[Optical coherence tomography imaging for the evaluation and treatment of calcified coronary artery disease]. / Uso della tomografia a coerenza ottica nella valutazione e nel trattamento della malattia coronarica calcifica.

Coronary calcific disease represents one of the main challenges for the interventional cardiologist, for whom optimal lesion preparation and percutaneous coronary intervention optimization are paramount for correct management. In this perspective, intravascular imaging using optical coherence tomography (OCT) is becoming an increasingly indispensable tool. This work aims to provide a detailed overview of the complexity of calcified lesions, first analyzing their various morphologies and their clinical impact: spotty calcium seems to be more present in plaques at higher risk of destabilization, while diffuse calcification is typical of stable coronary stenosis; the eruptive calcific nodule is one of the three culprit lesion phenotypes responsible for acute coronary syndromes.In the second part of this review, the available technologies for the treatment of calcified lesions are described, with the aid of illustrative OCT images. Intravascular lithotripsy causes fractures at various levels of the calcified plaque, both circumferentially and longitudinally, with an improvement in vessel compliance; atherectomy acts by modifying the composition of the plaque with selective action on the hard calcific component. OCT, providing a comprehensive overview of lesion characteristics, can guide in the selection of the most appropriate therapeutic strategy, while also offering important information on the effectiveness of the chosen treatment.

Acute normovolemic hemodilution in cardiac surgery: rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 ml as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

Anatomical Annulus Predictors of New Permanent Pacemaker Implantation Risk After Balloon-Expandable Transcatheter Aortic Valve Implantation.

New-generation transcatheter heart valves have significantly improved technical success and procedural safety of transcatheter aortic valve implantation (TAVI) procedures; however, the incidence of permanent pacemaker implantation (PPI) remains a concern. This study aimed to assess the role of anatomic annulus features in determining periprocedural conduction disturbances leading to new PPI after TAVI using the last-generation Edwards SAPIEN balloon-expandable valves. In the context of a prospective single-center registry, we integrated the clinical and procedural predictors of PPI with anatomic data derived from multislice computed tomography. A total of 210 consecutive patients treated with balloon-expandable Edwards transcatheter heart valve were included in the study from 2015 to 2023. Technical success was achieved in 197 procedures (93.8%), and 26 patients (12.4%) required new PPI at the 30-day follow-up (median time to implantation 3 days). At the univariable logistic regression analysis, preprocedural right bundle branch block (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.01 to 4.97, p = 0.047), annulus eccentricity ≥0.25 (OR 5.43, 95% CI 2.21 to 13.36, p <0.001), calcium volume at annulus of the right coronary cusp >48 mm3 (OR 2.60, 95% CI 1.13 to 5.96, p = 0.024), and prosthesis implantation depth greater than membranous septum length (OR 2.17, 95% CI 1.10 to 4.28, p = 0.026) were associated with new PPI risk. In the multivariable analysis, preprocedural right bundle branch block (OR 2.81, 95% CI 1.01 to 7.85, p = 0.049), annulus eccentricity ≥0.25 (OR 4.14, 95% CI 1.85 to 9.27, p <0.001), and annulusright coronary cusp calcium >48 mm3 (OR 2.89, 95% CI 1.07 to 7.82, p = 0.037) were confirmed as independent predictors of new PPI. In conclusion, specific anatomic features of the aortic valve annulus might have an additive role in determining the occurrence of conduction disturbances in patients who underwent TAVI with balloon-expandable valves. This suggests the possibility to use multislice computed tomography to improve the prediction of post-TAVI new PPI risk.

A multimodal approach to predict prosthesis-patient mismatch in patients undergoing valve-in-valve trans-catheter aortic valve implantation.

