Prevalence and risk factors for Q fever, spotted fever group rickettsioses, and typhus group rickettsioses in a pastoralist community of northern Tanzania, 2016-2017.

BACKGROUND: In northern Tanzania, Q fever, spotted fever group (SFG) rickettsioses, and typhus group (TG) rickettsioses are common causes of febrile illness. We sought to describe the prevalence and risk factors for these zoonoses in a pastoralist community. METHODS: Febrile patients ≥2 years old presenting to Endulen Hospital in the Ngorongoro Conservation Area were enrolled from August 2016 through October 2017. Acute and convalescent blood samples were collected, and a questionnaire was administered. Sera were tested by immunofluorescent antibody (IFA) IgG assays using Coxiella burnetii (Phase II), Rickettsia africae, and Rickettsia typhi antigens. Serologic evidence of exposure was defined by an IFA titre ≥1:64; probable cases by an acute IFA titre ≥1:128; and confirmed cases by a ≥4-fold rise in titre between samples. Risk factors for exposure and acute case status were evaluated. RESULTS: Of 228 participants, 99 (43.4%) were male and the median (interquartile range) age was 27 (16-41) years. Among these, 117 (51.3%) had C. burnetii exposure, 74 (32.5%) had probable Q fever, 176 (77.2%) had SFG Rickettsia exposure, 134 (58.8%) had probable SFG rickettsioses, 11 (4.8%) had TG Rickettsia exposure, and 4 (1.8%) had probable TG rickettsioses. Of 146 participants with paired sera, 1 (0.5%) had confirmed Q fever, 8 (5.5%) had confirmed SFG rickettsioses, and none had confirmed TG rickettsioses. Livestock slaughter was associated with acute Q fever (adjusted odds ratio [OR] 2.54, 95% confidence interval [CI] 1.38-4.76) and sheep slaughter with SFG rickettsioses case (OR 4.63, 95% CI 1.08-23.50). DISCUSSION: Acute Q fever and SFG rickettsioses were detected in participants with febrile illness. Exposures to C. burnetii and to SFG Rickettsia were highly prevalent, and interactions with livestock were associated with increased odds of illness with both pathogens. Further characterisation of the burden and risks for these diseases is warranted.

Technical aspects of entrapped coronary guidewire retrieval using rotational atherectomy device: A case series.

BACKGROUND: This article highlights four unique cases where rotational atherectomy (RA Rotapro, Boston Scientific) was used to cut and retrieve an entrapped coronary guidewire with parts extending into the aorta We discuss the technique and step by step approach to the retrieval procedure. CASE SUMMARY: Three of four cases described a guide wire entrapment in the right coronary artery (RCA), and one in the left anterior descending artery via retrograde route. In all cases the guide wire was intact within the intracoronary segment. In Case 1, the guide wire (Runthrough; Terumo) was entrapped in an acute marginal branch during chronic total occlusion (CTO) percutaneous coronary intervention. In Case 2, a whisper wire (Abbott) was entrapped during re-wiring of the right posterolateral branch through stent struts, the traction on the wire caused severe malformation of distal and proximal stents requiring second staged procedure to complete revascularization of the RCA CTO. In Case 3, a Runthrough wire was entrapped between two layers of stents and fractured at the proximal point with filaments extending into descending aorta. And in Case 4, a Pilot 200 (Abbott) wire was entrapped retrograde in the subintimal space via saphenous vein graft connection by tying a knot at the distal tip of the wire. In all four cases RA was used to successfully cut and remove the entrapped guide wires. DISCUSSION: Rotablation technique appears to be a safe and effective strategy for the management of entrapped coronary guidewire when conventional strategies fail.

International survey of chronic total occlusion percutaneous coronary intervention operators.

