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Background: Tricuspid regurgitation (TR) and mitral regurgitation (MR) are common valvular conditions encountered in patients undergoing transcatheter aortic valve replacement (TAVR). This retrospective study investigates the impact of moderate or severe TR and MR on all-cause mortality in one-year post-TAVR patients., Methods: Consecutive patients who underwent TAVR at the 3 academic tertiary care centers in our health system between 2012 and 2018 were identified. Patients were stratified into 2 groups based on valvular regurgitation severity: moderate/severe MR vs. no/mild MR, and moderate/severe TR vs. no/mild TR. Primary outcome was all-cause mortality at 1-year and 5-year follow up, and secondary outcome was in-hospital death. Logistic regression analysis was conducted to assess the relationship between moderate/severe MR or TR and all-cause mortality at 1-year and 5-year follow-up., Results: We included a total of 1,071 patients who underwent TAVR with mean age 80.9 ± 8.6 years, 97% white, and 58.3% males. Moderate or severe MR group included 52 (4.88%) patients while mild or no MR group included 1,015 (95.12%) patients. There was no significant difference between both groups in TAVR procedure success rate (100% vs. 97.83%, p=0.283), in-hospital mortality (0 vs. 1.08%, p=0.450), or mortality at 1-year follow up (15.38% vs. 14.09%, p=0.794). At 5-year follow up, moderate/severe MR group had higher mortality (61.4% vs. 49.5%, p=0.046). In multivariable logistic regression analysis, moderate or severe MR did not show significant correlation with all-cause mortality at 1-year and 5-year follow up. Moderate or severe TR group included 86 (8.03%) patients while mild or no TR group included 985 (91.97%) patients. There was no difference between both groups in TAVR procedure success (98.8% vs. 97.9%, p=0.54) or in-hospital mortality (0% vs. 1.1%, p=0.33). At 1-year follow up, patients with moderate or severe TR had higher mortality (26.7% vs. 13.2%, p=0.001) compared to patients with mild or no TR. Same finding was noted with extended follow up at 5-years (68.3% vs. 48.7%, p<0.001). In multivariable cox regression analysis, moderate/severe TR was associated with higher all-cause mortality at 1-year (OR 1.94, 95% CI [01.09, 3.44], p=0.0.023) and at 5-year (OR 1.46, 95% CI [1.092, 1.952], p=0.0.011) follow up. Patients with combined moderate/severe MR and TR have even higher mortality compared to either moderate/severe valve regurgitation alone or mild/no valve regurgitation at 5-year follow up., Conclusion: At long term follow up, moderate/severe TR, but not MR, is associated with higher mortality in patients underwent TAVR. Combined moderate/severe TR and MR had even worse mortality. Careful assessment of multi-valvular heart disease prior to the procedure is warranted., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To examine the characteristics and outcomes of myocardial infarction (MI) among burn patients., Materials and Methods: The Nationwide Readmissions Database was utilized to identify hospitalizations of patients with burns from 2016 to 2020. The main outcome was the difference in all-cause in-hospital mortality between burn patients with and without MI., Results: Of 200,130 hospitalizations with burns, 1997 (1 %) developed acute MI. Burn patients with MI were older, more likely to be men, and had a higher prevalence of cardiovascular risk factors. Only burns affecting the trunk and respiratory tract, and those affecting > 20 % of body surface area (BSA), were associated with an increased risk of MI. All-cause in-hospital mortality was higher among patients with MI (18.7 % vs. 3 %, adjusted odds ratio (aOR) 4.59, 95 % confidence interval (CI) 3.66, 5.76). Cardiogenic shock, ventricular tachycardia, and stroke rates were higher among patients with MI. Revascularization was associated with lower in-hospital mortality (aOR 0.33, 95 % CI 0.17, 0.64) CONCLUSIONS: The incidence of MI in burn patients is low but is associated with high mortality and morbidity. Burns involving the trunk and respiratory tract, and those affecting > 20 % BSA, were associated with an increased risk of MI. Revascularization was associated with lower in-hospital mortality., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients experiencing loss of pulse pressure (LOPP) during high-risk percutaneous coronary intervention (HR-PCI) are transiently dependent on mechanical circulatory support devices. We sought to define the frequency and clinic outcomes of patients who experience LOPP during HR-PCI., Methods and Results: Patients enrolled in the PROTECT III study and had automated Impella controller logs capturing