AIMS: The valve-in-valve transcatheter-aortic-valve-implantation (VIV-TAVI) represents an emerging procedure for the treatment of degenerated aortic bio-prostheses, and the occurrence of patient-prosthesis mismatch (PPM) after VIV-TAVI might affect its clinical efficacy. This study aimed to test a multimodal imaging approach to predict PPM risk during the TAVI planning phase and assess its clinical predictivity in VIV-TAVI procedures. METHODS: Consecutive patients undergoing VIV-TAVI procedures at our Institution over 6 years were screened and those treated by self-expandable supra-annular valves were selected. The effective orifice area (EOA) was calculated with a hybrid Gorlin equation combining echocardiographic data with invasive hemodynamic assessment. Severe PPM was defined according to such original multimodality assessment as EOAi≤0.65 cm2/m2 (if BMI < 30 kg/m2) or < 0.55 cm2/m2 (if BMI ≥ 30 kg/m2). The primary endpoint was a composite of all-cause mortality and valve-related re-hospitalization during the clinical follow-up. RESULTS: A total of 40 VIV-TAVI was included in the analysis. According to the pre-specified multimodal imaging modality assessment, 18 patients (45.0 %) had severe PPM. Among all baseline clinical and anatomical characteristics, estimated glomerular filtration rate before VIV-TAVI (OR 0.872, 95%CI[0.765-0.994],p = 0.040), the echocardiographic pre-procedural ≥moderate AR (OR 0.023, 95%CI[0.001-0.964],p = 0.048), the MSCT-derived effective internal area (OR 0.958, 95%CI[0.919-0.999],p = 0.046) and the implantation depth (OR 2.050, 95%CI[1.028-4.086],p = 0.041) resulted as independent predictors of severe PPM at multivariable logistic analysis. At a mean follow-up of 630 days, patients with severe PPM showed a higher incidence of the primary endpoint (9.1%vs.44.4 %;p = 0.023). CONCLUSION: In VIV-TAVI using self-expandable supra-annular valves, a multimodal imaging approach might improve clinical outcome predicting severe PPM occurrence.

Clinical impact of multiple resheathing during transcatheter aortic valve implantation with Evolut self-expanding valves.

BACKGROUND: The possibility to resheath some transcatheter heart valves (THV) facilitates the optimization of self-expandable devices implantation. However, resheating manoeuvres (expecially when repeated) increase the interaction between the transcatheter prosthesis and the patient's tissues potentially causing side-effects. AIMS: To assess the clinical outcomes of resheathing at midterm follow-up with a focus on the safety of multiple resheathing. METHODS: This retrospective observational study included all consecutive patients who underwent TAVI with a self-expandable supra-annular THV between December 2018 and December 2022. Primary endpoint was a composite of cardiovascular (CV) mortality, neurological events, non-fatal acute myocardial infarction and CV rehospitalizations. All clinical endpoints were assessed according to VARC-3 criteria. RESULTS: 469 TAVI procedures with self-expandable supra-annular THV were included in the study. The attempt to resheath and the resheath manoeuvres number was prospectively recorded into an electronic database. Resheating was attempted in 253 (53.9%) cases; 1, 2 and ≥ 3 resheathing were performed in respectively 122 (26.0%), 63 (13.4%) and 68 (14.5%) procedures. At a median follow-up of 640 days (interquartile range 340-1033 days), the incidence of the primary endpoint did not differ between 0 vs. ≥1 (22.7 vs. 26.1%, LogRank p = 0.584) and < 3 vs. ≥3 resheathing groups (24.2 vs. 26.5% LogRank p = 0.963). Furthermore, no significant differences in the primary endpoint were observed between 0, 1-2 and ≥ 3 resheathing (p = 0.84). CONCLUSIONS: Our study found that resheathing of self-expandable THVs during TAVI did not result in worse clinical outcomes compared with no resheathing at mid-term follow-up. These results are independent from the number of resheathing, underling the safety of multiple resheathing in terms of peri-procedural and mid-term outcome. CONDENSED ABSTRACT: In this retrospective observational study of 469 patients undergoing transcatheter aortic valve implantation (TAVI) for symptomatic severe aortic stenosis with self-expanding valves, we investigated the influence of resheathing on mid-term clinical outcomes. Specifically, we focused on the safety of multiple resheathing procedures. Our findings revealed no significant impact of resheathing on medium-term outcomes. The primary endpoint, a composite of cardiovascular mortality, neurological events, non-fatal acute myocardial infarction, and cardiovascular rehospitalizations, did not show statistically significant differences between no resheathing, single resheathing and multiple resheathing groups. Our study suggests that resheathing, even when performed multiple times, does not appear to significantly affect clinical outcomes at mid-term follow-up.