BACKGROUND: Contemporary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) practice has received limited study. AIM: To examine the contemporary CTO PCI practice. METHODS: We performed an online, anonymous, international survey of CTO PCI operators. RESULTS: Five hundred forty-five CTO PCI operators and 190 interventional cardiology fellows with an interest in CTO PCI participated in this survey. Almost half were from the United States (41%), most (93%) were men, and the median h/week spent in the hospital was 58. Median annual case numbers were 205 (150-328) for PCIs and 20 (5-50) for CTO PCIs. Almost one-fifth (17%) entered CTO cases into registries, such as PROGRESS-CTO (55%) and EuroCTO (20%). More than one-third worked at academic institutions (39%), 31% trained dedicated CTO fellows, and 22% proctored CTO PCI. One-third (34%) had dedicated CTO PCI days. Most (51%) never discharged CTO patients the same day, while 17% discharged CTO patients the same day >50% of the time. After successful guidewire crossing, 38% used intravascular imaging >90% of the time. Most used CTO scores including J-CTO (81%), PROGRESS-CTO (35%), and PROGRESS-CTO complications scores (30%). Coronary artery perforation was encountered within the last month by 19%. On a scale of 0-10, the median comfort levels in treating coronary artery perforation were: covered stents 8.8 (7.0-10), coil embolization 5.0 (2.1-8.5), and fat embolization 3.7 (0.6-7.3). Most (51%) participants had a complication cart/kit and 25% conducted regular complication drills with catheterization laboratory staff. CONCLUSION: Contemporary CTO PCI practices vary widely. Further research on barriers to following the guiding principles of CTO PCI may improve patient outcomes.

Retrograde chronic total occlusion percutaneous coronary intervention via ipsilateral collaterals.

BACKGROUND: There is limited data on retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) via ipsilateral epicardial collaterals (IEC). AIMS: To compare the clinical and angiographic characteristics, and outcomes of retrograde CTO PCI via IEC versus other collaterals in a large multicenter registry. METHODS: Observational cohort study from the Prospective Global registry for the study of Chronic Total Occlusion Intervention (PROGRESS-CTO). RESULTS: Of 4466 retrograde cases performed between 2012 and 2023, crossing through IEC was attempted in 191 (4.3%) cases with 50% wiring success. The most common target vessel in the IEC group was the left circumflex (50%), in comparison to other retrograde cases, where the right coronary artery was most common (70%). The Japanese CTO score was similar between the two groups (3.13 ± 1.23 vs. 3.06 ± 1.06, p = 0.456); however, the IEC group had a higher Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) score (1.95 ± 1.02 vs. 1.27 ± 0.92, p < 0.0001). The most used IEC guidewire was the SUOH 03 (39%), and the most frequently used microcatheter was the Caravel (43%). Dual injection was less common in IEC cases (66% vs. 89%, p < 0.0001). Technical (76% vs. 79%, p = 0.317) and procedural success rates (74% vs. 79%, p = 0.281) were not different between the two groups. However, IEC cases had a higher procedural complications rate (25.8% vs. 16.4%, p = 0.0008), including perforations (17.3% vs. 9.0%, p = 0.0001), pericardiocentesis (3.1% vs. 1.2%, p = 0.018), and dissection/thrombus of the donor vessel (3.7% vs. 1.2%, p = 0.002). CONCLUSION: The use of IEC for retrograde CTO PCI was associated with similar technical and procedural success rates when compared with other retrograde cases, but higher incidence of periprocedural complications.

Paclitaxel-Coated Balloon vs Uncoated Balloon for Coronary In-Stent Restenosis: The AGENT IDE Randomized Clinical Trial.

Importance: Drug-coated balloons offer a potentially beneficial treatment strategy for the management of coronary in-stent restenosis. However, none have been previously evaluated or approved for use in coronary circulation in the United States. Objective: To evaluate whether a paclitaxel-coated balloon is superior to an uncoated balloon in patients with in-stent restenosis undergoing percutaneous coronary intervention. Design, Setting, and Participants: AGENT IDE, a multicenter randomized clinical trial, enrolled 600 patients with in-stent restenosis (lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm) at 40 centers across the United States between May 2021 and August 2022. One-year clinical follow-up was completed on October 2, 2023. Interventions: Participants were randomized in a 2:1 allocation to undergo treatment with a paclitaxel-coated (n = 406) or an uncoated (n = 194) balloon. Main Outcomes and Measures: The primary end point of 1-year target lesion failure-defined as the composite of ischemia-driven target lesion revascularization, target vessel-related myocardial infarction, or cardiac death-was tested for superiority. Results: Among 600 randomized patients (mean age, 68 years; 157 females [26.2%]; 42 Black [7%], 35 Hispanic [6%] individuals), 574 (95.7%) completed 1-year follow-up. The primary end point at 1 year occurred in 17.9% in the paclitaxel-coated balloon group vs 28.6% in the uncoated balloon group, meeting the criteria for superiority (hazard ratio [HR], 0.59 [95% CI, 0.42-0.84]; 2-sided P = .003). Target lesion revascularization (13.0% vs 24.7%; HR, 0.50 [95% CI, 0.34-0.74]; P = .001) and target vessel-related myocardial infarction (5.8% vs 11.1%; HR, 0.51 [95% CI, 0.28-0.92]; P = .02) occurred less frequently among patients treated with paclitaxel-coated balloon. The rate of cardiac death was 2.9% vs 1.6% (HR, 1.75 [95% CI, 0.49-6.28]; P = .38) in the coated vs uncoated balloon groups, respectively. Conclusions and Relevance: Among patients undergoing coronary angioplasty for in-stent restenosis, a paclitaxel-coated balloon was superior to an uncoated balloon with respect to the composite end point of target lesion failure. Paclitaxel-coated balloons are an effective treatment option for patients with coronary in-stent restenosis. Trial Registration: ClinicalTrials.gov Identifier: NCT04647253.