real-time hemodynamics were included in this analysis. A LOPP event was defined as a mean pulse pressure on Impella of <20 mm Hg for ≥5 seconds during PCI. Clinical characteristics and outcomes were then compared between those with and without LOPP. Logistic regression identified clinical and hemodynamic predictors of LOPP. We included 302 patients, of whom 148 patients (49%) experienced LOPP. Age, sex, and comorbidities were similar in patients with and without LOPP. Mean baseline systolic blood pressure (118.6 mm Hg vs 129.8 mm Hg; P < .001) and mean arterial pressure (86.9 mm Hg vs 91.6 mm Hg; P = .011) were lower in patients with LOPP, whereas heart rate (78 bpm vs 73 bpm; P = .012) was higher. Anatomical complexity was similar between groups. Patients with LOPP were more likely to experience major adverse cardiac and cerebrovascular events (23.5% vs 8.8%; P = .002), acute kidney injury (10.1% vs 2.6%; P = .030), and death (20.2% vs 7.9%; P = .008) within 90 days. A low baseline systolic blood pressure and cardiomyopathy were the strongest predictors of LOPP (P = .003 and P = .001, respectively)., Conclusions: LOPP on Impella during HR-PCI was common and occurred more frequently in patients with cardiomyopathy and a low systolic blood pressure. LOPP was strongly associated with higher 90-day major adverse cardiac and cerebrovascular events, acute kidney injury, and mortality. Condensed Abstract We sought to define the frequency and clinic outcomes of patients who experience LOPP during high-risk percutaneous coronary intervention (HR-PCI). We included 302 patients, of whom 148 (49%) experienced LOPP. Patients with LOPP were more likely to experience major adverse cardiac and cerebrovascular events (23.5% vs 8.8%; P = .002), acute kidney injury (10.1% vs 2.6%; P = .030), and death (20.2% vs 7.9%; P = .008) within 90 days. A low baseline systolic blood pressure and cardiomyopathy were the strongest predictors of LOPP (P = .003 and P = .001, respectively)., Competing Interests: Disclosures Mir B. Basir is a consultant for Abiomed, Boston Scientific, Chiesi, Saranas and Zoll. Dana Bentley is an employee of Abiomed. Alexander G. Truesdell is a consultant/speaker for Abiomed and a speaker for Shockwave. Katherine Kunkel is a consultant and speaker for Abiomed and Shockwave Medical, speaker for Cardiovascular Systems Incorporated, and consultant for Medtronic and Bristol Myers Squibb/Janssen. Alejandro Lemor discloses a speaker honorarium from Abiomed. Michael Megaly has no disclosures. Mohammad Alqarqaz discloses an institutional research grant from Abiomed. Khaldoon Alaswad is a consultant and speaker for BSC, Teleflex, and CSI. Akshay Khandewal has no disclosures. Elise Jortberg is an employee of Abiomed. Sanjog Kalra is a consultant for Abiomed, Boston Scientific, Philips Healthcare, Cardiovascular Systems, and Translumina Therapeutics; on the advisory board for Abiomed, Boston Scientific, Philips Healthcare, Medtronic, and Avinger; on the speaker's bureau for Abiomed, Boston Scientific, Philips Healthcare, Cardiovascular Systems, Translumina Therapeutics, and Medtronic; a sponsored research participant for Abiomed, Boston Scientific, and Philips Healthcare; and a proctor for Boston Scientific, Philips Healthcare, and Translumina Therapeutics. Amir Kaki is a speaker/proctor for Abiomed, Abbott, Boston Scientific, CSI, Medtronic, and Terumo. Daniel Burkhoff is on the Steering Committee for RECOVER IV sponsored by Abiomed (institutional compensation). Jeffrey W. Moses received honoraria or consulting fees from Abiomed, Philips, and Boston Scientific. Duane S. Pinto received honoraria or consulting fees from Abiomed, Abbott Vascular, Haemonetics, CSL Behring, Biotronik, Shockwave, Terumo, and Medtronic. Gregg W. Stone discloses that he has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; has served as a consultant to Abbott, Daiichi Sankyo, Ablative Solutions, CorFlow, Apollo Therapeutics, Cardiomech, Gore, Robocath, Miracor, Vectorious, Abiomed, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, Cardiac Success, HighLife; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr. Stone's employer, Mount Sinai Hospital, receives research grants from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Family disclosure: Dr. Stone's daughter is an employee at IQVIA. William W. O'Neill is a consultant to Abiomed, Zoll, and Edwards Lifesciences., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Despite optimal medical therapy and cardiac resynchronization therapy (CRT), significant functional mitral regurgitation (MR) persisted in 30% of the patients and labeled as CRT nonresponders., Aims: We sought to study the impact of transcatheter edge-to-edge repair (TEER) in patients with symptomatic grade III and IV functional MR despite CRT., Methods: A retrospective analysis was conducted of all patients who had prior CRT for at least 6 months and underwent TEER for significant residual functional MR (grade ≥3) and symptomatic heart failure (HF) at our institution. The primary outcomes were the change in New York Heart Association classification (NYHA), MR grade, echo parameters, and NT-ProBNP from baseline to 1-year post-procedure., Results: A total of 28 patients were identified, mean age of 73 ± 6.7 years and 89% males. Procedure success was achieved in all patients. At 1-year follow-up, patients had lower MR grade (median 2, IQR 1 [1,2] vs. 4, IQR 1 [3,4]; p < 0.001), NYHA class (median 2, IQR 1 [2,3] vs. 3, IQR 1 [3,4]; p < 0.001), and NT-ProBNP (7658 ± 11322 vs. 3760 ± 4431; p = 0.035) compared to before the TEER procedure. The left ventricular end-diastolic volume (255 ± 59 vs. 244 ± 66 mm; p = 0.016) and the right ventricular systolic pressure (52 ± 14 mmHg vs. 37 ± 13 mmHg, <0.001) decreased., Conclusion: Patients who remain symptomatic after CRT with severe functional MR had improved functional status and MR grade at 1-year following TEER. There was a signal toward reverse remodeling., (© 2024 Wiley Periodicals LLC.)

Objective: To examine the characteristics and outcomes of acute myocardial infarction (AMI) in patients with bleeding and/or hypercoagulable disorders., Background: Studies examining the outcomes of AMI in bleeding/hypercoagulable disorders are scarce., Methods: The Nationwide Readmissions Database was utilized to identify hospitalizations with AMI from 2016 to 2020. The study cohort was divided into 4 groups: (1) MI without bleeding or hypercoagulable disorders, (2) MI with bleeding disorders, (3) MI with hypercoagulable disorders and (4) MI with mixed disorders. The main outcome was all-cause in-hospital mortality., Results: A total of 4,206,005 weighted hospitalizations with AMI were identified during the study period, of which 382,118 (9.1 %) had underlying bleeding or hypercoagulable disorders. The utilization of invasive strategies for the management of MI was highest in patients without bleeding or hypercoagulable disorders (62.6 %) and lowest in patients with mixed disorders (39.3 %). In-hospital mortality was higher among patients with bleeding (adjusted odds ratio [OR] 1.22; 95 % confidence interval [CI] 1.21, 1.24) and mixed disorders (aOR 3.38; 95 % CI 3.27, 3.49) compared with patients without bleeding or hypercoagulable disorders. Among patients with any bleeding or hypercoagulable disorder, those who underwent invasive strategy had lower adjusted odds of in-hospital mortality (aOR 0.28; 95 % CI 0.27, 0.30), ischemic stroke (aOR 0.60; 95 % CI 0.56, 0.64), bleeding (aOR 0.63; 95 % CI 0.61, 0.65), blood transfusion (aOR 0.95; 95 % CI 0.91, 0.99) and 30-day urgent readmissions (aOR 0.70; 95 % CI 0.68, 0.72)., Conclusions: The inpatient management and outcomes of AMI in patients with bleeding/hypercoagulable disorders differ from patients without those disorders. Revascularization in the setting of AMI was associated with lower in-hospital mortality, which suggests that patients with bleeding/hypercoagulable disorders can be evaluated for standard approaches to managing AMI; however, confounding by indication may be a concern., Competing Interests: Declaration of competing interest All other authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Notch receptor is a pleiotropic signaling protein that translates intercellular ligand interactions into changes in gene expression via the nuclear localization of the Notch intracellular Domain (NICD). Using a combination of immunohistochemistry, RNA in situ, Optogenetics and super-resolution live imaging of transcription in human cells, we show that the N1ICD can form condensates that positively facilitate Notch target gene expression. We determined that N1ICD undergoes Phase Separation Coupled Percolation (PSCP) into transcriptional condensates, which recruit, enrich, and encapsulate a broad set of core transcriptional proteins. We show that the capacity for condensation is due to the intrinsically disordered transcriptional activation domain of the N1ICD. In addition, the formation of such transcriptional condensates acts to promote Notch-mediated super enhancer-looping and concomitant activation of the MYC protooncogene expression. Overall, we introduce a novel mechanism of Notch1 activity in which discrete changes in nuclear N1ICD abundance are translated into the assembly of transcriptional condensates that facilitate gene expression by enriching essential transcriptional machineries at target genomic loci., (© 2024. Crown.)