Incidence, Predictors, and Outcomes of Paravalvular Regurgitation after TAVR in Sievers Type-1 Bicuspid Aortic Valves.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve (BAV) stenosis is technically challenging and is burdened by an increased risk of paravalvular regurgitation (PVR). OBJECTIVES: To identify the incidence, predictors, and clinical outcomes of PVR following TAVR in Sievers type 1 BAV stenosis. METHODS: Consecutive patients with severe Sievers type 1 BAV stenosis undergoing TAVR with current generation transcatheter heart valves (THVs) in 24 international centres were enrolled. PVR was graded as none/trace, mild, moderate, and severe according to echocardiographic criteria. The endpoint of major adverse events (MAE), defined as a composite of all-cause death, stroke, or hospitalization for heart failure, was assessed at the last available follow-up. RESULTS: A total of 946 patients were enrolled. PVR occurred in 423 patients (44.7%): mild, moderate, and severe in 387 (40.9%), 32 (3.4%), and 4 (0.4%) patients, respectively. Independent predictors of moderate or severe PVR were larger virtual raphe ring (VRR) perimeter (ORadj 1.07, 95% CI 1.02-1.13), severe annular or left ventricular outflow tract (LVOT) calcification (ORadj 5.21, 95% CI 1.45-18.77), self-expanding valve (ORadj 9.01, 95% CI 2.09-38.86), and intentional supra-annular THV positioning (ORadj 3.31, 95% CI 1.04-10.54). At a median follow-up of 1.3 [IQR 0.5-2.4] years, moderate or severe PVR was associated with an increased risk of MAE (HRadj 2.52, 95% CI 1.24-5.09). CONCLUSIONS: After TAVR with current-generation THVs in Sievers type 1 BAV stenosis, moderate or severe PVR occurred in about 4% of cases and was associated with an increased risk of MAE during follow-up.

Three-Year Clinical Impact of Murray Law-Based Quantitative Flow Ratio and OCT- or FFR-Guidance in Angiographically Intermediate Coronary Lesions.

BACKGROUND: The FORZA trial (FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty) prospectively compared the use of fractional flow reserve (FFR) or optical coherence tomography (OCT) for treatment decisions and percutaneous coronary intervention (PCI) optimization in patients with angiographically intermediate coronary lesions. Murray law-based quantitative-flow-ratio (µQFR) is a novel noninvasive method for the computation of FFR. In the present study, we evaluated the clinical impact of µQFR, FFR, or OCT guidance in FORZA trial lesions at 3-year follow-up. METHODS: µQFR was assessed at baseline and, in the case of a decision to intervene, after (FFR- or OCT-guided) PCI. The baseline µQFR was considered the final µQFR for deferred lesions, and post-PCI µQFR value was taken as final for stented lesions. The primary end point was target vessel failure ([TVF]; cardiac death, target-vessel-related myocardial infarction, and target-vessel-revascularization) at a 3-year follow-up. RESULTS: A total of 419 vessels (199 OCT-guided and 220 FFR-guided) were included in the FORZA trial. µQFR was evaluated in 256 deferred lesions and 159 treated lesions (98 OCT-guided PCI and 61 FFR-guided PCI). In treated lesions, post-PCI µQFR was higher in OCT-group compared with FFR-group (median, 0.93 versus 0.91; P=0.023), and the post-PCI µQFR improvement was greater in FFR-group (0.14 versus 0.08; P<0.0001). At 3-year follow-up, OCT- and FFR-guided treatment decisions resulted in comparable TVF rate (6.7% versus 7.9%; P=0.617). Final µQFR was the only predictor of TVF. µQFR ≤0.89 was associated with 3× increase in TVF (11.6% versus 3.7%; P=0.004). PCI was a predictor of higher final µQFR (odds ratio, 0.22 [95% CI, 0.14-0.34]; P<0.001). CONCLUSIONS: In vessels with angiographically intermediate coronary lesions, OCT-guided PCI resulted in comparable clinical outcomes as FFR-guided PCI. µQFR estimated at the end of diagnostic or interventional procedure predicted 3-year TVF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01824030.

Combined ultrasound and angiographic guidance to facilitate transradial access procedures.

The introduction of transradial access for percutaneous coronary diagnostic and interventional procedures has led to a decrease in access site complications. The aim of this paper is to propose a combined stepwise technical approach where real time ultrasound ("echo-first" approach) can be used to select the best vascular access and, together with angiography, to manage the potential obstacles that may occur during transradial procedures. In each section, we summarize some tips and tricks based on both our experience and current literature that can be easily implemented in daily practice to increase the success of transradial procedures.

