Severe Calcification Research Articles

Atherectomy Techniques: Rotablation, Orbital and Laser

Coronary artery disease remains the leading cause of morbidity and mortality worldwide despite advancements in percutaneous coronary intervention (PCI). With an increasing ageing population, there is a significant challenge in addressing severe calcification in atherosclerotic plaque during angioplasty. This review article focuses on atherectomy strategies such as rotational atherectomy (RA), orbital atherectomy (OA) and excimer laser coronary angioplasty (ELCA) aimed at modifying calcified lesions and improving PCI outcomes. RA modifies plaque through rotational ablation, OA uses eccentrically mounted diamond-coated crown and has a reduced entrapment risk compared to RA. ELCA uses pulsatile laser energy to precisely ablate plaque tissue. This review provides insights into the mechanisms, procedural techniques and clinical outcomes associated with these calcium modification techniques. The selection of appropriate devices and adequate training are crucial for optimising lesion modification and enhancing procedural success. Further research and standardised protocols are required to overcome challenges associated with using these devices and expand their usage in clinical practice.

Assessment of Cutting-Balloon Angioplasty with Novel Bioabsorbable Polymer-Coated Everolimus-Eluting Stent in Treating Calcified Coronary Lesions Guided by Intravascular Ultrasound (CUPID Trial): study design and protocol

BackgroundVarious devices and techniques have been used for plaque modification in the treatment of severe coronary artery calcification. This prospective, multicenter, randomized, open-label study aims to evaluate the safety and efficacy of cutting balloon angioplasty using a novel bioabsorbable polymer-coated everolimus-eluting coronary stent for treating various degrees of calcified coronary lesions.MethodsWe outline the trial design aimed at assessing whether the cutting balloon (Wolverine™) is non-inferior to the non-compliant balloon in treating patients with calcified lesions, encompassing both de novo and in-stent restenosis (ISR) lesions. We aim to enroll 250 patients who have undergone bioabsorbable polymer-coated everolimus-eluting coronary stent (Synergy™) implantation. The primary endpoint is the minimal stent cross-sectional area at the calcium site as determined by intravascular ultrasonography. The secondary endpoints include major adverse cardiac events and target lesion revascularization at 12 months, alongside procedural convenience and operator-centric parameters, such as the number of balloons used, procedure time, and total contrast medium volume used.DiscussionIn this study, we will evaluate the efficacy and safety of Wolverine™ and non-compliant balloon in patients with calcified coronary lesions and provide a rationale for which type of balloons will optimally modify calcium lesions. In addition, we will attempt to expand the indications of the cutting balloon for treating mild-to-severe calcified coronary lesions. As the scope of insurance coverage for cutting balloons remains limited in some countries, this study may provide evidence for extending insurance coverage to the treatment of de novo calcified and ISR lesions.Trial registrationClinicalTrials.gov NCT06177808. Registered on January 1, 2024.

Impact of the distribution of calcification around the left main coronary artery bifurcation on prognosis after percutaneous coronary intervention

Abstract Backgrounds The presence of true bifurcation lesions (TBL) by Medina classification at the left main coronary artery (LMCA) bifurcation is known to be associated with cardiovascular events after percutaneous coronary intervention (PCI). However, the prognostic impact of the distribution of calcification at LMCA bifurcation has not been adequately investigated. Methods This retrospective study consisted of consecutive patients who were implanted with a second or subsequent generation drug-eluting stent for LMCA bifurcation at a single center from 2014 to 2018. We excluded patients with a protected LMCA and those in whom calcification or stenosis of the LMCA bifurcation could not be assessed. With reference to the Medina classification, the region was divided into three segments (LM, LAD, and LCX). Each segment was assigned a value of 0 (for less than moderate calcification) or 1 (for more than moderate calcification) and expressed as calc (X.X.X). Calc (1.1.1), calc (1.0.1), and calc (0.1.1) were defined as true bifurcation calcification (TBC). The primary endpoint was 3-year target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Results Of 498 patients in this analysis, the mean age was 73 years, males accounted for 78% overall, acute coronary syndrome 31% overall, and TBL 42% overall. Moderate or severe calcification at any site around the LMCA bifurcation was observed in 184 (37%). In order of frequency, calc (1.1.0) in 70 (14%), calc (1.1.1) in 58 (12%), calc (0.1.0) in 43 (9%), calc (0.1.1) in 11 (2%), and calc (1.0.1) in 2 (0.4%), while calc (1.0.1) and calc (1. 0.0) were not present. TBC accounted for 14% overall. Patients with TBC at LMCA bifurcation had a higher incidence of 3-year TLF (Log-rank P <0.001; Figure1). Multivariable logistic regression, including age, acute coronary syndrome, maintenance hemodialysis, SYNTAX score ≥33, TBL, and TBC in the model as covariates, TBC was significantly associated with the primary endpoint (adjusted odds ratio 3.4, 95% confidence interval 1.6-7.2, P=0.013). In contrast, a significant association between TBL and the primary endpoint was not observed (adjusted odds ratio 1.5, 95% confidence interval 0.8-2.8, p=0.206). Conclusion Even after adjusting the presence of TBL at LMCA bifurcation, the presence of TBC at LMCA bifurcation was significantly associated with the 3-year TLF.

