Activated clotting time and outcomes of chronic total occlusion percutaneous coronary intervention: insights from the PROGRESS-CTO Registry.

BACKGROUND: The optimal range of activated clotting time (ACT) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We examined the association between ACT and in-hospital ischemic and bleeding outcomes in patients who underwent CTO PCI in the Prospective Global Registry for the Study of CTO Intervention. RESULTS: ACT values were available for 4377 patients who underwent CTO PCI between 2012 and 2023 at 29 centers. The mean ACT distribution was less than 250 seconds (19%), 250 to 349 seconds (50%), and greater than or equal to 350 seconds (31%). The incidence of ischemic events, bleeding events, and net adverse cardiovascular events (NACE) was 0.8%, 3.0%, and 3.8%, respectively. In multiple logistic regression analysis, increasing nadir ACT was associated with decreasing ischemic events (adjusted odds ratio [aOR] per 50-second increments: 0.69 [95% confidence interval (CI), 0.50-0.94; P=.017]; and increasing peak ACT was associated with increasing bleeding events (aOR per 50-second increments: 1.17 [95% CI ,1.01-1.36; P=.032]). A U-shaped association was seen between mean ACT and NACE, where restricted cubic spline analysis demonstrated that patients with a low ( less than 200 seconds) or high ( greater than 400 seconds) ACT had increasing NACE risk compared with an ACT of 200 to 400 seconds (aOR 2.06, 95% CI 1.18-3.62; P=.012). CONCLUSIONS: Among patients who underwent CTO PCI, mean ACT had a U-shaped relationship with NACE, where patients with a low ( less than 200 seconds) ACT (driven by ischemic events) or high ( greater than 400 seconds) ACT (driven by bleeding) had higher NACE compared with an ACT of 200 to 400 seconds.

Trends and Outcomes of Antegrade Dissection and Re-Entry in Chronic Total Occlusion Percutaneous Coronary Intervention.

BACKGROUND: The contemporary frequency and outcomes of antegrade dissection and re-entry (ADR) for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have received limited study. OBJECTIVES: The aim of this study was to determine the frequency and outcomes of ADR use in a large multicenter CTO PCI registry. METHODS: The characteristics and outcomes of ADR were examined among 12,568 patients who underwent 12,841 CTO PCIs at 46 U.S. and non-U.S. centers between 2012 and 2023. RESULTS: ADR was used in 2,385 of the procedures (18.6%). ADR use declined from 37.9% in 2012 to 14.5% in 2022 (P < 0.001). Patients in whom ADR was used had a high prevalence of comorbidities. Compared with cases that did not use ADR, ADR cases had more complex angiographic characteristics, higher mean J-CTO (Multicenter CTO Registry in Japan) score (2.94 ± 1.11 vs 2.23 ± 1.26; P < 0.001), lower technical success (77.0% vs 89.3%; P < 0.001), and higher in-hospital major adverse cardiac events (3.7% vs 1.6%; P < 0.001). The use of the CrossBoss declined from 71% in 2012 to 1.4% in 2022 and was associated with higher technical success (87%) compared with wire-based techniques (73%). The Stingray device displayed higher technical success (86%) compared with subintimal tracking and re-entry (STAR) (74%) and limited antegrade subintimal tracking (78%); however, its use has been decreasing, with STAR becoming the most used re-entry technique in 2022 (44% STAR vs 38% Stingray). CONCLUSIONS: The use of ADR has been decreasing. ADR was used in more complex lesions and was associated with lower technical success and higher major adverse cardiac events compared with non-ADR cases. There has been a decrease in Stingray use and an increase in the use of STAR for re-entry.