Validation of the new PROGRESS-CTO complication risk scores in the OPEN-CTO registry.

BACKGROUND: Risk stratification before chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is important to inform procedural planning as well as patients and their families. We sought to externally validate the PROGRESS-CTO complication risk scores in the OPEN-CTO registry. METHODS: OPEN-CTO is a prospective registry of 1000 consecutive CTO PCIs performed at 12 experienced US centers using the hybrid algorithm. Endpoints of interest were in-hospital all-cause mortality, need for pericardiocentesis, acute myocardial infarction (MI), and major adverse cardiovascular events (MACE) (a composite of all-cause mortality, stroke, periprocedural MI, urgent repeat revascularization, and tamponade requiring pericardiocentesis). Model discrimination was assessed with the area under the curve (AUC) method, and calibration with the observed-versus-predicted probability method. RESULTS: Mean age was 65.4 ± 10.3 year, and 36.5% of patients had prior coronary artery bypass graft. Overall, 41 patients (4.1%) suffered MACE, 9 (0.9%) mortality, 26 (2.6%) acute MI, and 11 (1.1%) required pericardiocentesis. Technical success was achieved in 86.3%. Patients who experienced MACE had higher anatomic complexity, and more often required antegrade dissection/reentry and the retrograde approach. Increasing PROGRESS-CTO MACE scores were associated with increasing MACE rates: 0.5% (score 0-1), 2.4% (score 2), 3.7% (score 3), 4.5% (score 4), 7.8% (score 5), 13.0% (score 6-7). The AUC were as follows: MACE 0.72 (95% confidence interval [CI]: 0.66-0.78), mortality 0.79 (95% CI: 0.66-0.95), pericardiocentesis 0.71 (95% CI: 0.60-0.82), and acute MI 0.57 (95% CI: 0.49-0.66). Calibration was adequate for MACE and mortality, while the models underestimated the risk of pericardiocentesis and acute MI. CONCLUSIONS: In a large external cohort of patients treated with the hybrid algorithm by experienced CTO operators, the PROGRESS-CTO MACE, mortality, and pericardiocentesis risk scores showed good discrimination, while the acute MI score had inferior performance.

Intravascular lithotripsy compared to rotational atherectomy for the treatment of calcified distal left main coronary artery disease: A single center experience.

BACKGROUND: The safety and efficacy of intravascular lithotripsy (IVL) for the treatment of calcified distal left main (LM) disease remains unclear, especially compared to rotational atherectomy (RA). METHODS: We retrospectively analyzed the baseline clinical, angiographic, intravascular ultrasound (IVUS) characteristics and procedural outcomes of 107 patients who underwent distal LM percutaneous coronary intervention (PCI) with IVL (with or without adjunct atherectomy) versus RA alone for plaque modification before stenting at a single center between 2020 and 2022. RESULTS: A total of 50 patients underwent calcium modification with IVL with or without adjunct atherectomy and 57 with RA only. The mean age was 73 years and with a high prevalence of diabetes (58.9%), chronic kidney disease (42.1%), prior revascularization (coronary artery bypass graft surgery [36.4%] or prior PCI [32.7%]). Acute coronary syndrome was the primary indication for PCI in over 50% of the patients in both groups. Medina 1-1-1 LM bifurcation disease was identified in 64% and 60% of the IVL and RA groups (p = 0.64) respectively. Final minimum stent area in distal LM (>8.2 mm2 ), ostial LAD (>6.3 mm2 ) and ostial LCX (>5.0 mm2 ) were achieved in 96%, 85% and 89% of cases treated with IVL respectively and 93%, 93% and 100% of cases treated with RA respectively (LM p = 1.00; LAD p = 0.62; LCX; p = 1.00 for difference between the two groups). Procedural success (technical success without in-hospital major adverse events) was achieved in 98% of the IVL group and 86% of the RA-only group (p = 0.04). There were eight procedural complications (flow-limiting dissection, perforation, or slow/no-reflow) in the RA group compared to four in the IVL group (NS), and one patient in the RA required salvaged mechanical support compared to none in the IVL group. CONCLUSION: Plaque modification with coronary IVL appears to be efficacious and safe for the treatment of severely calcified distal LM lesions compared to RA only. Larger randomized studies are needed to confirm these findings.