The acute procedural results and subsequent clinical outcomes after CTO-PCI: main-analysis of the japanese CTO-PCI expert registry

Abstract Background The prospective and nonrandomized registry by Japanese Board of chronic total occlusion (CTO) experts has been finished. The large-scale clinical data related with acute procedural results and subsequent clinical outcomes after CTO-percutaneous coronary intervention (PCI) has received limited study. Objectives The aim of this study was to make clear the procedural results comparing the different primary CTO-PCI approaches and the clinical outcomes after successful CTO-PCI. Methods Between January 2014 and December 2022, a total of 11,674 CTO-PCI patients were consecutively enrolled in this registry. We compared the acute procedural results between 2 groups; primary antegrade approach (PAA) versus primary retrograde approach (PRA), following the intention-to-treat principle. The key outcome of interest was a technical success that was defined as successful stent implantation, residual diameter stenosis <30% within the treated segment, and restoration of TIMI grade 3 flow. The clinical outcomes after achieving technical success of CTO-PCI were assessed in terms of major adverse clinical events (MACE) that were composed of all-cause death, myocardial infarction (MI), and target lesion revascularization (TLR). Moreover, the technical failed factors were also investigated with multivariate analyses. Results Of overall, the technical success rate was 91.9%, but there were significant differences between PAA and PRA groups in terms of the success rate (93.2% vs 88.3%; p < 0.001). The success rates of switching strategy to final antegrade approach after retrograde failure were very low among both groups (PAA; 55.8%, PRA; 68.1%). Of retrograde success group, the successful channel tracking tended to using septal and graft route (70.8% vs 56.0%; p < 0.001). Severe calcification and tortuosity of CTO lesion were stronger predictors of failed CTO-PCI than the other factors of J-CTO score. Also, The median follow-up duration was 446.7±613.4 days. At 1 year, the clinical incidence of MACE was 9.4%. The individual components of MACE were also shown lower rates (All-cause death; 2.6%, MI; 0.8%, TLR; 6.3%). Conclusions In this large cohort of Japanese CTO-PCI registry, CTO-PCI by highly experienced specialists achieved a high technical success rate and clinical impacts. Retrograde approach has been a key to technical success of CTO-PCI in this study.

Association between silent cerebral embolism and cognitive alterations following transcatheter aortic valve replacement in bicuspid versus tricuspid aortic valve patients

Abstract Background Silent cerebral ischemic lesions (SCILs) is a common magnetic resonance imaging (MRI) finding in severe aortic stenosis patients post - transcatheter aortic valve replacement (TAVR). We evaluated the association between SCILs and cognitive alterations in patients with bicuspid aortic valve (BAV) versus tricuspid aortic valve (TAV) post-TAVR. Methods This study enrolled 100 consecutive TAVR (45 with BAV and 55 TAV). DW-MRI and neurocognitive evaluation (MoCA score) were performed at baseline, discharge, and 1- and 12-month post-discharge. Results Ninety-two out of the 100 patients (92%) exhibited cognitive dysfunction at baseline. Post-TAVR, overall cognitive function significantly improved, the average MOCA score increased from 18.69±6.74 to 22.18±6.30. During the 1-year follow-up, 54 patients demonstrated improved cognitive function, and the number of patients with moderate-to-severe cognitive dysfunction (MoCA score < 18) significantly decreased from 32 to 16. Prevalence of SCILs was 14% and 72% at baseline and discharge, respectively. New SCILs were observed in 60 patients at discharge, distributed across all vascular territories, averaging 4 lesions with a total volume of 215.4±195.4mm3. Although no significant correlation existed between total volume of new SCILs and cognitive changes post-TAVR (R=-0.133, p=0.206), patients with SCILs still displayed significant cognitive improvement (MoCA score from 18.4±6.6 to 22.0±7.1), whereas patients who developed large SCILs (lesion diameter >9) showed less improvement compared to those with small or median SCILs (number of patients who had cognitive improvement: 32 vs. 52, p<0.05). Cognitive function improvement post-TAVR did not significantly differ between BAV and TAV patients, MoCA scores were comparable (BAV group, n=45, from 18.63±6.68 to 21.88±6.80 vs. TAV group, n=55, from 18.73±6.81 to 22.42±5.80; p>0.05). DW-MRI revealed more new SCILs in BAV patients post-TAVR compare to TAV patients (235 lesions vs. 150 lesions, respectively). In BAV patients, SCILs primarily manifested in small and medium sizes (224 lesions), despite more severe calcification (valvular calcium volume 956.5±644.0 mm vs. 634.4±508.0 mm3; p=0.028). The number of large lesions was similar in the two groups (11 in BAV group and 10 in TAV group). Conclusion TAVR demonstrates positive effects on improving cognitive function in aortic stenosis patients, despite common occurrence of SCILs in both BAV and TAV patients. Cognitive function post-TAVR was comparable between BAV and TAV patients. The cognitive improvement from TAVR may be less impacted by small- and medium-sized SCILs, while severe SCILs might impede or diminish the cognitive benefits of TAVR.table

