The role of teriflunomide in Multiple Sclerosis patient: an observational study.

Teriflunomide is a drug with immunosuppressive and selective immunomodulatory action, characterized by anti-inflammatory and antiproliferative properties. Several clinical studies have demonstrated the efficacy and safety of this drug in Multiple Sclerosis, estimating a significant improvement in cognitive performance.The aim of our study is to evaluate the effects of teriflunomide by analysing the correlation between brain atrophy and the general cognitive profile and evaluating long-term changes. The effect of teriflunomide was studied in 30 patients with multiple sclerosis and 30 control subjects. Patients underwent a full cognitive profile assessment using the Brief Repeatable Battery of Neuropsychological Tests and a neuroimaging examination with a 3.0 T working scanner.Our results suggested that treatment with teriflunomide could potentially not only slow down the accumulation of microstructural tissue damage in Grey Matter and With Matter, but also better preserve the cognitive profile, particularly by highlighting the benefits in the memory domain. Thanks to drug therapy, brain volume in our patients has remained constant, leading to improvements in memory, indicating teriflunomide as a neuroprotective potential and further strengthening the evidence of a link between loss of brain volume and cognitive impairment.

Neuropsychological Disability in the Case of Natalizumab-Related Progressive Multifocal Leukoencephalopathy.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a viral disease characterized by progressive damage or inflammation of the cerebral white matter that can be encountered in patients with multiple sclerosis (MS). There are cases of PML caused by pharmacological agents including natalizumab. Therefore, in patients treated with this drug, early identification of PML allows changes in the treatment plan, reducing the risks of morbidity and mortality. CASE PRESENTATION: We reported the case of a 57-year-old female diagnosed with relapsing-remitting MS, who presented with PML related to natalizumab. The patient presented with change in behavioral, radiological abnormalities in the left parieto-temporal lobes. We described the longitudinal course of PML, from the diagnosis until the patient's death, documenting the progressive deterioration of her cognitive functioning, supported by changes on sequential brain scans and neurophysiological data. CONCLUSION: The neuropsychological impairment documented in this case study expands the range of treatment-related complications associated with natalizumab, and provides evidence that occurrence of "atypical" cognitive deficits in MS may support the early diagnosis of PML.

Accuracy of the PARIS score and PCI complexity to predict ischemic events in patients treated with very thin stents in unprotected left main or coronary bifurcations.

BACKGROUND: The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed. METHODS: The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents. RESULTS: After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI. CONCLUSIONS: In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

Does the left circumflex coronary artery location impact on the success of chronic total occlusion recanalization? A single-center cohort study.

We sought to determine whether the chronic total occlusions (CTO) recanalization results differ between circumflex artery (CX) and other coronary arteries in our center. The study dataset encompassed 428 consecutive procedures. J-CTO score was highest in the right coronary artery (RCA) and lowest in CX lesions. After adjusting for the J-CTO score, age, body mass index, baseline creatinine, diabetes, dyslipidemia and hypertension the odds ratio for procedural success in CX compared to the other arteries was not statistically significant. We found no difference in success rates of recanalizing CTO in CX compared to other coronary arteries.

When antegrade microcatheter does not follow: The "facilitated tip-in technique".

The introduction of retrograde techniques in percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) has significantly improved the success rates. After crossing the CTO lesion in the retrograde approach, wire externalization is a pivotal step to complete the PCI. Many techniques have been described to accomplish externalization in different scenarios of increasing difficulty. We describe the novel "facilitated tip-in technique" which involves the insertion of the back end of an extra-guidewire into and through the antegrade microcatheter (MC) in order to increase antegrade support and overcome demanding CTO cases where, even after successful tip-in technique, the antegrade MC does not cross the CTO segment.

Conventional vascular access site approach versus fully trans-wrist approach for chronic total occlusion percutaneous coronary intervention: a multicenter registry.