Lorcaserin: Worthy of Further Insights? Results from Recent Research.

Lorcaserin is a 3-benzazepine that binds 5-HT2C serotonin receptors in the hypothalamus, where it mediates lack of hunger and/or satiety, and in the ventral tegmental area, the site of origin of the mesolimbic and mesocortical dopaminergic projections, which mediate pleasure and reward. The drug has been first developed for the treatment of obesity, where it has shown efficacy, and subsequently trialed to counter substance use (mostly cocaine, cannabis, opioids, and nicotine) and craving, but showed inconsistent effects. Since 2020, the US Food and Drug Administration obtained that the drug was voluntarily withdrawn from the US market on the grounds that its long-term use was found to be associated with a greater incidence of some types of cancer. Provided it can show to be free from cancerogenic effects, ongoing research suggests that lorcaserin may have therapeutic potential for a variety of disorders and conditions beyond obesity. Since 5-HT2C receptors are involved in many diversified physiological functions (mood, feeding, reproductive behavior, neuronal processes related to impulsiveness, and modulating reward-related mechanisms) this drug has the potential to treat different central nervous system conditions, such as depression and schizophrenia.

Procedural success in transaxillary transcatheter aortic valve implantation according to type of transcatheter heart valve: results from the multicenter TAXI registry.

BACKGROUND: Transaxillary (TAx) transcatheter aortic valve implantation (TAVI) is a preferred alternative access in patients ineligible for transfemoral TAVI. AIMS: This study used the Trans-AXillary Intervention (TAXI) registry to compare procedural success according to different types of transcatheter heart valves (THV). METHODS: For the TAXI registry anonymized data of patients treated with TAx-TAVI were collected from 18 centers. Acute procedural, early and 1-month clinical outcomes were adjudicated in accordance with standardized VARC-3 definitions. RESULTS: From 432 patients, 368 patients (85.3%, SE group) received self-expanding (SE) THV and 64 patients (14.8%, BE group) received balloon-expandable (BE) THV. Imaging revealed lower axillary artery diameters in the SE group (max/min diameter in mm: 8.4/6.6 vs 9.4/6.8 mm; p < 0.001/p = 0.04) but a higher proportion of axillary tortuosity in BE group (62/368, 23.6% vs 26/64, 42.6%; p = 0.004) with steeper aorta-left ventricle (LV) inflow (55° vs 51°; p = 0.002) and left ventricular outflow tract (LVOT)-LV inflow angles (40.0° vs 24.5°; 0.002). TAx-TAVI was more often conducted by right sided axillary artery in the BE group (33/368, 9.0% vs 17/64, 26.6%; p < 0.001). Device success was higher in the SE group (317/368, 86.1% vs 44/64, 68.8%, p = 0.0015). In logistic regression analysis, BE THV were a risk factor for vascular complications and axillary stent implantation. CONCLUSIONS: Both, SE and BE THV can be safely used in TAx-TAVI. However, SE THV were more often used and were associated with a higher rate of device success. While SE THV were associated with lower rates of vascular complications, BE THV were more often used in cases with challenging anatomical circumstances.

Temporal trends of frame expansion and paravalvular leak reduction after transcatheter aortic valve replacement with self-expandable prostheses.

BACKGROUND: Paravalvular leakage (PVL) is a common finding after transcatheter aortic valve replacement (TAVR) and affects late clinical outcome. It is more frequent with self-expandable (SE) transcatheter-heart-valve (THV). Few is known about SE-THV expansion after implantation. The purpose is to assess SE-THV frame expansion and its possible influence on PVL. METHODS: We designed a prospective pilot study to assess the time-course of SE-THV frame dimensions and PVL after TAVR. Consecutive patients undergoing TAVR with SE-THV were enrolled. Prosthesis fluoroscopy and echocardiography were prospectively performed immediately after TAVR (T0) and before discharge (T1) to grade PVL. Prosthesis diameters were assessed in 2 fluoroscopic orthogonal views. PVL reduction ≥1+ from T0 to T1 at echocardiography was the primary study endpoint. RESULTS: Twenty-five patients were enrolled. Mean interval between T0 and T1 evaluations was 5 days. Grade 1 or 2 was present in 76% of patients at T0 and in 68% at T1 (P=0.034). A total of 7 patients (28%) improved PVL ≥1 grade from T0 to T1. Differences between T0 and T1 fluoroscopic diameters were not statistically significant. When comparing the diameter changes according to PVL evolution, patients with PVL improvement (as compared with those without) had significantly larger minimum diameter increase at both annulus/inflow (P=0.016) and outflow/distal edge (P=0.027). CONCLUSIONS: PVL may improve in the early days after SE-THV and those patients with PVL improvement may have THV frame expansion. Further studies are needed to confirm such preliminary observations and to establish the clinical relevance of this phenomenon.