Implications of calcified nodule and adjacent calcification severity for target lesion revascularization after percutaneous coronary intervention: multi-center intravascular ultrasound imaging study

Abstract Background Calcified nodule (CN) is a distinct plaque phenotype, characterized as protruding nodular calcification penetrating lumen surface with the attached thrombus. Recent studies revealed that a risk of repeat revascularization after PCI was substantially elevated in patients with coronary artery disease (CAD) attributable to CN. Furthermore, pathohistological studies have elucidated mechanistic insights into the formulation and progression of CN, suggesting that it is formulated by the fracture of sheet calcification at its adjacent segment. Purpose To elucidate the association of calcified plaque volume at CN and adjacent lesions with TLR risks in CAD patients receiving PCI by using IVUS imaging. Methods This multicenter study analyzed IVUS imaging at culprit segment was conducted in 204 CAD patients attributable to de novo CN receiving PCI. The calc grade was assigned at each 1-mm cross-sectional frame of CN and culprit segment, respectively (no calc=0, 1-89°=1, 90-179°=2, 180-269°=3, 270-360°=4). Calcium Volume Index (CVI) at both CN and adjacent zone were calculated (Figure; Calcification volume index at CN zone = the sum of calcium scores at CN・averaged lesion slices of CN / CN lesion slices, Calcification volume index at adjacent zone = the sum of calcium scores at adjacent zone・averaged lesion slices of adjacent zone / adjacent zone slices). Predictors of TLR were analyzed by multivariate Cox hazard model. Results CN was successfully treated by DES (82%) and DCB (18%). 34% and 8.3% of subjects required rotablator and orbital atherectomy, respectively. Consequently, final lumen area after PCI was 7.2 ± 0.4 mm2. During the 2.8-year observational period (interquartile range: 2.4 to 3.2 years), TLR was required in 63 patients (30.9%) of study population. CVI at CN and adjacent zone were 9.9 ± 0.4 and 7.0 ± 0.7, respectively. On multivariate analysis, hemodialysis, final lumen area, CVI at both CN and adjacent zone predicted TLR (Figure). Recurrent TLR (two or more TLRs) was found in 23.3% patients who suffered from TLR. Of note, even among patients who required TLR, CVIs at both zones were significantly higher in patients with recurrent TLR than those without (Figure). Conclusion CAD subjects caused by CN exhibited a considerably high-risk TLRs. Our findings underscore that calcification severity at both CN and adjacent segment predicted TLR and is associated with repeated TLR.methodsResults

Contemporary implantation protocols enable markedly lower pacemaker rate for selfexpandable TAVR

Abstract Background Even in a low-risk cohort, the Evolut low-risk trial has reported a still rather high pacemaker implantation rate over 20%. In the recent years, contemporary implantation protocols have been introduced aiming on a higher implantation position. Purpose Data on a reduction of pacemaker rate in contemporary implantation practice is still limited. Methods We retrospectively analyzed baseline-characteristics and pacemaker-implantation rates after TAVR in patients being treated with a Medtronic Evolut Prosthesis for aortic valve stenosis in our center in the years 2018 (conventional implantation in 3-cusp view) vs. 2023 (contemporary implantation in cusp overlap technique). Results 160 Patients were retrospectively included. We found out, that contemporary implantation lead to a marked reduction of pacemaker rate (8.7 vs. 20.9%, p=0.047; HR 0.36[IQR 0.14-0.96; p=0.041]). While most baseline-parameters including age (83.5 (79.2/87.3) vs. 82.8 (79.4/86.2), p=0.654), LVEF (55.0 (54.3/57.8) vs. 55.0 (51.0/59.0), p=0.992) and overall risk score (Euroscore II 3.5 (2.5/4.7) vs. 3.6 (2.3/5.7), p= 0.726) had no relevant impact on pacemaker rate, female patients were less prone to receive a pacemaker (8.6% vs. 21.3%, p=0.030). Of all conduction disturbances before procedure, a pre-existing RBBB was strongly associated with a relevantly higher pacemaker rate (50.0% vs. 11.3% (p<0.001), HR 7.88 (IQR 2.73/22.74; p<0.001)). Furthermore, more severe leaflet calcification (p=0.049), a deeper implantation depth (6.0 (5.0/6.5) vs. 5.0 (4.0/60.), p=0.042), larger annular dimensions (perimeter 79.7 (75.2/87.7) 76.8 (71.9/80.7), vs. p=0.047) and prostheses sizes (Evolut 34 vs. smaller sizes 28.1 vs. 12.5%, p=0.053), higher BNP (547 (314/1488) vs. 396 (208/856)), p=0.039 and body weight (78.0 (71.3/90.0) vs. 73.0 (63.5/84.5), p=0.030) were attributed to a higher pacemaker rate. Conclusions In our retrospective database we demonstrated that a contemporary implantation protocol enabling higher implantation position leads to a significant reduction in pacemaker rate, even in the high-risk collective of patients with pre-existing RBBB (58.3 vs. 15.2%, p=0.002 compared to 33.3 vs. 6.3%, p=0.081).