OBJECTIVES: To evaluate the incidence of vascular complication and major bleeding in patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) with a fully trans-wrist access (TWA) approach versus a conventional approach based on trans-femoral access (TFA). BACKGROUND: TFA is the preferred vascular access in CTO PCI, but it has been associated with a non-negligible risk of complications. METHODS: This retrospective registry included all patients undergoing CTO PCI at five institutions between July 2011 and October 2018. Patients were divided into two groups: Conventional (patients treated with at least one TFA) and Fully TWA (subjects exclusively treated with one or two TWA). The primary safety endpoint was a composite of vascular complications and major bleeding. The primary efficacy endpoint was procedural success. RESULTS: We included 1,900 patients (Conventional n = 1,496 and Fully TWA n = 404). Conventional patients showed higher occlusion complexity (J-CTO score 2.1 ± 1.2 vs. 1.5 ± 1.1, p < .001). Procedural success showed no significant difference between both groups (85.7 vs. 83.0%, p = .17). The primary safety endpoint occurred more frequently in the Conventional group (10.3 vs. 4.5%, p < .001), driven by vascular complications (9.4 vs. 3.7%, p < .001). On multivariate analysis, not using a Fully TWA approach was an independent predictor of the study endpoint, after adjusting for age, sex, diabetes, body mass index, chronic kidney disease, prior coronary artery bypass graft, and J-CTO score. CONCLUSIONS: Embracing a Fully TWA approach for CTO PCI might be associated with lower incidence of a composite endpoint of vascular complications and major bleeding, compared with a Conventional approach.

Impact of structural features of very thin stents implanted in unprotected left main or coronary bifurcations on clinical outcomes.

OBJECTIVES: To evaluate the independent clinical impact of stent structural features in a large cohort of patients undergoing unprotected left main (ULM) or coronary bifurcation percutaneous coronary intervention (PCI) with a range of very thin strut stents. BACKGROUND: Clinical impact of structural features of contemporary stents remains to be defined. METHODS: All consecutive patients enrolled in the veRy thin stents for patients with left mAIn or bifurcatioN in real life (RAIN) registry were included. The following stent structural features were studied: antiproliferative drugs (everolimus vs. sirolimus vs. zotarolimus), strut material (platinum-chromium vs. cobalt-chromium), polymer (bioresorbable vs. durable), number of crowns (<8 vs. ≥8) and number of connectors (<3 vs. ≥3). For small diameter stents (≤2.5 mm), struct thickness (74 vs. 80/81 µm) was also tested. Target lesion failure (TLF), a composite of target lesion revascularization and stent thrombosis, was the primary endpoint. Multivariate analysis was performed with Cox regression models. RESULTS: Out of 2,707 patients, 110 (4.1%) experienced a TLF event after 16 months (12-18). After adjustment for confounders, an increased number of connectors (adjusted hazard ratio [adj-HR] 0.62, 95% confidence interval (CI) 0.39-0.99, p = .04) reduced risk of TLF, driven by stents with ≥2.5 mm diameter (HR 0.54, 95% CI 0.32-0.93, p = .02). This independent relationship was lost for stents with diameter <2.5 mm, where only strut thickness appeared to impact. Conversely, no independent relationship of polymer type, number of crowns, and the specific limus-family eluted drug with outcomes was observed. CONCLUSIONS: Among a range of contemporary very thin stent models, an increased number of connectors improved device-related outcomes in this investigated high-risk procedural setting.

Comparison of bioresorbable vs durable polymer drug-eluting stents in unprotected left main (from the RAIN-CARDIOGROUP VII Study).