Background: Higher rates of CIED implantations have been associated with an increased rate of lead failures and complications resulting in higher rates of transvenous lead extractions (TLE)., Objective: To assess the trends TLE admissions and evaluate the patient related predictors of safety outcomes., Methods: National Readmission Database was queried to identify patients who underwent TLE from January 2016 to December 2019. We conducted a multivariate regression analysis to identify variables associated with in-hospital mortality in patients undergoing TLE. Additionally, we compared trends and outcomes of TLE among patients with prior sternotomy versus those without prior sternotomy and analyzed sex-based differences among patients undergoing TLE., Results: We identified 30,128 hospitalizations for TLE. The index admission in-hospital mortality rate was 3.21% with cardiac tamponade happening in 1.46% of the admissions. Age, infective endocarditis, CKD, congestive heart failure and anemia were associated with higher in-hospital mortality rates. There was a lower rate of in-hospital mortality in patients with history of prior sternotomy versus patients without (OR 0.72, CI: 0.59-0.87, p-value < 0.001). There was no difference in in-hospital mortality rate between males and females. Females had a shorter length and a higher cost of stay when compared to male gender., Conclusion: TLE admissions continue to increase. Overall rates of mortality and complications are relatively low. Patients with prior sternotomy had better outcomes and less complications when compared to those without prior sternotomy. Female gender is associated with higher rates of cardiac tamponade, yet shorter length of stay with lower cost., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Drosophila melanogaster has been used as a model system to identify and characterize genetic contributions to development, homeostasis, and to investigate the molecular determinants of numerous human diseases. While there exist many differences at the genetic, structural, and molecular level, many signalling components and cellular machineries are conserved between Drosophila and humans. For this reason, Drosophila can and has been used extensively to model, and study human pathologies. The extensive genetic resources available make this model system a powerful one. Over the years, the sophisticated and rapidly expanding Drosophila genetic toolkit has provided valuable novel insights into the contribution of genetic components to human diseases. The activity of Notch signalling is crucial during development and conserved across the Metazoa and has been associated with many human diseases. Here we highlight examples of mechanisms involving Notch signalling that have been elucidated from modelling human diseases in Drosophila melanogaster that include neurodegenerative diseases, congenital diseases, several cancers, and cardiac disorders., Competing Interests: The authors declare there are no conflicts of interest., (© 2024 The Author(s). Published by IMR Press.)

Coronary chronic total occlusions (CTO) are present in up to one-third of patients with coronary artery disease (CAD). It is thus essential for all clinical cardiologists to possess a basic awareness and understanding of CTOs, including optimal evaluation and management. While percutaneous coronary intervention (PCI) for CTO lesions has many similarities to non-CTO PCI, there are important considerations pertaining to pre-procedural evaluation, interventional techniques, procedural complications, and post-procedure management and follow-up unique to patients undergoing this highly specialized intervention. Distinct from other existing topical reviews, the current manuscript focuses on key knowledge relevant to non-interventional cardiologists., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Cilia, Megaly, Davies, Tehrani, Batchelor and Truesdell.)