Predictors of debulking devices use by coronary artery calcification classification using cardiac CT

Abstract Background Multi-slice computed tomography (CT) is useful for the non-invasive detection and quantification of coronary calcium burden. However, a definitive parameter based on CT imaging for predicting the need for debulking devices, such as rotational atherectomy (RA) and orbital atherectomy (OAS), has yet to be established. Purpose We aimed to develop a calcification risk score using cardiac CT to predict the use of debulking devices during coronary intervention. Methods In this retrospective, multi-center, observational study in Japan, patients who underwent percutaneous coronary intervention (PCI) were screened. Inclusion criteria were (1) cardiac CT within 6 months prior to PCI, (2) moderate or severe coronary calcification detected on CT, and (3) de novo lesions in a native coronary artery. A total of 349 lesions in 343 patients from 13 hospitals, there were 124 lesions that were treated with debulking devices and 225 lesions without debulking devices. Cardiac CT images were analyzed for circumferential degree, longitudinal length, intracoronary distribution of calcification, peak density, mean density, vessel bend and presence of bifurcation lesions. Data from a random two-thirds (the derivation cohort, n=247) were used to develop a new risk prediction model, which was then tested in the remaining one-third (the validation cohort, n=102). Odds ratios and the risk prediction model were developed using a logistic regression model. The predicted risk was translated into a simplified scoring system (Figure 1A). Results RA was used in 111 lesions and OAS in 23 lesions. Factors selected in the model included circumferential degree (≥270°: 3 points), bifurcation (2 points), longitudinal length (≥8mm: 1 point), and mean density (≥600 HU: 1 point) (Figure 1B). This model demonstrated good discrimination (c-statistic=0.772) and calibration (Hosmer–Lemeshow χ²-statistic=0.885; P=0.64) in the validation cohort (Figure 2). Conclusions The new prediction model based on cardiac CT performed well in predicting the need for debulking devices. This could serve as an objective tool to support a clinical decision to use debulking devices even in cases where intravascular imaging is not applicable.Study flow and Cardiac CT calcium scoreDiscrimination and Calibration

Retrograde coronary chronic total occlusion intervention (JR-CTO) score: from the Japanese CTO-PCI expert registry

Abstract Background Despite the effectiveness of the retrograde approach for chronic total occlusion (CTO) lesions, there are no standardized tools to predict the success of retrograde percutaneous coronary intervention (PCI). Purpose The objective of this study was to develop a prediction tool to identify CTO lesions that will achieve successful retrograde PCI. Methods This study evaluated data from 2,374 patients who underwent primary retrograde CTO-PCI and were enrolled in the Japanese CTO-PCI Expert Registry between January 2016 and December 2022. All observations were randomly assigned to the derivation and validation cohorts at a 2:1 ratio. The prediction score for guidewire failure in retrograde CTO-PCI was determined by assigning one point for each factor and summing all accrued points. Results The JR-CTO score (moderate–severe calcification, tortuosity, Werner collateral connection grade ≤ 1, and non-septal collateral channel) demonstrated a c statistic for guidewire failure of 0.72 (95% confidence interval: 0.67–0.76) and 0.71 (95% confidence interval: 0.64–0.77) in the derivation and validation cohorts, respectively. Patients with lower scores had higher guidewire and technical success rates and decreased guidewire crossing time and procedural time (P < 0.01). Conclusions The JR-CTO score, a simple four-item score that predicts successful guidewire crossing in patients undergoing retrograde CTO-PCI, has the potential to support clinical decision-making for the retrograde approach.

Impact of the lower extremity arterial calcification score on clinical outcomes after drug-coated balloon angioplasty for de novo femoropopliteal artery disease

