Old age: the crown of life, our play's last act. Question and answers on older patients undergoing allogeneic hematopoietic cell transplantation.

PURPOSE OF REVIEW: Several studies showed that age alone should not be used as an arbitrary parameter to exclude patients from allogeneic hematopoietic cell transplantation (HCT). The accessibility to allogeneic HCT programs for older patients with hematological diseases is growing up constantly. The Center for International Blood and Marrow Transplant Research has recently shown that over 30% of allogeneic HCT recipients are at least 60 years old and that nearly 4% are aged 70 or more. Historically, the use of allogeneic HCT among elderly patients has been limited by age restrictions, reflecting physicians' concerns regarding prohibitive transplant-related mortality and HCT-associated morbidity. RECENT FINDINGS: The introduction of reduced intensity/toxicity conditioning regimens has allowed transplant Centers to carry out allogeneic HCT on patients previously considered not ideal candidates. The integration of specific risk scores could lead to better capture mental and physical frailties of older patients. Older adults less frequently have available medically fit siblings, able to donate, so, unrelated donors, familial haploidentical donors or umbilical cord blood grafts could potentially abrogate such a difficulty, allowing the curative potential of allogeneic HCT. SUMMARY: The appropriate assessing of allogeneic HCT feasibility for elderly patients should be the resonate application of different clinical and biological principles.

Postprocedural trans-mitral gradient in patients with degenerative mitral regurgitation undergoing mitral valve transcatheter edge-to-edge repair.

BACKGROUND: The relationship between high postprocedural mean gradient (ppMG) and clinical events following mitral valve transcatheter edge-to-edge repair (MV-TEER) in patients with degenerative mitral regurgitation (DMR) is still debated. AIM: The purpose of this study was to evaluate the effect of elevated ppMG after MV-TEER on clinical events in patients with DMR at 1-year follow-up. METHODS: The study included 371 patients with DMR treated with MV-TEER enrolled in the "Multi-center Italian Society of Interventional Cardiology (GISE) registry of trans-catheter treatment of mitral valve regurgitation" (GIOTTO) registry. Patients were stratified in tertiles according to ppMG. Primary endpoint was a composite of all-cause death and hospitalization due to heart failure at 1-year follow-up. RESULTS: Patients were stratified as follows: 187 with a ppMG ≤ 3 mmHg, 77 with a ppMG > 3/=4 mmHg, and 107 with a ppMG > 4 mmHg. Clinical follow-up was available in all subjects. At multivariate analysis, neither a ppMG > 4 mmHg nor a ppMG ≥ 5 mmHg were independently associated with the outcome. Notably, the risk of elevated residual MR (rMR > 2+) was significantly higher in patients belonging to the highest tertile of ppMG (p = 0.009). The association of ppMG > 4 mmHg and rMR ≥ 2+ was strongly and independently associated with adverse events (hazard ratio: 1.98; 95% confidence interval: [1.10-3.58]). CONCLUSIONS: In a real-world cohort of patients suffering DMR and treated with MV-TEER, isolated ppMG was not associated with the outcome at 1-year follow-up. A high proportion of patients showed both elevated ppMG and rMR and their combination appeared to be a strong predictor of adverse events.

Instantaneous wave-free ratio-guided revascularization of nonculprit lesions in STEMI patients with multivessel coronary disease: The WAVE registry.