BACKGROUND: There are limited data regarding the impact of bioresorbable polymer drug eluting stent (BP-DES) compared to durable polymer drug eluting stent (DP-DES) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. METHODS: In the RAIN registry (ClinicalTrials NCT03544294, june 2018 retrospectively registered) patients with a ULM or bifurcation stenosis treated with PCI using ultrathin stents (struts thinner than 81 µm) were enrolled. The primary endpoint was the rate of target lesion revascularization (TLR); major adverse cardiovascular events (MACE, a composite of all-cause death, myocardial infarction, TLR and stent thrombosis) and its components, along with target vessel revascularization (TVR) were the secondary ones. A propensity score with matching analysis to compare patients treated with BP-DES versus DP-DES was also assessed. RESULTS: From 3001 enrolled patients, after propensity score analysis 1400 patients (700 for each group) were selected. Among them, 352 had ULM disease and 1048 had non-LM bifurcations. At 16 months (12-22), rates of TLR (3.7% vs 2.9%, p = 0.22) and MACE were similar (12.3% vs. 11.6%, p = 0.74) as well as for the other endpoints. Sensitivity analysis of outcomes after a two-stents strategy, showed better outcome in term of MACE (20.4% vs 10%, p = 0.03) and TVR (12% vs 4.6%, p = 0.05) and a trend towards lower TLR in patients treated with BP-DES. CONCLUSION: In patients with bifurcations or ULM treated with ultrathin stents BP-DES seems to perform similarly to DP-DES: the trends toward improved clinical outcomes in patients treated with the BP-DES might potentially be of value for speculating the stent choice in selected high-risk subgroups of patients at increased risk of ischemic events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03544294. Retrospectively registered June 1, 2018.

Coronary lithotripsy for failed rotational atherectomy, cutting balloon, scoring balloon, and ultra-high-pressure non-compliant balloon.

Calcified and undilatable stenosis still represents a challenge in percutaneous coronary interventions (PCI), due to the higher risk of suboptimal result with consequent worse clinical outcomes. Unfortunately, the dedicated technologies and devices, such as specialized balloon and atherectomy systems, do not always provide adequate plaque modification and optimal vessel preparation allowing optimal stent delivery. The intravascular lithotripsy (IVL) is a technology derived from urology that has been tested in peripheral and coronary calcified plaques, with promising preliminary results. We present a case of a patient undergoing planned PCI of the right coronary artery targeting an undilatable lesion, already resistant to both specialized balloons and rotational atherectomy. Using the IVL system, we were able to break the calcium, guarantying optimal stent expansion with good final result.

Anxiety and Perception of Disease Control in Multiple Sclerosis Subjects Treated with Natalizumab.

Multiple sclerosis subjects treated with natalizumab face anxiety about developing progressive multifocal leukoencephalopathy (PML), besides the psychological distress caused by the disease. The aim of this study is to investigate whether increasing the frequency of neurological and nuclear magnetic resonance screening may affect anxiety and the perception of disease control in patients treated with natalizumab. A total of 62 relapsing-remitting multiple sclerosis patients were recruited from 2019 to 2020. All patients received conventional infusion treatments with natalizumab, along with a screening protocol for PML. Three clinical assessments were considered: at the beginning of the study (T0), after 3 months (T1) and after 6 months (T2). Patients were classified into three levels of risk, where level 1 represented a low risk of PML and level 3 a high risk. This classification determined treatment and screening protocol, i.e., the frequency of performing the Stratify test and the brain 3T NMR exam, as well as the frequency of infusion treatments. Anxiety and perception of disease control were assessed at T0, T1, and T2 by a skilled psychologist. The Friedman test and the Wilcoxon signed-rank test were used to compare outcomes at baseline with the two follow-ups. Statistical test results showed that the risk of PML (per 1000 patients) was significantly lower in women than in men (W = 198.5; p = 0.01). Moreover, significant differences between baseline and the two follow-ups were found, both for anxiety (F(2) = 122.6, p < 0.001) and for perception of disease control (F(2) = 123.5, p < 0.001). In both cases, there was significant improvement between baseline (T0) and the end of the study (T2) in any risk level (p < 0.001). An increase in the number of follow-ups, as well as an increase in instrumental investigations, might have a positive effect on both anxiety and the perception of disease control. However, there are many variables involved in the disease process that have an impact on patients' psychological well-being. Therefore, further and more extensive studies are necessary to evaluate how, and how much, each variable impacts the disease course.