Impact of calcium on the procedural techniques and outcomes of chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Coronary calcification is common and increases the difficulty of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the impact of calcium on procedural outcomes of 13,079 CTO PCIs performed in 12,799 patients at 46 US and non-US centers between 2012 and 2023. RESULTS: Moderate or severe calcification was present in 46.6% of CTO lesions. Patients whose lesions were calcified were older and more likely to have had prior coronary artery bypass graft surgery. Calcified lesions were more complex with higher J-CTO score (3.0 ± 1.1 vs. 1.9 ± 1.2; p < 0.001) and lower technical (83.0% vs. 89.9%; p < 0.001) and procedural (81.0% vs. 89.1%; p < 0.001) success rates compared with mildly calcified or non-calcified CTO lesions. The retrograde approach was more commonly used among cases with moderate/severe calcification (40.3% vs. 23.5%; p < 0.001). Balloon angioplasty (76.6%) was the most common lesion preparation technique for calcified lesions, followed by rotational atherectomy (7.3%), laser atherectomy (3.4%) and, intravascular lithotripsy (3.4%). The incidence of major adverse cardiovascular events (MACE) was higher in cases with moderate or severe calcification (3.0% vs. 1.2%; p < 0.001), as was the incidence of perforation (6.5% vs. 3.4%; p < 0.001). On multivariable analysis, the presence of moderate/severe calcification was independently associated with lower technical success (odds ratio, OR = 0.73, 95% CI: 0.63-0.84) and higher MACE (OR = 2.33, 95% CI: 1.66-3.27). CONCLUSIONS: Moderate/severe calcification was present in nearly half of CTO lesions, and was associated with higher utilization of the retrograde approach, lower technical and procedural success rates, and higher incidence of in-hospital MACE.

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.

Development and validation of a scoring system for predicting clinical coronary artery perforation during percutaneous coronary intervention of chronic total occlusions: the PROGRESS-CTO perforation score.

BACKGROUND: Coronary artery perforation is a feared complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and often leads to serious adverse clinical events. AIMS: We sought to develop a risk score to predict clinical coronary artery perforation in patients undergoing CTO PCI. METHODS: We analysed clinical and angiographic parameters from 9,618 CTO PCIs in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO). Logistic regression prediction modelling was used to identify variables independently associated with clinical perforation, and the model was internally validated with bootstrapping. Clinical coronary artery perforation was defined as any perforation requiring treatment. RESULTS: The incidence of clinical coronary perforation was 3.8% (n=367). Five factors were independently associated with perforation and were included in the score: patient age ≥65 years +1 point (odds ratio [OR] 1.79, 95% confidence interval [CI]: 1.37-2.33), moderate/severe calcification +1 point (OR 1.85, 95% CI: 1.41-2.42), blunt/no stump +1 point (OR 1.45, 95% CI: 1.10-1.92), use of antegrade dissection and re-entry +1 point (OR 2.43, 95% CI: 1.61-3.69), and use of the retrograde approach +2 points (OR 4.02, 95% CI: 2.95-5.46). The resulting score showed acceptable performance on receiver operating characteristic (ROC) curve (area under the curve [AUC]: 0.741, 95% CI: 0.712-0.773). The Hosmer-Lemeshow test indicated a good fit (p=0.991), and internal validation with bootstrapping demonstrated good agreement with the model with observed AUC: 0.736 (95% bias-corrected CI: 0.706-0.767). CONCLUSIONS: The PROGRESS-CTO perforation score may be a useful tool for predicting clinical coronary perforation during CTO PCI.

Incidence, Mechanisms, Treatment, and Outcomes of Coronary Artery Perforation During Chronic Total Occlusion Percutaneous Coronary Intervention.