Impact of proximal cap ambiguity on the procedural techniques and outcomes of chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO Registry.

BACKGROUND: Proximal cap ambiguity is a key parameter in the global chronic total occlusion (CTO) percutaneous coronary intervention (PCI) crossing algorithm. METHODS: We examined the baseline characteristics and procedural outcomes of 9718 CTO PCIs performed in 9498 patients at 41 US and non-US centers between 2012 and 2022. RESULTS: Proximal cap ambiguity was present in 35% of CTO lesions. Patients whose lesions had proximal cap ambiguity were more likely to have had prior coronary artery bypass graft surgery (37% vs. 24%; p < 0.001). Lesions with proximal cap ambiguity were more complex with higher J-CTO score (3.1 ± 1.0 vs. 2.0 ± 1.2; p < 0.001) and lower technical (79% vs. 90%; p < 0.001) and procedural (77% vs. 89%; p < 0.001) success rates compared with nonambiguous CTO lesions. The incidence of major adverse cardiovascular events (MACE) was higher in cases with proximal cap ambiguity (2.5% vs. 1.7%; p < 0.001). The retrograde approach was more commonly used among cases with ambiguous proximal cap (50% vs. 21%; p < 0.001) and was more likely to be the final successful crossing strategy (29% vs. 13%; p < 0.001). The antegrade dissection and re-entry (ADR) "move-the-cap" techniques were also more common among cases with proximal cap ambiguity. CONCLUSIONS: Proximal cap ambiguity in CTO lesions is associated with higher utilization of the retrograde approach and ADR, lower technical and procedural success rates, and higher incidence of in-hospital MACE.

Impact of lesion length on the outcomes of chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: The impact of occlusion length on the procedural techniques and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We examined the clinical and angiographic characteristics and procedural outcomes of 10,335 CTO PCIs at 42 US and non-US centers between 2012 and 2022. The cohort was divided into two groups based on lesion length (≥20 mm vs. <20 mm). RESULTS: Long lesions were present in 7208 (70%) patients. Comorbidities were more common in patients with long CTOs. Compared with short lesions, long lesions had higher J-CTO score (2.8 ± 1.1 vs. 1.3 ± 1; p < 0.001) and retrograde wiring was more often the initial (15.5% vs. 4.0%; p < 0.001) and successful (22.8% vs. 8.2%; p < 0.001) crossing strategy. Long lesions were more likely to require longer procedure (123 vs. 91 min; p < 0.001) and fluoroscopy (47.1 vs. 32.2 min; p < 0.001) time, larger contrast volume (218 vs. 200 mL; p < 0.001) and higher air kerma radiation dose (2.4 vs. 1.7 Gy; p < 0.001). After adjusting for potential confounders, long lesions were associated with lower technical success (odds ratio [OR]: 0.91 per 10 mm increase; 95% confidence interval [CI]: 0.88, 0.94) and higher major adverse cardiovascular events (MACE) (OR: 1.08 per 10 mm increase; 95% CI: 1.02, 1.15). CONCLUSIONS: CTO PCI of long occlusions is independently associated with lower rates of technical success and higher rates of in-hospital MACE.

Aortocoronary dissection during percutaneous coronary interventions for chronic total occlusion: Insights from the PROGRESS-CTO registry.