BACKGROUND: Complete revascularization (CR) of nonculprit lesions (NCL) is strongly recommended in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD), but no definitive evidence is available regarding which diagnostic strategy should be preferred. Instantaneous wave-free ratio (iFR) has never been investigated in this setting. We aimed to describe clinical outcomes of a cohort of patients undergoing iFR-guided CR. METHODS: Following primary percutaneous coronary intervention (PCI), consecutive patients with STEMI and intermediate NCL were enrolled and destinated to an iFR-guided CR. NCL with iFR ≤ 0.89 underwent PCI while NCL with iFR > 0.89 were deferred. The primary endpoint was NC target lesion failure (NC-TLF) and the secondary endpoint was major adverse cardiovascular events (MACE), at 1-year follow-up. RESULTS: Overall, 209 patients were enrolled (ischemic iFR = 83; nonischemic iFR = 126). Patients with ischemic iFR showed a higher prevalence of traditional cardiovascular risk factors and angiographically determined three-vessel disease. In the entire cohort, NC-TLF and MACE occurred in 6.7% and 10.5% of patients, respectively. Compared to the deferred group, patients with ischemic iFR experienced significantly higher rates of both NC-TLF (3.2% vs. 12.1%; p = 0.021) and MACE (7.1% vs. 16.9%; p = 0.041). These results were mostly driven by increased rates of NC-TLF PCI and further revascularizations in this latter group, while no differences were evident in terms of nonfatal myocardial infarction or death. At multivariable analysis, the strongest predictor of MACE was symptom onset to balloon time (HR = 1.17 [95% CI: 1.04-1.31], p = 0.008). CONCLUSIONS: In our study enrolling STEMI patients with MVD, iFR assessment was feasible and safe. PCI-deferring according to iFR evaluation of NCL was associated with low rates of adverse events. Further randomized studies are needed to investigate the effectiveness of iFR-guided revascularization compared to current practice in this setting.

Clinical outcomes and predictors in patients with previous cardiac surgery undergoing mitral valve transcatheter edge-to-edge repair.

BACKGROUND: Mitral-valve transcatheter edge-to-edge repair (MV-TEER) is recommended in patients with severe functional mitral regurgitation (FMR) and in those with degenerative mitral regurgitation (DMR) not eligible to traditional surgery. Patients with a history of previous cardiac surgery are considered at high risk for surgical reintervention, but data are lacking regarding procedural and clinical outcomes. OBJECTIVE: aim of this study was to assess the efficacy and clinical results of MV-TEER in patients with previous cardiac surgery enrolled in the "multicentre Italian Society of Interventional Cardiology registry of transcatheter treatment of mitral valve regurgitation" (GIOTTO). METHODS: Patients with previous coronary artery bypass grafting (CABG), surgical aortic valve replacement (AVR), or mitral valve repair (MVR) were included. Those with multiple or combined previous cardiac surgeries were excluded. Clinical follow-up was performed at 30 days, 1 year, and 2 years. The primary endpoint was a composite of death or rehospitalization at 1- and 2-year follow-ups. RESULTS: A total of 330 patients enrolled in the GIOTTO registry were considered (CABG 77.9%, AVR 14.2%, and MVR 7.9%). Most patients showed FMR (66.9%), moderate reduction of left ventricular (LV) ejection fraction, and signs of LV dilation. Procedural and device successes were 94.8% and 97%. At 1 and 2 years, the composite endpoint occurred are 29.1% and 52.4%, respectively. The composite outcome rates were similar across the three subgroups of previous cardiac surgery (p = 0.928) and between the FMR and DMR subgroups (p = 0.850) at 2 years. In a multivariate analysis, residual mitral regurgitation (rMR) ≥2+ was the main predictor of adverse events at 1 year (hazard ratio: 1.54 [95% confidence interval, CI: 1.00-2.38]; p = 0.050). This association was confirmed at 2 years of Kaplan-Meier analysis (p = 0.001). CONCLUSIONS: MV-TEER is effective in these patients, regardless of the subtype of previous cardiac surgery and the MR etiology. An rMR ≥2+ is independently associated with adverse outcomes at 1-year follow-up.

Predictors of optimal procedural result after transcatheter edge-to-edge mitral valve repair in secondary mitral regurgitation.

BACKGROUND: Procedural success after transcatheter edge-to-edge mitral valve repair (TEER) is defined as a reduction of mitral regurgitation (MR) degree to

Long-term clinical outcome and performance of transcatheter aortic valve replacement with a self-expandable bioprosthesis.