Coronary artery perforation is a feared complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Our objective was to describe the incidence, mechanisms, treatment, and outcomes of coronary artery perforation during CTO PCI. We analyzed the baseline clinical and angiographic characteristics and procedural outcomes of 10,454 CTO PCIs performed in 10,219 patients between 2012 and 2022. The incidence of coronary perforation was 4.9% (n = 503). Patients who experienced coronary perforation were older and were more likely to have had previous coronary artery bypass graft surgery. Procedures that resulted in perforation were more complex, with higher Japanese CTO and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) scores. Technical (66% vs 87%, p <0.001) and procedural (55% vs 87%, p <0.001) success rates were lower in perforation cases. The CTO target vessel was the most common perforation site (66%). The retrograde approach was responsible for the perforation in 47% of cases, and guidewire exit was the most common perforation mechanism. The proportion of Ellis class 1, 2, 3, and 3 -"cavity spilling" coronary perforations was 20%, 41%, 28%, and 11%, respectively. In 52% of perforations, 1 or more interventions were required: prolonged balloon inflation (23%), covered stent deployment (21%), coil embolization (6%), and/or autologous fat embolization (4%). Tamponade requiring pericardiocentesis occurred in 69 patients (14%). The incidence of major adverse cardiovascular events was higher in perforation cases (18% vs 1.3%, p <0.001). In conclusion, coronary artery perforation occurred in 4.9% of CTO PCIs performed by experienced operators and was associated with lower technical success and higher in-hospital major adverse cardiovascular events.

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.

Predictors of success in primary retrograde strategy in chronic total occlusion percutaneous coronary intervention: insights from the PROGRESS-chronic total occlusion registry.

BACKGROUND: An upfront (primary) retrograde strategy is often used in complex chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the clinical, angiographic characteristics, and procedural outcomes of CTO PCIs that were approached with a primary retrograde strategy in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO, NCT02061436). RESULTS: Of 10,286 CTO PCIs performed between 2012 and 2022, a primary retrograde strategy was used in 1329 (13%) with an initial technical success of 66%, and a final success of 83%. Patients who underwent successful versus unsuccessful primary retrograde cases had similar characteristics: age (65 ± 10 vs. 65 ± 9, years, p = 0.203), men (83% vs. 87%, p = 0.066), prior PCI (71% vs. 71%, p = 0.809), and prior coronary artery bypass graft surgery (52% vs. 53%, p = 0.682). The PROGRESS-CTO score (1.3 ± 0.9 vs. 1.6 ± 0.9, p < 0.001), air kerma radiation (3.9 ± 2.8 vs. 3.4 ± 2.6, gray, p = 0.013), and contrast use (294 ± 148 ml vs. 248 ± 128, ml, p < 0.001) were higher in the unsuccessful group, whereas the presence of interventional collaterals (95% vs. 72%, p < 0.001) and Werner collateral connection grade 2 (43% vs. 31%, p < 0.001) were higher in the successful group. On multivariable logistic regression analysis, the only variable associated with a successful primary retrograde strategy was the presence of interventional collaterals: odds ratio: 6.52 (95% confidence intervals; 3.5-12.1, p < 0.001). CONCLUSION: Presence of interventional collaterals is independently associated with higher success rates with a primary retrograde strategy in CTO PCI.

Venoarterial Extracorporeal Membrane Oxygenation in Cardiogenic Shock.

Venoarterial extracorporeal membrane oxygenation has emerged as a viable treatment for patients in cardiogenic shock with biventricular failure and pulmonary dysfunction. Advances in pump and oxygenator technology, cannulation strategies, patient selection and management, and durable mechanical circulatory support have contributed to expanded utilization of this technology. However, challenges remain that require investigation to improve outcomes.

Understanding the role of prostaglandin E2 in regulating human platelet activity in health and disease.

The platelet thrombus is the major pathologic entity in acute coronary syndromes, and antiplatelet agents are a mainstay of therapy. However, individual patient responsiveness to current antiplatelet drugs is variable, and all drugs carry a risk of bleeding. An understanding of the complex role of Prostaglandin E2 (PGE2) in regulating thrombosis offers opportunities for the development of novel individualized antiplatelet treatment. However, deciphering the platelet regulatory function of PGE2 has long been confounded by non-standardized experimental conditions, extrapolation of murine data to humans, and phenotypic differences in PGE2 response. This review synthesizes past and current knowledge about PGE2 effects on platelet biology, presents a rationale for standardization of experimental protocols, and provides insight into a molecular mechanism by which PGE2-activated pathways could be targeted for new personalized antiplatelet therapy to inhibit pathologic thrombosis without affecting hemostasis.