BACKGROUND: Aortocoronary dissection is a potentially serious complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the incidence, mechanisms, treatment, and outcomes of aortocoronary dissection among 12,117 CTO PCIs performed between 2012 and 2022 in a large multicenter CTO PCI registry. RESULTS: The incidence of aortocoronary dissection was 0.2% (n = 27). Most aortocoronary dissections occurred in the right coronary artery (96.3%, n = 26). The baseline clinical characteristics of patients with and without aortocoronary dissection were similar, except for dyslipidemia, which was less common in patients with aortocoronary dissection (70.4% vs. 86.0%; p = 0.019). The retrograde approach was used more commonly among cases complicated by aortocoronary dissection (59.3% vs. 31.0%; p = 0.002). Technical (74.1% vs. 86.6%; p = 0.049) and procedural (70.4% vs. 85.2%; p = 0.031) success rates were lower among aortocoronary dissection cases, with a similar incidence of in-hospital major adverse cardiovascular events (3.7% vs. 2.0%; p = 0.541). Of the 27 patients with aortocoronary dissection, 19 (70.4%) were treated with ostial stenting and 8 (29.6%) were treated conservatively without subsequent adverse clinical outcomes. No patients required emergency surgery. Follow-up was available for 22 patients (81.5%): during a mean follow up of 767 (±562) days, the incidence of in-stent restenosis was 11.1% (n = 3). CONCLUSIONS: Aortocoronary dissection occurred in 0.2% of CTO PCIs performed by experienced operators, was associated with lower technical and procedural success, and was treated most commonly with ostial stenting. None of the patients required emergency cardiac surgery.

Same day discharge versus overnight observation following chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: Same day discharge (SDD) following chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We evaluated the clinical, angiographic, and procedural characteristics of patients discharged the same day versus those kept for overnight observation in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO, NCT02061436). RESULTS: Of the 7181 patients who underwent CTO PCI, 943 (13%) had SDD. The SDD rate increased from 3% in 2015 to 21% in 2022. Patients with SDD were less likely to have a history of heart failure (21% vs. 26%, p = 0.005), chronic lung disease (10% vs. 15%, p = 0.001), or anemia (12% vs. 19%, p < 0.001). Technical success (87% vs. 88%, p = 0.289) was similar, but in-hospital major adverse cardiovascular events (0.0% vs. 0.4%, p = 0.041) were lower in SDD. In multivariable logistic regression analysis, prior myocardial infarction odds ratio (OR): 0.71 (95% confidence interval [CI]: 0.59-0.87, p = 0.001), chronic lung disease OR: 0.64 (95% CI: 0.47-0.88, p = 0.006), and increasing procedure time OR: 0.93 (95% CI: 0.91-0.95, p < 0.001, per 10-min increase) were associated with overnight observation, while radial-only access OR: 2.45 (95% CI: 2.03-2.96, p < 0.001) had the strongest association with SDD. In the SDD, 2 (0.4%) of 514 patients were readmitted, due to retroperitoneal bleeding (n = 1) and ischemic stroke (n = 1). CONCLUSION: The overall frequency of SDD after CTO PCI was 13% and has been increasing over time. SDD is feasible in select patients following CTO PCI, and radial-only access had the strongest association with SDD.

Incidence, mechanisms, treatment, and outcomes of donor vessel injury during percutaneous coronary interventions for chronic total occlusion.

BACKGROUND: Donor vessel injury is a potentially life-threatening complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). AIMS: Our goal was to examine the incidence, mechanisms, treatment, and outcomes of patients with donor vessel injury in a large multicenter CTO PCI registry. METHODS: We analyzed the baseline clinical and angiographic characteristics, and procedural outcomes of 12,349 CTO PCIs performed between 2012 and 2022 at 44 centers. RESULTS: The incidence of donor vessel injury was 0.35% (n = 43). The baseline clinical characteristics of patients with and without donor vessel injury were similar. Cases complicated by donor vessel injury were more complex with higher Japanese CTO score (2.9 ± 1.1 vs. 2.4 ± 1.3; p = 0.004) and lower procedural success rate (69.8% vs. 85.2%; p = 0.004). The retrograde approach was used more commonly in donor vessel injury cases (68.9% vs. 30.9%; p < 0.001). Most (53.5%) donor vessel injuries were guide catheter-induced, whereas 20.9% were due to donor vessel thrombosis. Of the 43 patients with donor vessel injury, 36 (83.7%) were treated with stenting and seven (16.3%) received a left ventricular assist device. The incidence of major adverse cardiovascular events (MACEs) was significantly higher in cases with donor vessel injury (23.3% vs. 2.0%; p < 0.001). Of the 43 patients with donor vessel injury, five patients (11.6%) experienced acute myocardial infarction and four patients (9.3%) died. CONCLUSIONS: Donor vessel injury, occurred in 0.35% of CTO PCIs performed by experienced operators, was mainly due to guide catheter-induced dissection or thrombosis and was associated with lower procedural success and higher MACE.