AIMS: In the last decade, transcatheter aortic valve (TAV) replacement determined a paradigm shift in the treatment of patients with severe symptomatic aortic stenosis. Data on long-term TAV performance are still limited. We sought to evaluate the clinical and haemodynamic outcomes of the CoreValve self-expandable valve up to 8-year follow-up (FU). METHODS AND RESULTS: Nine hundred and ninety inoperable or high-risk patients were treated with the CoreValve TAV in eight Italian Centres from June 2007 to December 2011. The median FU was 4.4 years (interquartile range 1.4-6.7 years). Longest FU reached 11 years. A total of 728 died within 8-year FU (78.3% mortality from Kaplan-Meier curve analysis). A significant functional improvement was observed in the majority of patients and maintained over time, with 79.3% of surviving patients still classified New York Heart Association class ≤ II at 8 years. Echocardiographic data showed that the mean transprosthetic aortic gradient remained substantially unchanged (9 ± 4 mmHg at discharge, 9 ± 5 mmHg at 8 years, P = 0.495). The rate of Grade 0/1 paravalvular leak was consistent during FU with no significant change from post-procedure to FU ≥5 years in paired analysis (P = 0.164). Structural valve deterioration (SVD) and late bioprosthetic valve failure (BVF) were defined according to a modification of the 2017 EAPCI/ESC/EACTS criteria. In cumulative incidence functions at 8 years, moderate and severe SVD were 3.0% [95% confidence interval (CI) 2.1-4.3%] and 1.6% (95% CI 0.6-3.9%), respectively, while late BVF was 2.5% (95% CI 1.2-5%). CONCLUSION: While TAVs are questioned about long-term performance and durability, the results of the present research provide reassuring 8-year evidence on the CoreValve first-generation self-expandable bioprosthesis.

Instantaneous wave-free ratio and fractional flow reserve for the assessment of nonculprit lesions during the index procedure in patients with ST-segment elevation myocardial infarction: The WAVE study.

BACKGROUND: Functional assessment of non-infarct-related artery lesions during primary percutaneous coronary intervention (PCI) might be useful to avoid revascularization of nonsignificant stenosis and staged procedures, thus reducing hospital stay. We aimed to assess the diagnostic performance of instantaneous wave-free ratio (iFR) as compared with fractional flow reserve (FFR) in this setting. METHODS: In the WAVE study, a prospective, observational, single-center registry (NCT02869906), paired iFR and FFR measurements were performed at the level of non-IRA lesions in patients with ST-segment elevation myocardial infarction both during primary PCI and during staged procedures (5-8 days after). RESULTS: Paired iFR and FFR measurements were available for 66 non-IRA lesions in 50 patients. The iFR and FFR values of non-IRA lesions did not change significantly between the index and staged procedure. Bland-Altman analysis did not show systematic bias for either iFR or FFR repeated measures. Receiver operating characteristic curve analysis showed high accuracy of iFR to identify positive (≤0.80) FFR measurements in the index procedure with an area under the curve of 0.95. A cutoff of ≤0.89 for iFR in the index procedure had the best combination of sensitivity (95%) and specificity (90%) with positive and negative predictive values of 86% and 97%, respectively. Finally, iFR measured during the index procedure was significantly correlated with FFR (r=0.71, r2=0.51; P<.0001). CONCLUSIONS: The WAVE study shows that iFR yields similar diagnostic accuracy to FFR in functional evaluation of non-IRA stenosis in patients with STEMI and multivessel CAD, with the advantage of being adenosine free.

A propensity score matched comparative study between paclitaxel-coated balloon and everolimus-eluting stents for the treatment of small coronary vessels.

