAs therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MB) and thromboembolic events (a composite of ischemic stroke, transient ischemic attack, systemic embolism) was respectively considered primary safety and effectiveness outcome. We identified 557 AF patients with diabetes who received Edoxaban (n: 230) or VKAs (n: 327) treatment. After propensity score matching analysis, 135 Edoxaban and 135 VKA recipients with similar clinical characteristics were evaluated. The mean follow-up was 27 ± 3 months. The incidence rate of thromboembolic events (TE) was 3.0 per 100 person-years (1.11 in Edoxaban vs. 1.9 in the VKA group, hazard ratio (HR): 0.59; 95% confidence interval (CI), 0.14 to 2.52; p = 0.48). The incidence rate of major bleedings (MB) was 3.7 per 100 person-years (1.2 in Edoxaban vs. 2.7 in the VKA group, HR: 0.43; 95% CI, 0.10 to 1.40; p = 0.14). The incidence rate of intracranial hemorrhage was 0.35 per 100 person-years in Edoxaban vs. 0.74 in the VKA group (HR: 0.49; 95% CI: 0.05 to 5.54; p = 0.56). A positive net clinical benefit (NCB) of Edoxaban over VKAs was found (+1.39). Insulin therapy (HR: 1.76, p = 0.004) and glycated hemoglobin (HR: 1.17, p = 0.002) were found to be independent predictors of TE; moreover, the concomitant use of antiplatelet drugs (HR: 2.41, p = 0.001) was an independent predictor of MB. Conclusions: Our data support the hypothesis of the safety and efficacy of Edoxaban for use in patients with AF and diabetes, justified by a favorable NCB over VKAs.

Left ventricular support during complex transradial percutaneous coronary intervention for complete revascularization.

Although there is not uniform definition of high-risk percutaneous coronary intervention (PCI), patients with severe three-vessel disease, left main disease, single remaining patent vessel and/or depressed left ventricular ejection fraction are considered a high-risk population. In this setting, periprocedural hemodynamic instability represents a serious issue. Percutaneous mechanical circulatory support (MCS) devices may improve both safety and efficacy of high-risk PCI. Indeed, MCS help to maintain coronary perfusion pressure and reduce myocardial workload, providing the operator sufficient time to reach the target of complete revascularization. The most used MCS are intra-aortic balloon pump and Impella. There are a plenty of data in literature about the efficacy and safety of the use of MCS in high-risk PCI performed through the femoral access. However, there is a paucity of data about the use of MCS in transradial high-risk PCI. Radial over femoral access has been showed to reduce bleeding complications and therefore may further improve the outcome of high-risk PCI. Herein we report a case of transradial high-risk PCI supported by the Impella 2.5 L and review the available data on this topic.

Contrast Minimization With the New-Generation DyeVert Plus System for Contrast Reduction and Real-Time Monitoring During Coronary and Peripheral Procedures: First Experience.

BACKGROUND: Several strategies have been envisioned to reduce the risk of contrast-induced nephropathy, but the most modifiable approach for a treating physician is to minimize contrast administration. To date, there is no report on the use of Osprey Medical's new-generation DyeVert Plus system in coronary or peripheral applications. We aimed to appraise the role of the DyeVert Plus system inclusive of contrast reduction and real-time monitoring in a consecutive series of patients undergoing coronary or peripheral invasive procedures. METHODS: Baseline, procedural, and outcome details for patients undergoing coronary or peripheral invasive procedures were collected from our institutional database. We primarily focused on total and relative amount of contrast saved, as calculated and displayed by the DyeVert Plus system. RESULTS: The DyeVert Plus system was used in 10 patients. All procedures were successfully completed with adequate and high-quality angioscopic and angiographic images. No adverse events occurred up to discharge in any patients, with the notable exception of 1 case of asymptomatic and uneventful contrast-induced nephropathy. Average contrast volume was 79.9 ± 48.8 mL (95% confidence interval [CI], 53.2 to 109.4), thanks to an absolute saving of 55.8 ± 31.9 mL (95% CI, 39.1 to 76.7; P<.05) and a relative saving of 41.8 ± 7.3% (95% CI, 37.5 to 46.4; P<.05). Comparison of contrast volume estimates between DyeVert Plus vs manual measurements showed a minimal difference of 1.6 ± 1.9 mL (95% CI, 2.9 to 0.5; P<.05). CONCLUSION: Use of the new-generation DyeVert Plus system inclusive of contrast reduction and real-time monitoring is feasible in both coronary and peripheral applications while significantly reducing contrast volume.