Investigating the etiology of acute febrile illness: a prospective clinic-based study in Uganda.

BACKGROUND: Historically, malaria has been the predominant cause of acute febrile illness (AFI) in sub-Saharan Africa. However, during the last two decades, malaria incidence has declined due to concerted public health control efforts, including the widespread use of rapid diagnostic tests leading to increased recognition of non-malarial AFI etiologies. Our understanding of non-malarial AFI is limited due to lack of laboratory diagnostic capacity. We aimed to determine the etiology of AFI in three distinct regions of Uganda. METHODS: A prospective clinic-based study that enrolled participants from April 2011 to January 2013 using standard diagnostic tests. Participant recruitment was from St. Paul's Health Centre (HC) IV, Ndejje HC IV, and Adumi HC IV in the western, central and northern regions, which differ by climate, environment, and population density. A Pearson's chi-square test was used to evaluate categorical variables, while a two-sample t-test and Krukalis-Wallis test were used for continuous variables. RESULTS: Of the 1281 participants, 450 (35.1%), 382 (29.8%), and 449 (35.1%) were recruited from the western, central, and northern regions, respectively. The median age (range) was 18 (2-93) years; 717 (56%) of the participants were female. At least one AFI pathogen was identified in 1054 (82.3%) participants; one or more non-malarial AFI pathogens were identified in 894 (69.8%) participants. The non-malarial AFI pathogens identified were chikungunya virus, 716 (55.9%); Spotted Fever Group rickettsia (SFGR), 336 (26.2%) and Typhus Group rickettsia (TGR), 97 (7.6%); typhoid fever (TF), 74 (5.8%); West Nile virus, 7 (0.5%); dengue virus, 10 (0.8%) and leptospirosis, 2 (0.2%) cases. No cases of brucellosis were identified. Malaria was diagnosed either concurrently or alone in 404 (31.5%) and 160 (12.5%) participants, respectively. In 227 (17.7%) participants, no cause of infection was identified. There were statistically significant differences in the occurrence and distribution of TF, TGR and SFGR, with TF and TGR observed more frequently in the western region (p = 0.001; p < 0.001) while SFGR in the northern region (p < 0.001). CONCLUSION: Malaria, arboviral infections, and rickettsioses are major causes of AFI in Uganda. Development of a Multiplexed Point-of-Care test would help identify the etiology of non-malarial AFI in regions with high AFI rates.

Continuous flow mechanochemistry: reactive extrusion as an enabling technology in organic synthesis.

Rapid and wide-ranging developments have established mechanochemistry as a powerful avenue in sustainable organic synthesis. This is primarily due to unique opportunities which have been offered in solvent-free - or highly solvent-minimised - reaction systems. Nevertheless, despite elegant advances in ball-milling technology, limitations in scale-up still remain. This tutorial review covers the first reports into the translation from "batch-mode" ball-milling to "flow-mode" reactive extrusion, using twin-screw extrusion.

Definitions and Clinical Trial Design Principles for Coronary Artery Chronic Total Occlusion Therapies: CTO-ARC Consensus Recommendations.

Over the past 2 decades, chronic total occlusion (CTO) percutaneous coronary intervention has developed into its own subspecialty of interventional cardiology. Dedicated terminology, techniques, devices, courses, and training programs have enabled progressive advancements. However, only a few randomized trials have been performed to evaluate the safety and efficacy of CTO percutaneous coronary intervention. Moreover, several published observational studies have shown conflicting data. Part of the paucity of clinical data stems from the fact that prior studies have been suboptimally designed and performed. The absence of standardized end points and the discrepancy in definitions also prevent consistency and uniform interpretability of reported results in CTO intervention. To standardize the field, we therefore assembled a broad consortium comprising academicians, practicing physicians, researchers, medical society representatives, and regulators (US Food and Drug Administration) to develop methods, end points, biomarkers, parameters, data, materials, processes, procedures, evaluations, tools, and techniques for CTO interventions. This article summarizes the effort and is organized into 3 sections: key elements and procedural definitions, end point definitions, and clinical trial design principles. The Chronic Total Occlusion Academic Research Consortium is a first step toward improved comparability and interpretability of study results, supplying an increasingly growing body of CTO percutaneous coronary intervention evidence.