OBJECTIVES: To compare the long-term clinical outcomes of paclitaxel drug-coated-balloons (DCB) and everolimus-eluting-stents (EES) following the treatment of de novo small vessel coronary artery disease. BACKGROUND: It is currently unclear whether treatment of de novo small vessel coronary disease with DCB is comparable to second generation drug-eluting stents, which are the current standard of care. METHODS: The present study enrolled 90 patients with small vessel coronary disease from the DCB treatment arm of the BELLO (Balloon Elution and Late Loss Optimization) trial and 2,000 patients treated with EES at the San Raffaele Scientific Institute. Propensity score matching was performed to adjust for differences in baseline clinical and angiographic characteristics, yielding a total of 181 patients: 90 patients with 94 lesions receiving DCB and 91 patients with 94 lesions receiving EES. Major adverse cardiac events (MACE) were defined as the composite of cardiac death, recurrent non-fatal myocardial infarction, and target vessel revascularization. RESULTS: After propensity score matching, baseline clinical and angiographic characteristics were similar between the two groups. The cumulative MACE rate at 1-year was 12.2% with DCB and 15.4% with EES (P = 0.538). Patients in the DCB group had similar TLR rates as compared to EES over the same interval (4.4% vs. 5.6%; P = 0.720). There were no cases of definite or probable stent or vessel thrombosis. CONCLUSIONS: The use of paclitaxel-DCB appears to be associated with similar clinical outcomes when compared to second-generation-EES in small coronary artery disease. The findings of this study should be confirmed with larger prospective randomized studies with longer follow-up. © 2017 Wiley Periodicals, Inc.

Treatment of mitral regurgitation.

In the elderly mitral regurgitation is very frequent and surgical correction of mitral regurgitation (MR) has often a high operative risk, consequently, over the years, different percutaneous transcatheter techniques have been developed as a valid alternative to surgery. The edge-to-edge repair with the MitraClip device has gained a wide clinical application, supported by several studies, both randomize trials and registries. It is indicated in functional MR as in degenerative MR. The outcome is usually positive, resulting in a reduction of the regurgitation to grade 1+ or 2+ and an improvement in the functional class to I or II reducing hospitalizations. Its cost-effectiveness too is supported by some studies.

Effect of Abciximab Therapy in Patients Undergoing Coronary Angioplasty for Acute ST-Elevation Myocardial Infarction Complicated by Cardiogenic Shock.

BACKGROUND: The effect of abciximab on survival in patients with ST-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS) undergoing primary percutaneous coronary intervention (PCI) is not clear. METHODS AND RESULTS: We evaluated outcome in 410 consecutive patients with STEMI and CS who underwent PCI treated without (n=123) or with (n=287) abciximab. The endpoint was survival at 1-year follow-up. The predictors of death at 1 year were also investigated. The groups with and without abciximab had similar survival at 1-year follow-up. Propensity score-adjusted Cox proportional hazards model identified age (adjusted hazard ratio [HR], 1.02; 95% confidence interval [95% CI]: 1.01-1.03, P=0.001), oro-tracheal intubation (HR, 1.49; 95% CI: 1.12-1.96, P=0.05), post-PCI TIMI flow grade 0-1 (HR, 2.08; 95% CI: 1.52-2.83, P=0.0001) but not abciximab use (HR, 1.08; 95% CI: 0.70-1.60, P=0.60) as independent predictors of death at 1-year follow-up. Cox adjusted 1-year survival rates were 42.8% and 51.6%, (P=0.56) in patients treated without vs. with abciximab, respectively. CONCLUSIONS: Patients with STEMI complicated by CS undergoing PCI treated with or without abciximab have similar 1-year survival rates; age, final TIMI 0-1 and oro-tracheal intubation are predictors of death.

Impact of Transcatheter Edge-to-Edge Mitral Valve Repair on Atrial Functional Mitral Regurgitation from the GIOTTO Registry.

Atrial functional mitral regurgitation (aFMR) has a peculiar pathophysiology that may have distinctive outcomes. We investigated the impact of transcatheter edge-to-edge repair in aFMR compared with other FMR etiologies. The GIOTTO (GIse registry Of Transcatheter treatment of MR) is a multicenter, prospective study enrolling patients with symptomatic MR treated with MitraClip up to 2020. We categorized patients with FMR as aFMR, ischemic FMR (iFMR), and nonischemic ventricular FMR (niFMR). The clinical end points were defined according to the Mitral Valve Academic Research Consortium. Of 1,153 patients, 6% had aFMR, 47% iFMR, and 47% niFMR. Patients with aFMR were older, mostly women, and had a higher atrial fibrillation rate. They had better left ventricular ejection fraction and smaller left ventricular volumes, with no difference in mitral effective regurgitant orifice area. The acute device and procedural success rates were similar among the groups. At the longest available follow-up (median 478 days, interquartile range 91 to 741 days), the rate of MR ≥2+ was similar among the groups. Patients with aFMR had a lower rate of cardiovascular death and heart failure than patients with iFMR (hazard ratio [HR] 0.43, p = 0.02) and niFMR (HR 0.45, p = 0.03). The aFMR etiology remained independently associated with the composite outcome, together with postprocedural MR ≤1+ (HR 0.63, p <0.01) and peripheral arteriopathy (HR 1.82, p = 0.003). The results of this GIOTTO subanalysis suggested that aFMR is less prevalent and associated with better outcomes compared with other causes of FMR treated by transcatheter edge-to-edge repair. Postprocedural MR >1+, peripheral vasculopathy, non-aFMR were independent predictors of worse outcomes.