Ultrasound- Versus Fluoroscopy-Guided Femoral Access for Percutaneous Coronary Intervention of Chronic Total Occlusions: Insights From FOUND BLOOD CTO Registry.

OBJECTIVE: To compare vascular complications in patients undergoing percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) using ultrasound guidance (USG) versus fluoroscopy guidance (FSG) for femoral access. BACKGROUND: In patients undergoing PCI, using the arterial femoral access increases the risk of vascular complications compared using the radial access. USG reduces time to access, number of attempts, and vascular complications compared with FSG, but the efficacy of USG has never been tested in the setting of CTO-PCI. METHODS: A total of 197 patients undergoing CTO-PCI using at least a femoral vascular access from November 2015 to September 2020 were screened. The primary outcome was a composite of local hematoma, pseudoaneurysm, retroperitoneal hemorrhage, arteriovenous fistula or hemoglobin drop ≥3 g/dL during hospitalization. The independent association between USG and the primary outcome of interest was explored. RESULTS: The primary outcome occurred in 17.3% of patients. Patients in the USG group had a significantly lower incidence of vascular complications compared with patients in the FSG group (8.5% vs. 21.0%, p = 0.039), driven by a reduction of localized hematomas (3.4% vs 13.0%, p = 0.042). After adjustment for type of CTO approach and heparin dose, USG was significantly associated with a reduced relative risk of the composite primary outcome (adjusted odds ratio 0.16, 95% confidence interval 0.05 to 0.51; p = 0.002). CONCLUSION: USG in CTO-PCI is associated with a decreased risk of vascular complications, primarily driven by a reduction in local hematomas, especially in complex CTO-PCI where the larger use of heparin increases the risk of vascular complications.

Comparison of ECMO vs ECpella in Patients With Non-Post-Pericardiotomy Cardiogenic Shock: An Updated Meta-Analysis.

INTRODUCTION: The impact of Impella and ECMO (ECPELLA) in cardiogenic shock (CS) remains to be defined. The aim of this meta-analysis is to evaluate the benefit of ECPELLA compared to VA-ECMO in patients with non post-pericardiotomy CS. METHODS: All studies reporting short term outcomes of ECpella or VA ECMO in non post-pericardiotomy CS were included. The primary endpoint was 30-day mortality. Vascular and bleeding complications and LVAD implantation/heart transplant within 30-days were assessed as secondary outcomes. RESULTS: Of 407 studies identified, 13 observational studies (13,682 patients, 13,270 with ECMO and 412 with ECpella) were included in this analysis. 30-day mortality was 55.8% (51.6-59.9) in the VA-ECMO group and 58.3% (53.5-63.0) in the ECpella group. At meta-regression analysis the implantation of IABP did not affect mortality in the ECMO group. The rate of major bleeding in patients on VA-ECMO and ECpella support were 21.3% (16.9-26.5) and 33.1% (25.9-41.2) respectively, while the rates of the composite outcome of LVAD implantation and heart transplantation within 30-days in patients on VA-ECMO and ECpella support were 14.4% (9.0-22.2) and 10.8%. When directly compared in 3 studies, ECpella showed a positive effect on 30-day mortality compared to ECMO (OR: 1.81: 1.039-3.159). CONCLUSION: Our data suggest that ECpella may reduce 30-day mortality and increase left ventricle recovery, despite increased of bleeding rates.

Prediction of All-Cause Mortality Following Percutaneous Coronary Intervention in Bifurcation Lesions Using Machine Learning Algorithms.