Development and validation of a prediction model for angiographic perforation during chronic total occlusion percutaneous coronary intervention: OPEN-CLEAN perforation score.

BACKGROUND: Perforation is the most frequent complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and is associated with adverse events including mortality. METHODS: Among 1,000 consecutive patients enrolled in 12 center prospective CTO PCI study (OPEN CTO), all perforations were reviewed by the angiographic core-lab. Eighty-nine patients (8.9%) with angiographic perforation were compared to 911 patients without perforation. We sought to describe the clinical and angiographic predictors of angiographic perforation during CTO PCI and develop a risk prediction model. RESULTS: Among eight clinically important candidate variables, independent risk factors for perforation included prior CABG (OR 2.0 [95% CI, 1.2-3.3], p < .01), occlusion length (OR 1.2 per 10 mm increase [95% CI, 1.1-1.3], p < .01), ejection fraction (OR 1.2 per 10% decrease [95% CI, 1.1-1.5], p < .01), age (OR 1.3 per 5 year increase [95%CI, 1.1-1.5], p < .01), and heavy calcification (OR 1.7 [95% CI, 1.0-2.7], p = .04). Three other potential candidate variables, glomerular filtration rate, proximal cap ambiguity, and target vessel, were not independently associated with perforation. The model was internally validated using bootstrapping methods. From the full model, a simplified perforation prediction score (OPEN-CLEAN score: CABG, Length [occlusion], EF < 50%, Age, CalcificatioN) was developed, which discriminated the risk of angiographic perforation well (c-statistics = 0.75) and demonstrated good calibration. CONCLUSION: This simple 5-variable prediction score may help CTO operators to risk-stratify patients for angiographic perforation using variables available prior to CTO PCI procedures.

Safety and efficacy of dedicated guidewire, microcatheter, and guide catheter extension technologies for chronic total coronary occlusion revascularization: Primary results of the Teleflex Chronic Total Occlusion Study.

BACKGROUND: Description of procedural outcomes using contemporary techniques that apply specialized coronary guidewires, microcatheters, and guide catheter extensions designed for chronic total occlusion (CTO) percutaneous revascularization is limited. METHODS: A prospective, multicenter, single-arm study was conducted to evaluate procedural and in-hospital outcomes among 150 patients undergoing attempted CTO revascularization utilizing specialized guidewires, microcatheters and guide extensions. The primary endpoint was defined as successful guidewire recanalization and absence of in-hospital cardiac death, myocardial infarction (MI), or repeat target lesion revascularization (major adverse cardiac events, MACE). RESULTS: The prevalence of diabetes was 32.7%; prior MI, 48.0%; and previous bypass surgery, 32.7%. Average (mean ± standard deviation) CTO length was 46.9 ± 20.5 mm, and mean J-CTO score was 1.9 ± 0.9. Combined radial and femoral arterial access was performed in 50.0% of cases. Device utilization included: support microcatheter, 100%; guide catheter extension, 64.0%; and mean number of study guidewires/procedure was 4.8 ± 2.6. Overall, procedural success was achieved in 75.3% of patients. The rate of successful guidewire recanalization was 94.7%, and in-hospital MACE was 19.3%. Achievement of TIMI grade 2 or 3 flow was observed in 93.3% of patients. Crossing strategies included antegrade (54.0%), retrograde (1.3%) and combined antegrade/retrograde techniques (44.7%). Clinically significant perforation resulting in hemodynamic instability and/or requiring intervention occurred in 16 (10.7%) patients. CONCLUSIONS: In a multicenter, prospective registration study, favorable procedural success was achieved despite high lesion complexity using antegrade and retrograde guidewire maneuvers and with acceptable safety, yet with comparably higher risk than conventional non-CTO PCI.