Impact of Pacemaker Implantation After Transcatheter Aortic Valve Replacement on Long-Term Survival in Patients With Bicuspid Aortic Valve.

Limited data are available about the impact of permanent pacemaker (PPM) implantation on long-term survival in patients with a bicuspid aortic valve (BAV) and severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR). We aimed to evaluate the long-term clinical outcomes of patients with BAV with AS who underwent periprocedural PPM implantation after TAVR with a self-expandable prosthesis. Data from patients with BAV and severe AS who underwent TAVR between April 2009 and January 2022 and followed in the framework of the One Hospital ClinicalService-CoreValve Project were collected. Patients were categorized in 2 groups according to PPM implantation after TAVR ("PPM" group) or not ("no PPM" group). The coprimary end points were all-cause death and a composite of cardiac mortality, rehospitalization because of cardiac causes, stroke, and myocardial infarction. Overall, 106 patients were considered (74 in the "no PPM" group and 32 in the "PPM" group). No statistically significant difference was found between the groups in terms of follow-up and baseline characteristics. Patients in the PPM group were more likely to show baseline conduction abnormalities (p = 0.023). Patients in the PPM group were more often treated with older generation prosthesis than those in the no PPM group (28.1% vs 5.4%, respectively, p = 0.013). At 2 years of follow-up, all-cause death in the no PPM and PPM groups occurred in 20.0% and 10.0% of patients, respectively (hazard ratio 0.37, 95% confidence interval 0.08 to 1.67). Similarly, no difference was evident for the composite end point between the 2 groups (no PPM vs PPM: 8 [14.6%] vs 6 [19.3%], hazard ratio 1.67, 95% CI 0.58 to 4.81). In conclusion, patients with severe AS and BAV treated with TAVR complicated by PPM implantation are not exposed to an increased risk of major adverse events at 2 years of follow-up.

Transcatheter Mitral Valve Repair With the MitraClip Device for Prior Mitral Valve Repair Failure: Insights From the GIOTTO-FAILS Study.

BACKGROUND: Minimally invasive mitral valve repair has a favorable risk-benefit profile in patients with significant de novo mitral regurgitation. Its role in patients with prior mitral valve repair is uncertain. We aimed to appraise the outcome of patients undergoing transcatheter edge-to-edge repair (TEER) with prior transcatheter or surgical mitral valve repair (SMVR). METHODS AND RESULTS: We queried the Italian multicenter registry on TEER with MitraClip, distinguishing naïve patients from those with prior TEER or (SMVR). Inhospital and long-term clinical/echocardiographic outcomes were appraised. The primary outcome was the occurrence of death or rehospitalization for heart failure. A total of 2238 patients were included, with 2169 (96.9%) who were naïve to any mitral intervention, 29 (1.3%) with prior TEER, and 40 (1.8%) with prior SMVR. Several significant differences were found in baseline clinical and imaging features. Respectively, device success was obtained in 2120 (97.7%), 28 (96.6%), and 38 (95.0%, P=0.261) patients; procedural success in 2080 (95.9%), 25 (86.2%), and 38 (95.0%; P=0.047); and inhospital death in 61 (2.8%), 1 (3.5%), and no (P=0.558) patients. Clinical follow-up after a mean of 14 months showed similar rates of death, cardiac death, rehospitalization, rehospitalization for heart failure, and their composite (all P>0.05). Propensity score-adjusted analysis confirmed unadjusted analysis, with lower procedural success for the prior TEER group (odds ratio, 0.28 [95% CI, 0.09-0.81]; P=0.019) but similar odds ratios and hazard ratios for all other outcomes in the naïve, TEER, and SMVR groups (all P>0.05). CONCLUSIONS: In carefully selected patients, TEER can be performed using the MitraClip device even after prior TEER or SMVR.