Suboptimal inhibition of platelet cyclooxygenase-1 by aspirin in metabolic syndrome.

Interindividual variation in the ability of aspirin to inhibit platelet cyclooxygenase-1 (COX-1) could account for some on-treatment cardiovascular events. Here, we sought to determine whether there are clinical phenotypes that are associated with a suboptimal pharmacological effect of aspirin. In a prospective, 2-week study, we evaluated the effect of aspirin (81 mg) on platelet COX-1 in 135 patients with stable coronary artery disease by measuring serum thromboxane B(2) (sTxB(2)) as an indicator of inhibition of platelet COX-1. A nested randomized study compared enteric-coated with immediate-release formulations of aspirin. We found that sTxB(2) was systematically higher among the 83 patients with metabolic syndrome than among the 52 patients without (median: 4.0 versus 3.02 ng/mL; P=0.013). Twelve patients (14%) with metabolic syndrome, but none without metabolic syndrome, had sTxB(2) levels consistent with inadequate inhibition of COX (sTxB(2) ≥13 ng/mL). In linear regression models, metabolic syndrome (but none of its individual components) significantly associated with higher levels of log-transformed sTxB(2) (P=0.006). Higher levels of sTxB(2) associated with greater residual platelet function measured by aggregometry-based methods. Among the randomized subset, sTxB(2) levels were systematically higher among patients receiving enteric-coated aspirin. Last, urinary 11-dehydro thromboxane B(2) did not correlate with sTxB(2), suggesting that the former should not be used to quantitate aspirin's pharmacological effect on platelets. In conclusion, metabolic syndrome, which places patients at high risk for thrombotic cardiovascular events, strongly and uniquely associates with less effective inhibition of platelet COX-1 by aspirin.

PGE2 decreases reactivity of human platelets by activating EP2 and EP4.

INTRODUCTION: Platelet hyperreactivity associates with cardiovascular events in humans. Studies in mice and humans suggest that prostaglandin E2 (PGE2) regulates platelet activation. In mice, activation of the PGE2 receptor subtype 3 (EP3) promotes thrombosis, but the significance of EP3 in humans is less well understood. OBJECTIVES: To characterize the regulation of thromboxane-dependent human platelet activation by PGE2. PATIENTS/METHODS: Platelets collected from nineteen healthy adults were studied using an agonist of the thromboxane receptor (U46,619), PGE2, and selective agonists and/or antagonists of the EP receptor subtypes. Platelet activation was assayed by (1) optical aggregometry, (2) measurement of dense granule release, and (3) single-platelet counting. RESULTS: Healthy volunteers demonstrated significant interindividual variation in platelet response to PGE2. PGE2 completely inhibited U46,619-induced platelet aggregation and ATP release in 26% of subjects; the remaining 74% had partial or no response to PGE2. Antagonism of EP4 abolished the inhibitory effect of PGE2. In all volunteers, a selective EP2 agonist inhibited U46,619-induced aggregation. Furthermore, the selective EP3 antagonist DG-041 converted all PGE2 nonresponders to full responders. CONCLUSIONS: There is significant interindividual variation of platelet response to PGE2 in humans. The balance between EP2, EP3, and EP4 activation determines its net effect. PGE2 can prevent thromboxane-induced platelet aggregation in an EP4-dependent manner. EP3 antagonism converts platelets of nonresponders to a PGE2-responsive phenotype. These data suggest that therapeutic targeting of EP pathways may have cardiovascular benefit by decreasing platelet reactivity.

Recovery following propofol-associated brugada electrocardiogram.

Brugada syndrome is a genetic disorder associated with an increased risk of sudden cardiac death that has typical electrocardiographic (ECG) patterns. Recently, there have been reports of Brugada ECG patterns seen in critically ill patients who received propofol,(1) and this pattern was associated with a very high imminent mortality. We report a case in which a critically ill patient developed a Brugada ECG pattern following high-dose propofol infusion. Once the ECG pattern was recognized, the propofol was discontinued and the ECG pattern resolved, and the patient was discharged home with no arrhythmic sequelae.