Comparison of Biolimus Versus Everolimus for Drug-Eluting Stents in the Percutaneous Treatment of Infra-Inguinal Arterial Disease.

BACKGROUND: Drug-eluting stents (DES) are now considered the most promising device to treat peripheral artery disease (PAD) and minimize restenosis. There is uncertainty however on the best antirestenotic drug for such devices. In particular, biolimus (i.e. umirolimus) and everolimus are two of the most promising agents, given the extensive data in support of their coronary safety and efficacy, but their comparative effectiveness for peripheral interventions is not established. METHODS: Building upon our extensive experience in the percutaneous treatment of infra-inguinal artery disease with DES, we compared the acute and longterm outlook of patients treated with biolimus-eluting stents (BES) and everolimus-eluting stents (EES). We collected baseline, procedural and outcome details on all patients undergoing infra-inguinal BES or EES implantation. The endpoints of interest were death, amputation, revascularization, their composite, and change in Fontaine class. A total of 80 patients were included (20 treated with BES and 60 with EES). Most features were similar in the two groups, despite longer lesions in the EES group. Unadjusted analysis showed similar results irrespective of the drug used, with composite endpoint occurring, respectively, in 4 (20.0%) and 10 (16.7%) (p=0.741). RESULTS AND CONCLUSION: However, analysis with inverse probability of treatment weighting showed significant differences in the risk of revascularization (hazard ratio of BES vs EES=9.55 [95% confidence interval 2.16-42.23], p=0.003) and composite endpoint (hazard ratio=5.11 [1.33-19.62], p=0.018). In conclusion, EES appear superior to BES for endovascular therapy of infrainguinal artery disease. Dedicated randomized trials are required to definitely confirm or disprove these findings.

Radiation Dose is Significantly Reduced by Use of Contact Force Sensing Catheter During Circumferential Pulmonary Vein Isolation.

The creation of a durable radiofrequency (RF) lesion depends on several parameters, including catheter tip electrode size and composition, tip orientation, temperature, RF pulse duration, power, blood flow, and catheter to tissue contact. The development of new contact force (CF) sensor catheters has allowed the measurement of the tip to tissue CF during the RF ablation procedure. Here, we describe the clinical experience obtained using CF catheters for atrial fibrillation ablation, with a specific focus on the impact of CF technology on acute procedural data (procedure and fluoroscopy time).

Appropriate therapies predict long-term mortality in primary and secondary prevention of sudden cardiac death.

BACKGROUND: Less than 50% of patients implanted with an implantable cardioverter-defibrillator (ICD) receive device therapy during the follow-up. The aim of our study was to prospectively evaluate the predictive role of appropriate ICD therapy on long-term survival of patients implanted for primary or secondary sudden death prevention. METHODS: From 2002 to 2003, 139 consecutive patients [mean age 66±9 years, male 77%, ischemic heart disease 56%, New York Heart Association functional class >II (74%), primary prevention 74%, mean left ventricular ejection fraction 30±9%, cardiac resynchronization ICD 65%] were enrolled. We collected and evaluated device therapies for at least 18 months and recorded survival status for more than 5 years. RESULTS: Over a median follow-up of 18 months, 54 (39%) patients received at least one ICD intervention, with 28 patients receiving only appropriate ICD therapies, 13 only inappropriate therapies and 13 receiving both therapies. At a mean follow-up of 63±12 months, 30 deaths occurred in 130 patients (23%); for nine patients, we had no survival status information. Death was classified as cardiac in 22 (73%) patients, the most common cause was progressive heart failure. In a Cox proportional regression model, an appropriate ICD therapy was associated with a significant increase in the subsequent risk of death (hazard ratio 3.02, P=0.003). CONCLUSION: In patients implanted with ICD or cardiac resynchronization therapy with ICD devices, for primary or secondary sudden cardiac death prevention, appropriate ICD therapy predicts a three-fold greater risk of death.