Abstract Background Severe calcification, assessed using the peripheral artery calcification scoring system (PACCS), is associated with poor clinical outcomes after endovascular treatment (EVT) for de novo femoropopliteal lesions. However, the PACCS classification is a qualitative assessment performed in the angiographic room, and there are no established indicators for the quantitative assessment of calcification prior to treatment. Purpose We aimed to investigate the impact of the lower extremity arterial calcification score (LEACS) calculated using non-contrast lower limb computed tomography on clinical outcomes after drug-coated balloon angioplasty for de novo femoropopliteal artery disease. Methods We retrospectively analyzed the clinical outcomes of 141 consecutive patients treated at our center for de novo femoropopliteal artery disease using a drug-coated balloon between April 2018 and December 2022. Patients who did not undergo lower limb computed tomography before EVT were excluded from the analyses. LEACS was determined based on the method used to calculate the Agatston score for the coronary arteries. Each patient’s score consisted of a sum of calcification scores from ostium of superficial artery to the popliteal artery at the knee joint of treated limb. The primary and secondary outcomes measured were primary patency and clinically-driven target vessel revascularization (CD-TVR) at 1 year. Cox proportional hazards analysis was used to explore independent predictors of clinical outcomes. The study population was divided into higher and lower LEACS groups based on the cut-off value (1750), which best discriminated patency, and the outcomes were compared between the two groups. Results In the higher and lower LEACS groups, the mean age was 75.1 ± 9.1 years and 75.5 ± 11.0 years (p = 0.87) and the mean lesion length was 170.3±102.8 mm and 157.7±112.1 mm (p = 0.64), respectively. The higher LEACS group showed significantly lower 1-year patency than the lower LEACS group (53.5% vs. 84.3%, log-rank, p = 0.041). In addition, freedom from 1-year CD-TVR was significantly lower in the higher LEACS group than in the lower LEACS group (66.8% vs. 93.7%, p = 0.047). The Cox proportional hazard analysis showed that the higher LEACS group was an independent predictor of 1-year restenosis (odds ratio: 2.80, 95% confidence interval: 1.24–8.84, p=0.037), along with a small (< 5 mm) reference vessel diameter (odds ratio: 3.55, 95% confidence interval: 1.44–9.53, p=0.028). Conclusion Higher LEACS scores were independently associated with clinical outcomes after drug-coated balloon angioplasty for de novo femoropopliteal artery disease. Non-contrast lower limb computed tomography is an acceptable and feasible option for predicting the outcomes in patients with de novo femoropopliteal artery disease prior to treatment.

Imaging characteristics and clinical outcomes of hemodialysis vs. non-hemodialysis patients undergoing transcatheter aortic valve replacement: a Japanese single-center experience.

In 2021, Japan approved transcatheter aortic valve replacement (TAVR) for end-stage renal disease patients on hemodialysis (ESRD-HD). Yet, clinical/anatomical differences and outcomes between patients with and without ESRD-HD remain underexplored. This single-center study enrolled consecutive patients who underwent TAVR with the SAPIEN 3 between 2021 and 2023. Baseline characteristics and outcomes up to 1year were compared. Inverse probability treatment weighting (IPTW) approach and Cox regression were used. Among 287 eligible patients, 59 had ESRD-HD. Patients with ESRD-HD were predominantly male (59.2% vs. 40.7%; p = 0.01), younger (78.0 [73.5-83.5] vs. 84.0 [79.8-88.0]; < 0.001), with lower body mass index (21.4 [19.6-23.3] vs. 22.9 [20.3-25.3]; p = 0.02], higher surgical risk (Society of Thoracic Surgeons Predicted Risk of Mortality ≧8%: 28 [47.5%] vs. 34 [14.9%]; p < 0.001), and more peripheral artery disease (25.4% vs. 4.8%; p < 0.001). Patients with ESRD-HD had a significantly higher prevalence of severely calcified femoral arteries (12.5% vs. 2.6%; p < 0.001). However, there were no differences in the computed-tomographic (CT) anatomical characteristics of the aortic valve complex (AVC), including the aortic valve calcium score (1995 [1372-3374] vs. 2195 [1380-3172]; p = 0.65) or the presence of moderate or severe left ventricular outflow tract calcification (4.3% vs. 5.2%; p > 0.99). Major vascular complications were rare, and technical (98.3% vs. 98.7%; p > 0.99) and device success (75.9% vs. 82.4%; p = 0.26) rates were high in both. At 1year, there were no significant differences in a composite endpoint of death, stroke, major bleeding, or myocardial infarction (32.4% vs. 33.2%; HR 1.12; 95% CI 0.45-2.80; p = 0.81), nor its components after baseline adjustment.

Predictors and Clinical Outcomes of True Mitral Stenosis in Patients Undergoing Transcatheter Aortic Valve Implantation

Abstract Aims Predictors of true degenerative mitral stenosis (MS) in patients with aortic stenosis who underwent transcatheter aortic valve implantation (TAVI) remain unknown. This study aimed to investigate the predictors and prognostic value of true degenerative MS in this population. Methods and results We retrospectively reviewed the records of 760 consecutive patients who underwent TAVI. The mitral valve area (MVA) was assessed using transthoracic echocardiography, and mitral valve calcification was assessed using multi-detector computed tomography. MS was defined as an MVA of ≤2.0 cm², and true MS was defined as moderate or severe MS following TAVI. In our TAVI cohort, we identified 72 (9.5%) patients with degenerative MS. Among these, true MS was observed in 38 (52.7%) patients. Echocardiographic data showed that the true MS group had a significantly lower MVA and higher trans-mitral gradient. The severity of mitral annular calcification was not significantly different between the two groups; however, the true MS group had significantly more posterior mitral leaflet (PML) and anterior mitral leaflet (AML) calcification. Multivariable logistic regression analysis showed that AML calcification was the independent predictor of true MS (adjusted OR, 9.23; 95% CI 2.84‒29.9). True MS was independently associated with poor prognosis (adjusted HR, 2.76; 95% CI 1.09‒6.98). Conclusions Approximately half of patients with concomitant degenerative MS who underwent TAVI had true MS, which was associated with a poor prognosis. Computed tomographic analysis of AML calcification was useful for predicting true MS.