Prevalence and outcome of elderly and low-risk patients with degenerative mitral regurgitation undergoing transcatheter edge-to-edge repair.

AIM: The aims of this study were: i) to report the prevalence of low-risk patients with degenerative mitral regurgitation (DMR) undergoing mitral transcatheter edge-to-edge repair (M-TEER) in a real-world setting; ii) to evaluate the prognostic significance of EuroSCORE II; iii) to determine whether an optimal M-TEER provides a mortality benefit regardless of EuroSCORE-II. METHODS: We analyzed data from the GIOTTO registry that enrolled patients undergoing M-TEER in Italy. We included only patients with DMR. Two groups were defined: patients with EuroSCORE<4% and with EuroSCORE≥4%. A further stratification according to variables included in the EuroSCORE-II was made. Interaction between EuroSCORE-II and optimal procedural success was evaluated. Outcome of interest was all-cause death at 2-year. RESULTS: Among 1659 patients prospectively enrolled in the GIOTTO registry, 657 had DMR, 364 with an EuroSCORE<4% (53%) and 311 with an EuroSCORE≥4% (47%). Patients with lower EuroSCORE were older with less comorbidities. All-cause mortality was higher in patients with EuroSCORE≥ vs <4%. EuroSCORE II ≥ 4% was independently associated with an increased risk of mortality (HR 2.36, 95%CI 1.28-4.38, p = 0.007). Among variables included in the EuroSCORE-II, Left Ventricular Ejection Fraction<35% and systolic Pulmonary Artery Pressure ≥ 50mmhg were independent predictors of clinical outcome. Two-year all-cause death was higher in patients without optimal MR reduction regardless of the calculated surgical risk (p for interaction 0.3). CONCLUSION: More than half of patients with DMR undergoing M-TEER had a Euroscore<4% with a median age of 81. An optimally successful M-TEER was associated with a lower mortality regardless of EuroSCORE.

Transcatheter mitral valve repair with MitraClip: comparison of NT, NTr, and XTr Devices.

OBJECTIVES: Transcatheter edge-to-edge repair (TEER) has become an established minimally invasive treatment for significant mitral regurgitation. Ongoing refinements and the availability of different clipping devices have expanded the indications for and effectiveness of TEER, but comprehensive comparative data on this issue are lacking. In this study, we compared NT, NTr, and XTr MitraClip devices (Abbot) for TEER. METHODS: Details on patient, imaging, and procedural details, as well as short- and long-term outcomes, were sought from a national prospective clinical registry on TEER with MitraClip. The primary outcome of interest was discharge after procedural success without major clinical complications. RESULTS: A total of 2236 patients were included, 1228 (54.9%) in whom NT implantation only was attempted, 233 (10.4%) in whom NTr but not XTr implantation was attempted, and 775 (34.7%) in whom XTr implantation was attempted. Clinical and imaging features differed substantially across the groups, reflecting expanding indications with NTr and XTr devices. In-hospital outcomes were largely similar among the 3 groups, including death. Long-term unadjusted estimates of effect showed significant differences in several outcomes, including death, rehospitalization, and their composite, which demonstrated that NT was associated with more unfavorable outcomes compared with the other devices (all P less than .05). However, most differences depended on baseline features, as adjusted analysis showed no significant differences for early as well as long-term outcomes, including long-term death, rehospitalization, and their composite (all P greater than .05). CONCLUSIONS: New-generation MitraClip devices are associated with favorable procedural and clinical outcomes, despite being used in patients with more adverse features, when compared with patients treated with previous devices.