Stratifying prognosis following coronary bifurcation percutaneous coronary intervention (PCI) is an unmet clinical need that may be fulfilled through the adoption of machine learning (ML) algorithms to refine outcome predictions. We sought to develop an ML-based risk stratification model built on clinical, anatomical, and procedural features to predict all-cause mortality following contemporary bifurcation PCI. Multiple ML models to predict all-cause mortality were tested on a cohort of 2393 patients (training, n = 1795; internal validation, n = 598) undergoing bifurcation PCI with contemporary stents from the real-world RAIN registry. Twenty-five commonly available patient-/lesion-related features were selected to train ML models. The best model was validated in an external cohort of 1701 patients undergoing bifurcation PCI from the DUTCH PEERS and BIO-RESORT trial cohorts. At ROC curves, the AUC for the prediction of 2-year mortality was 0.79 (0.74-0.83) in the overall population, 0.74 (0.62-0.85) at internal validation and 0.71 (0.62-0.79) at external validation. Performance at risk ranking analysis, k-center cross-validation, and continual learning confirmed the generalizability of the models, also available as an online interface. The RAIN-ML prediction model represents the first tool combining clinical, anatomical, and procedural features to predict all-cause mortality among patients undergoing contemporary bifurcation PCI with reliable performance.

Using the coronary lithotripsy system for coronary artery disease.

Severe coronary artery calcification increases percutaneous treatment complexity and the risk of intraprocedural complications, affecting acute and long-term outcomes. Current use of specialty balloons and atherectomy technologies is limited due to the higher risk of complications, degree of technical difficulty and operator experience. Intravascular lithotripsy (IVL) is a novel technology for severe calcified coronary artery disease that facilitates vessel preparation, enhancing vessel compliance. IVL system emits sonic waves that penetrate through vascular layers and disrupt both superficial and deep calcium, leaving the soft tissue unharmed. The purpose of the present review is to provide a summary of the evidence currently available on this therapy, including a practical description of the components and function of the shockwave coronary IVL system.

[Devices for the prevention of contrast-induced acute kidney injury in interventional cardiology]. / Dispositivi medici per la prevenzione del danno renale acuto da mezzo di contrasto in cardiologia interventistica.

Contrast-induced acute kidney injury (CI-AKI) consists in acute decline in renal function following iodinated contrast media exposure. It has a significant impact on long-term prognosis and mortality, development of chronic kidney disease and on the rate of hospitalization due to cardiovascular or renal events. Anamnestic and procedural aspects linked to higher risk of CI-AKI have been investigated and new devices have been designed in order to prevent it. This paper deals with CI-AKI in interventional cardiology, focusing on patients' risk stratification, contrast media agent selection and contrast media volume reduction strategies, in order to suggest a standardized algorithm.

Impact of stent thickness on clinical outcomes in small vessel and bifurcation lesions: a RAIN-CARDIOGROUP VII sub-study.

BACKGROUND: The clinical impact of stent strut thickness in coronary bifurcation lesions in small vessels has not been assessed in a real-world population. METHODS: All 506 patients enrolled in the RAIN study, undergoing PCI in a vessel with a diameter 2.5 mm or less were retrospectively evaluated and divided into two groups according to stent strut thickness: 74 µm (n = 206) versus 81 µm (n = 300); 87.1% of the lesions involved bifurcations. TLF [defined as a composite of myocardial infarction (MI) and target lesion revascularization (TLR)] was the primary endpoint, with MACE (a composite of death, MI and TLR), its components and stent thrombosis the secondary endpoint. RESULTS: After 16 (14-18) months, a lower incidence of TLF (4.3 vs. 9.8%, P = 0.026) and ST (1.0 vs. 3.0%, P = 0.042) was seen in the 74 µm group, whereas MACE occurred in 60 of 506 patients, with no statistical difference between the two groups (9.7 vs. 13.3%, P = 0.070). At multivariate analysis, chronic renal failure increased the risk of TLF while thinner strut was an independent protective factor (hazard ratio 0.51, CI 0.17-0.85, P = 0.005). CONCLUSION: In this real-world population, patients being treated for small vessels lesions with thinner strut stents had lower rates of TLF, MI and ST.