Exploring the Association of Smoking and Alcohol Consumption with Presence of and Severe Coronary Artery Calcification.

Despite the majority of studies have identified smoking as a risk factor for coronary artery calcification (CAC), some studies have not identified this relationship. Differences on results reached by studies on the association of alcohol consumption with CAC exist. Moreover, studies have almost exclusively investigated the association between smoking and alcohol consumption independently. Whether an interaction effect of alcohol on the association of smoking and CAC exists has hardly been investigated. The data of 2431 adult patients who visited Fuwai Hospital, Chinese Academy of Medical Sciences from September, 2001 to December, 2023 and had Agaston coronary artery calcification score (CACS) reported were utilized. Patients who (1) underwent percutaneous coronary intervention, coronary bypass graft and heart transplantation, or (2) were complicated by acute medical conditions, chronic kidney disease or malignant neoplasms were excluded. Data from 1528 patients were eventually analyzed. Logistic regression was employed to investigate the association of smoking and alcohol consumption with presence of CAC and severe CAC. Interaction effects of alcohol consumption history on the association of current smoking and both presence of and severe CAC were examined. Smoking history was significantly associated with presence of CAC and severe CAC. Current alcohol consumption was also significantly associated with presence of CAC and severe CAC. After adjusting for confounders, alcohol consumption history demonstrated an interaction effect on the association of current smoking with both presence of and severe CAC. Using non-alcohol consumers not smoking at the time of the study as reference, current smokers with an alcohol consumption history suffered from an increased risk of presence of CAC and severe CAC. Both smoking history and current alcohol consumption were associated with presence of and severe CAC. Alcohol consumption history demonstrated an interaction effect on the association of current smoking with both presence of and severe CAC.

Success Rate of Drilling and Knuckle Wire Crossing Technique in Chronic total Occlusion of the Femoro-Popliteal Artery and Predicting Factors Related to it in Real-World Data

Objective: Crossing chronic total occlusion (CTO) in femoro-popliteal (FP) arteries is challenging. Hence, this study aimed to describe real-world data on the technical success rate of crossing FP CTO lesions, and analyze predicting factors for crossing failure. Material and Methods: This retrospective study, conducted at a single center, involved patients with peripheral arterial disease (PAD) and FP CTOs, categorized as Rutherford categories 3-6, having undergone endovascular recanalization from 2017 to 2022. Baseline characteristics and crossing success rates were described using frequencies, percentages, means, medians, standard deviations, and interquartile ranges. Factors associated with crossing failure were analyzed through logistic regression analysis, with statistical significance set at a p-value&lt;0.05.Results: Among the 181 patients analyzed, the majority exhibited minor tissue loss (63%) and severe disease (TASC II category D, GLASS grade 4). The predominant CTO crossing approach was based on plaque cap morphology (CTOP) classification type B (66.9%), with severe CTO calcification (PACSS type 4) in 23.8%. Median occlusion length was 16.1 cm; 85.6% successfully crossed the CTO and antegrade success was 57.5%. Factors associated with crossing failure included: CTOP types C or D, CTO at the P3-popliteal artery, severe CTO calcification, and dyslipidemia. Retrograde recanalization showed higher success rates in CTOP type D and longer occlusions.Conclusion: This study highlights the safety and effectiveness of the catheter-wire crossing technique for FP CTOs. CTOP classification, CTO location, severe calcification, and dyslipidemia predicted crossing failure. The retrograde approach works well in CTOP type D and longer CTOs, providing insights for improving success in clinical practice.

Visceral Obesity and Its Association with Severe Coronary Artery Calcification in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background/Objectives: The role of body composition parameters in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with presence and severity of coronary artery calcification (CAC) is still not fully elucidated. We aimed to evaluate the impact of computed tomography (CT)-based body composition parameters in patients with MASLD with CAC severity. Methods: In this multicenter study, 1870 individuals underwent cardiac CT for the detection of CAC as well as ultrasonography for the diagnosis of hepatic steatosis. The presence of CAC was defined by a CAC score threshold of >0, while severe CAC was defined by a threshold of >300. Using the abdominal cross-sectional CT images at the L3 vertebra level, we analyzed the skeletal muscle index, visceral to subcutaneous adipose tissue ratio, and muscle density using the Hounsfield unit. Results: Of 648 patients with MASLD, the proportions of presence of CAC and severe CAC were 45.2% and 9.9%, respectively. Visceral obesity was not associated with the presence of CAC after adjustment for age, sex, smoking, statin therapy, type 2 diabetes, and advanced fibrosis (adjusted odds ratio (aOR), 1.38; 95% confidence interval (CI), 0.86-2.23; p = 0.180). However, visceral obesity was independently associated with severe CAC after adjustment for several metabolic risk factors (aOR, 3.54; 95% CI, 1.25-14.90; p = 0.039), and adjustment for atherosclerotic cardiovascular disease risk scores (aOR, 3.74; 95% CI, 1.31-15.79; p = 0.032). Conclusions: Visceral obesity may serve as a novel prognostic CT-based radiological biomarker for patients with MASLD with severe CAC.