CAR+ extracellular vesicles predict ICANS in patients with B cell lymphomas treated with CD19-directed CAR T cells.

BACKGROUNDPredicting immune effector cell-associated neurotoxicity syndrome (ICANS) in patients infused with CAR T cells is still a conundrum. This complication, thought to be consequent to CAR T cell activation, arises a few days after infusion, when circulating CAR T cells are scarce and specific CAR T cell-derived biomarkers are lacking.METHODSCAR+ extracellular vesicle (CAR+EV) release was assessed in human CD19.CAR T cells cocultured with CD19+ target cells. A prospective cohort of 100 patients with B cell lymphoma infused with approved CD19.CAR T cell products was assessed for plasma CAR+EVs as biomarkers of in vivo CD19.CAR T cell activation. Human induced pluripotent stem cell-derived (iPSC-derived) neural cells were used as a model for CAR+EV-induced neurotoxicity.RESULTSIn vitro release of CAR+EVs occurs within 1 hour after target engagement. Plasma CAR+EVs are detectable 1 hour after infusion. A concentration greater than 132.8 CAR+EVs/µL at hour +1 or greater than 224.5 CAR+EVs/µL at day +1 predicted ICANS in advance of 4 days, with a sensitivity and a specificity outperforming other ICANS predictors. ENO2+ nanoparticles were released by iPSC-derived neural cells upon CAR+EV exposure and were increased in plasma of patients with ICANS.CONCLUSIONPlasma CAR+EVs are an immediate signal of CD19.CAR T cell activation, are suitable predictors of neurotoxicity, and may be involved in ICANS pathogenesis.TRIAL REGISTRATIONNCT04892433, NCT05807789.FUNDINGLife Science Hub-Advanced Therapies (financed by Health Ministry as part of the National Plan for Complementary Investments to the National Recovery and Resilience Plan [NRRP]: E.3 Innovative health ecosystem for APC fees and immunomonitoring).

Head-to-head comparison of sirolimus-eluting stent versus bare metal stent evaluation of the coronary endothelial dysfunction in the same patient presenting with multiple coronary artery lesions: the CREDENTIAL study.

OBJECTIVES: To assess the endothelial dysfunction (ED) after bare metal stents (BMS) and sirolimus eluting stents (SES) implantation in the same patient, overcoming the confounding role of individual variables. BACKGROUND: SES reduce restenosis rate compared to BMS but causes more ED. ED is a potentially unsafe phenomenon, since it is the first step in the cascade of atherosclerosis. Studies showing more pronounced ED with drug eluting stents than BMS involved different series of patients, making the comparison difficult because endothelial function (EF) is responsive to many risk factors. METHODS: we designed a prospective comparison of 6 months post-deployment EF of SES versus BMS implanted in the same patient, but in different coronary segments. Forty-eight lesions were randomly assigned on a 1:1 allocation using block sizing of 4 according to a computer-generated sequence (SAS System, Version 9.1) basis to treatment with SES or BMS. The EF was evaluated by measuring vessel diameter variation in the stented segment, before and after selective intracoronary infusion of acetylcholine (iiAch). RESULTS: In eligible patients, the relative magnitudes of major vasoconstriction were 2.6, 2.9, 4.6, and 3.1 at 5 mm proximal and 5, 10 and 20 mm distal to the stent edge. Overall, a 3.5-fold major distal vasoconstriction after iiAch of SES vs. BMS was calculated. CONCLUSIONS: in the same patients, but treating different coronary segments, SES implantation induces a higher rate of vasoconstriction compared to BMS. The increased vasoconstriction after iiAch is an indicator of ED.

Comparison between the new Gore septal and Amplatzer devices for transcatheter closure of patent foramen ovale. Short- and mid-term clinical and echocardiographic outcomes.