Radial access for chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

Use of radial access for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has been increasing. We examined the clinical characteristics and procedural outcomes of patients who underwent CTO PCI with radial versus femoral access in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO, NCT02061436). Of 10,954 patients who underwent CTO PCI at 55 centers in 7 countries between 2012 and 2022, 2578 (24%) had a radial only approach. Patients who underwent radial only access were younger (63 ± 10 vs. 65 ± 10, years, p &lt; 0.001), more likely to be men (84% vs. 81%, p = 0.001), and had significantly lower prevalence of comorbidities compared with the femoral access group including diabetes mellitus (39% vs. 45%, p &lt; 0.001) and coronary artery bypass graft surgery (57% vs. 64%, p &lt; 0.001). In addition, radial only cases had lower angiographic complexity with lower J-CTO and PROGRESS-CTO scores. After adjusting for potential confounders, radial only access was associated with lower risk of access site complications (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.22-0.91), similar technical success (OR: 0.87, 95% CI: 0.74-1.04) and major adverse cardiovascular events (MACE) (OR: 0.65, 95% CI: 0.40-1.07), compared with the femoral access group. Radial only access was used in 24% of CTO PCIs and was associated with lower access site complications, and similar technical success and MACE as compared with the femoral access group.

Antegrade dissection and re-entry versus parallel wiring in chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: The comparative efficacy and safety of parallel wiring versus antegrade dissection and re-entry (ADR) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is controversial. METHODS: We compared the clinical and angiographic characteristics and outcomes of parallel wiring versus ADR after failed antegrade wiring in a large, multicenter CTO PCI registry. RESULTS: A total of 1725 CTO PCI procedures with failed antegrade wiring with a single wire were approached with parallel wiring (692) or ADR (1033) at the discretion of the operator. ADR patients were older (65 ± 10 vs. 62 ± 10, years, p < 0.001) and had higher prevalence of comorbidities, such as diabetes mellitus (43% vs. 32%, p < 0.001), prior coronary artery bypass graft surgery (31% vs. 19%, p < 0.001), and lower left ventricular ejection fraction (50 ± 14 vs. 53 ± 11%, p < 0.001). The ADR group had higher J-CTO (2.8 ± 1.1 vs. 2.1 ± 1.3, p < 0.001) and PROGRESS-CTO (1.6 ± 1.1 vs. 1.2 ± 1.0, p < 0.001) scores. Equipment use including guidewires, balloons, and microcatheters was higher, and the procedures lasted longer in the ADR group. Technical success (78% vs. 75%, p = 0.046) and major adverse cardiovascular events (composite of all-cause mortality, stroke, acute myocardial infarction, emergency surgery or re-PCI, and pericardiocentesis) (3.7% vs. 1.9%, p = 0.029) were higher in the ADR group, with similar procedural success (75% vs. 73%, p = 0.166). CONCLUSION: In lesions that could not be crossed with antegrade wiring, ADR was associated with higher technical but not procedural success, and also higher MACE compared with parallel wiring.

Intravascular lithotripsy in chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: The use of intravascular lithotripsy (IVL) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We analyzed the baseline clinical and angiographic characteristics and procedural outcomes of 82 CTO PCIs that required IVL at 14 centers between 2020 and 2022. RESULTS: During the study period, IVL was used in 82 of 3301 (2.5%) CTO PCI procedures (0.4% in 2020 and 7% in 2022; p for trend < 0.001). Mean patient age was 69 ± 11 years and 79% were men. The prevalence of hypertension (95%), diabetes mellitus (62%), and prior PCI (61%) was high. The most common target vessel was the right coronary artery (54%), followed by the left circumflex (23%). The mean J-CTO and PROGRESS-CTO scores were 2.8 ± 1.1 and 1.3 ± 1.0, respectively. Antegrade wiring was the final successful crossing strategy in 65% and the retrograde approach was used in 22%. IVL was used in 10% of all heavily calcified lesions and 11% of all balloon undilatable lesions. The 3.5 mm lithotripsy balloon was the most commonly used balloon (28%). The mean number of pulses per lithotripsy run was 33 ± 32 and the median duration of lithotripsy was 80  (interquartile range: 40-103) seconds. Technical and procedural success was achieved in 77 (94%) and 74 (90%) cases, respectively. Two (2.4%) Ellis Class 2 perforations occurred after IVL use and were managed conservatively. CONCLUSION: IVL is increasingly being used in CTO PCI with encouraging outcomes.