Impact of Pelvic Calcification Severity on Renal Transplant Outcomes: A Prospective Single-Center Study.

Background: Vascular calcifications (VC) are increasingly prevalent in patients with chronic kidney disease. This study aimed to assess the incidence of iliac artery calcifications in kidney transplant (KT) patients and explore the relationship between iliac VC burden measured by pelvic calcification score (PCS) and renal transplant outcomes. Methods: This prospective study involved 79 KT recipients. VC quantification, using a pre-transplant computed tomography (CT) scan, was performed by assessing calcifications in the common and external iliac arteries bilaterally, resulting in an overall PCS ranging from 0 (no calcifications) to 44 (extensive calcifications). Based on PCS values, patients were divided into three equal-sized groups: PCS Group 1 (PCS 0-4), PCS Group 2 (PCS 5-19), and PCS Group 3 (PCS > 19). Post-transplant outcomes tracked for at least 1 year were patient and graft survival, graft function (urea, creatinine, MAG-3 clearance), and incidence of MACE during the first post-transplant year. Results: Calcifications were present in at least one arterial segment in 61 patients (77.2%). One-year patient survival was 95%, and one-year graft survival was 92.4%. Patients in PCS Group 3 had significantly lower one-year patient and graft survival compared to those in PCS Group 1 and 2 (p = 0.006 and p = 0.008, respectively). MACE and renal function indicators 1-year post-transplant were similar across all PCS groups. Conclusions: Our study demonstrated that a significant majority of KT recipients exhibited iliac VC during pre-transplant CT assessments. Patients in PCS Group 3 exhibited significantly lower one-year patient and graft survival rates compared to those in PCS Groups 1 and 2, indicating that this subgroup may require more intensive post-transplant monitoring and management.

Effectiveness of Intravascular Lithotripsy on an Underexpanded Stent Due to Severe Calcification.

Effectiveness of Intravascular Lithotripsy on an Underexpanded Stent Due to Severe Calcification.

Totally 3D endoscopic aortic valve replacement: initial results and experience from a single center.

This study aimed to evaluate the feasibility and initial outcomes of totally endoscopic aortic valve replacement (TEAVR) performed via a single working port at the fourth intercostal space (ICS) utilizing a 3D endoscopic system. A retrospective observational study was conducted on 35 consecutive patients who underwent TEAVR over a six-month period from December 2023 to June 2024. Patient selection was based on the presence of isolated aortic valve disease without the need for ascending aorta replacement or aortic root enlargement. A 4 cm single working port was created at the 4th ICS, extending from the right mid-axillary to the anterior axillary line. A 10-mm trocar for a 3D endoscope was placed at the right anterior-axillary line. Peripheral cardiopulmonary bypass (CPB) was established. The primary outcomes investigated included the success rate of the procedure, in-hospital mortality, and perioperative complications. The mean age of the patients was 58.7 ± 12.8 years, with 22.9% being female. The majority of patients (77.1%) presented with aortic stenosis, often accompanied by severe calcification. The medianCPB time was 210 ± 43 min, and the median aortic cross-clamp time was 132 ± 41 min. The procedure was successfully completed in all patients using the endoscopic approach, with no conversions to full sternotomy. Two mortalities were recorded, attributed to postoperative complications including bleeding and cerebral infarctions. The early (30-day) mortality rate was 5.7%. Prolonged mechanical ventilation (>48 h) was required in 17.1% of patients, and reoperation for bleeding was necessary in 2.9% of patients. TEAVR is a feasible procedure with the potential to replace the traditional sternotomy approach for aortic valve replacement.

7217 Impact of INZ-701 on Bone and Mineral Metabolism Biomarkers and Clinical Outcomes in Adults with ENPP1 Deficiency - Results from 48-week Phase 1/2 Open Label Study