BACKGROUND: The ideal device for percutaneous patent foramen ovale (PFO) occlusion should provide effective closure with long-term biocompatibility and it should have a low profile without interfering with adjacent cardiac structures. Long-term data regarding safety and efficacy of the GORE Septal Occluder (GSO) are lacking. The aim of this study was to investigate the short- and mid-term clinical and echocardiographic outcomes of this device. METHODS AND RESULTS: Forty-five consecutive patients with clinically significant PFO were treated with GSO and their results were compared with those of 45 consecutive patients treated with Amplatzer PFO device (APO). Primary endpoint was the incidence of 6-month residual right-to-left shunting (rRLS). The procedural results and the recurrence of embolic events (REE) at 1 year were also investigated. No differences in terms of embolic risk profile and echocardiographic parameters were observed between the 2 groups. GSO was successfully implanted in all patients without device-related complication. In 2 patients for whom device position was not optimal, the GSO was easily retrieved and a new GSO was successfully repositioned. Immediate moderate-severe rRLS was similar in 2 groups. No cases of severe 6-month rRLS were registered. Two patients (4%) and 1 patient (2%) had moderate 6-month rRLS in the GSO and APO group, respectively (P=NS). No cases of REE were registered at 1-year follow-up. CONCLUSIONS: GSO appears a valuable alternative to Amplatzer device for PFO occlusion.

Outcomes of Patients With Very Severe Aortic Stenosis Treated With Transcatheter Aortic Valve Implantation.

Symptoms of aortic stenosis (AS) are not proportional to its severity and patients with very severe AS (VSAS) remain asymptomatic for a long time. The appropriate time for intervention in patients with VSAS and the effects of transcatheter aortic valve implantation (TAVI) on left ventricular hypertrophy (LVH) remain debated. Our aim was to compare the procedural and 30-day outcomes of TAVI between patients with VSAS and patients with severe AS (SAS) and the changes in LVH. We selected patients with an aortic peak velocity ≥5 m/s (VSAS) and those with aortic peak velocity 4 to 5 m/s (SAS) treated with TAVI. Patients with reduced left ventricular ejection fraction (<45%) were excluded. The primary end point was the incidence of all-cause death at 30 days. The secondary end points included the 30-day incidence of cardiac death, cardiac rehospitalization, and stroke/transient ischemic attack and the changes in LVH from baseline to 30 days. A total of 102 patients in the VSAS group and 535 in the SAS group were included. Patients in the VSAS group had a thicker septal wall (p <0.001) and a higher Agaston score (p <0.001) and calcium volume (p = 0.007). No differences were observed regarding the primary and secondary clinical end points. However, patients with VSAS showed a significantly greater improvement in concentric LVH, although the prevalence of concentric LVH remained higher than in patients with SAS. TAVI in patients with VSAS showed similar procedural and clinical outcomes to patients with SAS and experienced a more pronounced improvement in the prevalence of concentric LVH.

One-Month Dual Antiplatelet Therapy in Patients With Chronic and Acute Coronary Syndromes Treated With Bioresorbable Polymer Everolimus-Eluting Stents.

There is a paucity of data regarding the safety of a 1-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) presenting with acute coronary syndromes (ACS). We aimed to compare the clinical outcomes of patients at HBR with chronic coronary syndrome (CCS) or ACS treated with PCI using bioresorbable polymer everolimus-eluting stent (BP-EES) followed by 1-month DAPT. Patients at HBR who underwent PCI with BP-EES were prospectively enrolled in 10 Italian centers. All patients were treated with 1-month DAPT. In case of need for anticoagulation, patients received an oral anticoagulant in addition to a P2Y12 inhibitor for 1 month, followed by oral anticoagulation only after that. The primary end point was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12 months. Overall, 263 patients (59.4%) with CCS and 180 patients (40.6%) with ACS were enrolled. No significant difference was evident between patients with CCS and ACS for the primary end point (4.3% vs 5.6%, respectively, p = 0.497) and for each isolated component. The risk for Bleeding Academic Research Consortium (BARC) type 1 to 5 or type 3 to 5 bleedings was also similar between patients with CCS and ACS (4.3% vs 5.2%, p = 0.677, and 1.6% vs 2.9%, p = 0.351, respectively). In conclusion, among HBR patients with ACS who underwent PCI with BP-EES, a 1-month DAPT strategy is associated with a similar risk of ischemic and bleeding events compared with those with CCS.