Ranolazine in chronic total occlusion percutaneous coronary intervention.

Ranolazine is an anti-anginal medication given to patients with chronic angina and persistent symptoms despite medical therapy. We examined 11 491 chronic total occlusion (CTO) percutaneous coronary interventions (PCI) that were performed at 41 US and non-US centers between 2012 and 2023 in the PROGRESS-CTO Registry. Patients on ranolazine at baseline had more comorbidities, more complex lesions, lower procedural and technical success (based on univariable but not multivariable analysis), and higher incidence of major adverse cardiac events (MACE) (on both univariable and multivariable analysis).

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.

Implementation of a Comprehensive ST-Elevation Myocardial Infarction Protocol Improves Mortality Among Patients With ST-Elevation Myocardial Infarction and Cardiogenic Shock.

Mortality in patients with STEMI-associated cardiogenic shock (CS) is increasing. Whether a comprehensive ST-elevation myocardial infarction (STEMI) protocol (CSP) can improve their care delivery and mortality is unknown. We evaluated the impact of a CSP on incidence and outcomes in patients with STEMI-associated CS. We implemented a 4-step CSP including: (1) Emergency Department catheterization lab activation; (2) STEMI Safe Handoff Checklist; (3) immediate catheterization lab transfer; (4) and radial-first percutaneous coronary intervention (PCI). We studied 1,272 consecutive STEMI patients who underwent PCI and assessed for CS incidence per National Cardiovascular Data Registry definitions within 24-hours of PCI, care delivery, and mortality before (January 1, 2011, to July 14, 2014; n = 723) and after (July 15, 2014, to December 31, 2016; n = 549) CSP implementation. Following CSP implementation, CS incidence was reduced (13.0% vs 7.8%, p = 0.003). Of 137 CS patients, 43 (31.4%) were in the CSP group. CSP patients had greater IABP-Shock II risk scores (1.9 ± 1.8 vs 2.8 ± 2.2, p = 0.014) with otherwise similar hemodynamic and baseline characteristics, cardiac arrest incidence, and mechanical circulatory support use. Administration of guideline-directed medical therapy was similar (89.4% vs 97.7%, p = 0.172) with significant improvements in trans-radial PCI (9.6% vs 44.2%, p < 0.001) and door-to-balloon time (129.0 [89:160] vs 95.0 [81:116] minutes, p = 0.001) in the CSP group, translating to improvements in infarct size (CK-MB 220.9 ± 156.0 vs 151.5 ± 98.5 ng/ml, p = 0.005), ejection fraction (40.8 ± 14.5% vs 46.7 ± 14.6%, p = 0.037), and in-hospital mortality (30.9% vs 14.0%, p = 0.037). In conclusion, CSP implementation was associated with improvements in CS incidence, infarct size, ejection fraction, and in-hospital mortality in patients with STEMI-associated CS. This strategy offers a potential solution to bridging the historically elusive gap in their care.

A complex regulatory network coordinating cell cycles during C. elegans development is revealed by a genome-wide RNAi screen.

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development.