Abstract Disclosure: K. Gunter: Employee; Self; Inozyme Pharma. Stock Owner; Self; Inozyme Pharma. R.A. Wermers: Research Investigator; Self; Inozyme Pharma. R. Fuhr: Employee; Self; Parexel GmbH. Research Investigator; Self; Inozyme Pharma. D. Schnabel: Research Investigator; Self; Inozyme Pharma. A. Besancon: Research Investigator; Self; Inozyme Pharma. M.A. Nour: Research Investigator; Self; Inozyme Pharma. D. Wenkert: Stock Owner; Self; Inozyme Pharma. Y. Sabbagh: Employee; Self; Inozyme Pharma. Stock Owner; Self; Inozyme Pharma. Background: ENPP1 Deficiency is a rare disorder due to inactivating mutations in the ENPP1 gene that result in low levels of inorganic pyrophosphate (PPi), a critical regulator of mineralization. Subsequent pathologic soft tissue calcification results in severe vascular calcification and ∼50% infant mortality. By early adolescence the majority of survivors develop FGF-23 mediated hypophosphatemic rickets, characterized by bone deformities, short stature, joint/ligament calcification and musculoskeletal pain. No targeted therapy exists for this disease. INZ-701 is a recombinant ENPP1-Fc investigational product. Purpose: To describe the safety, tolerability, immunogenicity, and exploratory efficacy (bone and mineral metabolism biomarkers and clinical outcomes) of INZ-701 in adults with ENPP1 Deficiency through the end of the phase 2 study period (week 48). Methods: Phase 1/2, multicenter, open-label, multiple ascending dose study including three adults in each of three dose cohorts (0.2, 0.6 and 1.8 mg/kg, total N=9) with genetic variants in ENPP1 and PPi &amp;lt;1300 nM (NCT04686175). Participants were dosed subcutaneously on Day 1, then twice weekly from Day 8 to end of study. Data through wk 48 as of July 6, 2023 are included; topline wk 48 data will be presented. Per protocol, participants may continue to receive INZ-701 beyond wk 48. Results: Rapid increase in mean PPi from baseline of 426±407 nM was noted in all patients, reaching the healthy volunteer range within 6 hrs of the first dose with sustained elevation through wk 48. Mean PPi across the 0.2, 0.6 and 1.8 mg/kg dose cohorts from day 32 to wk 48 was 1299±131 nM, 1356±136 nM, and 1282±81 nM, respectively. There were improvements from baseline to wk 48 in mean pooled FGF-23 (-22 pg/mL) and serum phosphate (+0.18 mg/dL), with dose-dependent changes in bone specific alkaline phosphatase consistent with bone healing. DEXA revealed improvements in spine BMD and BMC. There were trends towards improvement in mean % predicted change in 6MWT from baseline to wk 48: cohort 1, 76.7% (SE 10.5) to 85.0% (SE 3.0); cohort 2, 52.2% (SE 10.9 ) to 79.0% (SE 2.9); cohort 3, wk 48 data not available. Improvements were also observed in physician and patient global impression of change score (with no patients deteriorating) and PROMIS pain intensity score. INZ-701 was well tolerated with no drug-related serious or severe (&amp;gt; grade 2) adverse events. Low titers of non-neutralizing anti-drug antibodies (≤160) were observed in 7/9 patients. Long half-life of approximately 126 hours suggests the potential for once-weekly dosing. Conclusions: In adults with ENPP1 Deficiency, INZ-701 was well tolerated with no related serious or severe adverse events. INZ-701 demonstrated a rapid and sustained increase in PPi levels from baseline to week 48 with corresponding improvements in bone mineral biomarkers, functional performance, and patient and physician-reported outcomes. Presentation: 6/3/2024

Endo-Aortic Clamping with the IntraClude® Device in Minimally Invasive Total Coronary Revascularization via Left Anterior Thoracotomy (TCRAT)

Minimally invasive, sternum-sparing total coronary revascularization in multivessel disease via left anterior mini-thoracotomy (TCRAT) was introduced recently. Intra-aortic balloon occlusion is a conceivable option to avoid manipulation of the ascending aorta, to reduce the risk of stroke and to be able to treat patients with severe calcifications and unfavorable aortic anatomies. Background/Objectives: The aim of our study was to show that the use of the IntraClude® device, as part of minimally invasive coronary artery bypass grafting (CABG) via left anterior mini-thoracotomy, is feasible. Methods: From May to December 2023, CABG via left anterior mini-thoracotomy on cardiopulmonary bypass and cardioplegic arrest was successfully performed in 20 patients (17 male, 67.6 ± 8.2 (51–82) years). All patients had significant coronary artery disease (three-vessel: n = 6; two-vessel: n = 11; one-vessel: n = 3) with indication for surgical revascularization. The mean EuroScore2 was 2.6. Results: All patients successfully underwent minimally invasive CABG using endo-aortic balloon occlusion. A total of 43 distal anastomoses (2.2 ± 0.6 (1–3) per patient) were performed by using left internal artery mammary (n = 20) and radial artery (n = 14) for grafting the left anterior descending (n = 19), circumflex (n = 15) and right (n = 6) coronary artery. There was no hospital mortality, no stroke, no myocardial infarction or repeat revascularization. A total of 15 out of 20 patients left hospital within 8 days after surgery. Conclusions: TCRAT by using the IntraClude® device is feasible without compromising surgical principles while avoiding the external manipulation of the ascending aorta. The use of intra-aortic balloon occlusion instead of transthoracic clamps further reduces the invasiveness of the procedure.