Performance of Thin-Strut Stents in Non-Left Main Bifurcation Coronary Lesions: A RAIN Subanalysis.

OBJECTIVES: This study assesses the safety and efficacy of thin-strut stents in non-left main (non-LM) bifurcation coronary lesions. BACKGROUND: Thinner struts of recent drug-eluting stent (DES) devices are associated with improved outcomes, but data about their performance in challenging scenarios are scant. METHODS: RAIN was a retrospective multicenter registry enrolling patients with coronary bifurcation lesions or left main (LM) disease treated with thin-strut DESs. Target-lesion revascularization (TLR) was the primary endpoint, while major adverse clinical event (MACE) rate, a composite of all-cause death, myocardial infarction (MI), target-vessel revascularization (TVR), TLR, and stent thrombosis (ST), and its single components were the secondary endpoints. Multivariable analysis was performed to identify predictors of TLR. Outcome incidences according to stenting strategy (provisional vs 2-stent technique), use of final kissing balloon (FKB), and intravascular ultrasound/optical coherence tomography optimization were further investigated in prespecified subanalyses. RESULTS: A total of 1803 patients (59% acute coronary syndrome, 41% stable coronary artery disease) with non-LM bifurcations were enrolled. After a median follow-up of 12 months, TLR incidence was 2.5% (2.2% for provisional stenting and 3.5% for 2-stent technique). MACE rate was 9.4% (all-cause death, 4.1%; MI, 3.2%; TVR, 3.7%; definite ST, 1.1%). After multivariable adjustment, postdilation (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15-0.71; P<.01) and provisional stenting (HR, 0.62; 95% CI, 0.55-0.89; P=.03) were associated with lower TLR rates. FKB was associated with a lower incidence of TLR in the 2-stent subgroup (P=.03). Intracoronary imaging had no significant impact on the primary endpoint. CONCLUSIONS: Thin-strut DES options represent an effective choice in bifurcation lesions. Postdilation and provisional stenting are associated with a reduced risk of TLR. FKB should be recommended in 2-stent techniques.

Cracking the Plaque With Coronary Lithotripsy: Mechanistic Insights From Optical Coherence Tomography.

Coronary lithoplasty is a promising technique that can overcome issues regarding the treatment of undilatable, heavily calcified, de novo, and in-stent restenotic lesions, allowing plaque modification and successful stent deployment, as demonstrated by intravascular imaging.

[Treatment of coronary artery calcification: state of the art]. / Trattamento della malattia coronarica calcifica: stato dell'arte.

Coronary artery calcification enhances percutaneous treatment complexity, increasing the likelihood of procedural failure and complications and affecting acute and long-term outcomes. In order to deal with such lesions, several devices and technologies, including balloons, atherectomy and intravascular lithotripsy, have been developed. The combination of the aforementioned technologies and the guidance of intracoronary imaging can help skilled interventional cardiologists in achieving better acute and long-term results in this setting. The purpose of the present review is to provide an appraisal of the devices dedicated to the treatment of calcified lesions, including the description of components and function and how to integrate them into a practical, standardized approach.

[Management of coronary perforations during angioplasty]. / Gestione delle perforazioni coronariche durante angioplastica coronarica.

Coronary perforation represents a terrible complication of percutaneous coronary intervention (PCI) which, if not promptly recognized and treated, can lead to catastrophic consequences for the patient. Hence, acquisition of the basic techniques for the treatment of coronary perforations is critical for the interventional cardiologist in order to safely perform PCIs. Although the incidence of coronary perforations remains low during PCI, it is possible to recognize some subgroups of patients and some types of coronary lesions, such as chronic coronary total occlusions, that are associated with increased risk. The treatments currently available depend on the type and site of coronary perforation, therefore timely recognition is of paramount importance in order to be able to quickly establish the most appropriate treatment.