Prognostic value of combined fractional flow reserve and pressure-bounded coronary flow reserve: outcomes in FFR and Pb-CFR assessment.

BACKGROUND: Coronary flow reserve (CFR) has an emerging role to predict outcome in patients with and without flow-limiting stenoses. However, the role of its surrogate pressure bounded-CFR (Pb-CFR) is controversial. We investigated the usefulness of combined use of fractional flow reserve (FFR) and Pb-CFR to predict outcomes. METHODS: This is a sub-study of the PROPHET-FFR Trial, including patients with chronic coronary syndrome and functionally tested coronary lesions. Patients were divided into four groups based on positive or negative FFR (cut-off 0.80) and preserved (lower boundary ≥2) or reduced (upper boundary <2) Pb-CFR: Group1 FFR≤0.80/ Pb-CFR <2; Group 2 FFR≤0.80/Pb-CFR≥2; Group 3 FFR >0.80/Pb-CFR<2; Group 4 FFR>0.80/Pb-CFR≥2. Lesions with positive FFR were treated with PCI. Primary endpoint was the rate of major adverse cardiac events (MACEs), defined as a composite of death from any cause, myocardial infarction, target vessel revascularization, unplanned cardiac hospitalization at 36-months. RESULTS: A total of 609 patients and 816 lesions were available for the analysis. At Kaplan-Meier analysis MACEs rate was significantly different between groups (36.7% Group 1, 27.4% Group 2, 19.2% Group 3, 22.6% Group 4, P=0.019) and more prevalent in groups with FFR≤0.80 irrespective of Pb-CFR. In case of discrepancy, no difference in MACEs were observed between groups stratified by Pb-CFR. FFR≤0.80 was associated with an increased MACEs rate (30.2% vs. 21.5%, P<0.01) while Pb-CFR<2 was not (24.5% vs. 24.2% Pb-CFR≥2 P=0.67). CONCLUSIONS: FFR confirms its ability to predict outcomes in patients with intermediate coronary stenoses. Pb-CFR does not add any relevant prognostic information.

Impact of thrombus aspiration on left ventricular remodeling and function in patients with ST-segment elevation myocardial infarction: A meta-analysis of randomized controlled trials.

BACKGROUND: Routine thrombus aspiration (TA) does not improve clinical outcomes in patients with ST-segment-elevation myocardial infarction (STEMI), although data from meta-analyses suggest that patients with high thrombus burden may benefit from it. The impact of TA on left ventricular (LV) functional recovery and remodeling after STEMI remains controversial. We aimed to pool data from randomized controlled trials (RCTs) on the impact of TA on LV function and remodeling after primary percutaneous coronary intervention (pPCI). METHODS: PubMed and CENTRAL databases were scanned for eligible studies. Primary outcome measures were: LV ejection fraction (LVEF), LV end diastolic volume (LVEDV), LV end systolic volume (LVESV) and wall motion score index (WMSI). A primary pre-specified subgroup analysis was performed comparing manual TA with mechanical TA. RESULTS: A total of 28 studies enrolling 4990 patients were included. WMSI was lower in TA group than in control (mean difference [MD] -0.11, 95% confidence interval [CI] -0.19 to -0.03). A greater LVEF (MD 1.91, 95% CI 0.76 to 3) and a smaller LVESV (MD -6.19, 95% CI -8.7 to -3.6) were observed in manual TA group compared to control. Meta regressions including patients with left anterior descending artery (LAD) involvement showed an association between TA use and the reduction of both LVEDV and LVESV (z = -2.13, p = 0.03; z = -3.7, p < 0.01) and the improvement in myocardial salvage index (z = 2.04, p = 0.04). CONCLUSION: TA is associated with improved LV function. TA technique, total ischemic time and LAD involvement appears to influence TA benefit on post-infarction LV remodeling.