Objective: To examine the characteristics and outcomes among patients with high-risk pulmonary embolism (PE) and malignancy., Patients and Methods: The Nationwide Readmissions Database was used to identify hospitalizations with high-risk PE from January 1, 2016, to December 31, 2019. The main outcome was the difference in all-cause in-hospital mortality., Results: Among 28,547 weighted hospitalizations with high-risk PE, 4,825 (16.9%) had malignancy. Admissions with malignancy had a lower prevalence of other comorbid conditions except for anemia and coagulopathy. The use of systemic thrombolysis, catheter-directed interventions, and surgical embolectomy was less common among admissions with malignancy, whereas the use of inferior vena cava filter was more common among those with malignancy. All-cause in-hospital mortality was higher among admissions with malignancy even after adjustment (adjusted odds ratio, 1.91; 95% CI, 1.72 to 2.11; P<.001). Metastatic genitourinary, gastrointestinal (other than colorectal), and lung malignancies were associated with the highest incidence of in-hospital mortality. The incidence of intracranial hemorrhage (3.9% vs 3.1%; P=.056) and the composite of non-intracranial hemorrhage bleeding (21.9% vs 20.6%; P=.185) was not different between admissions with and without malignancy. However, admissions with malignancy had higher incidence of gastrointestinal bleeding., Conclusion: In this nationwide analysis of patients admitted with high-risk PE, malignancy was independently associated with an increased risk of in-hospital mortality. The risk was highest among patients with metastatic genitourinary, gastrointestinal, and lung malignancies. Advanced therapies were less frequently used among patients with malignancy., (Published by Elsevier Inc.)

Objective: To determine the value of ordering a routine chest CT (CCT) in patients with blunt trauma presenting to the emergency department with a high GCS and low ISS, we retrospectively collected patient data including CT scan results, when physical examination and initial chest X-ray were normal in the trauma bay area., Methods: A retrospective data collection of 901 consecutive blunt trauma patients seen in the ED between 2017 and 2019 was analyzed. Data included physical examination, age, gender, current use of anticoagulation therapy, comorbid conditions, as well as the result of radiologic images, hospital length of stay, surgical intervention, and mortality. The patients were divided into two groups: group one (patients with negative physical examination; chest x-ray and CT) and group 2 (negative physical examination, positive or negative chest x-ray, and positive CT). Statistical analysis was performed using student's t-test and chi-square test., Results: Of the 901 patients there were 489 (54%) males and 412 (46%) females with a mean age of 56 years. There were 461 patients who had a physical examination, chest x-ray, abdominal and CCT done. Group one included 442 (96%) patients, with negative physical examination, negative chest X-ray and CT scan. In group 2, 19 (4%) patients who had positive CT and or chest x-ray. Both groups were similar in GCS and ISS. Of the 19 patients, sixteen patients had a positive CCT, and thirteen of those had a positive chest x-ray. In the three patients who had negative physical examination and chest x-ray, the CT findings included one with a nondisplaced 10th rib fracture and two patients with osteoporotic compression fractures of dorsal vertebrae. The rate of both chest x-ray and CCT being positive among a group of screened patients was 16% (3/19) and the rate of a negative chest x-ray but positive CT was 16% (3/19). The odds ratio between the two outcomes was one., Conclusion: In blunt trauma patients presenting to the ED with a high GCS and low ISS score, when initial physical examination and chest x-ray are negative, routine CCT is of little value., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A 72-year-old woman presented with progressive angina and anterior ischemia on a nuclear stress test.

Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare.

The outcomes of chronic total occlusion (CTO) percutaneous coronary interventions (PCIs) in patients with previous coronary artery bypass graft (CABG) surgery have received limited study. We examined the baseline characteristics and outcomes of CTO PCIs performed at 47 United States and non-United States centers between 2012 and 2023. Of the 12,164 patients who underwent CTO PCI during the study period, 3,475 (29%) had previous CABG. Previous CABG patients were older, more likely to be men, and had more comorbidities and lower left ventricular ejection fraction and estimated glomerular filtration rate. Their CTOs were more likely to have moderate/severe calcification and proximal tortuosity, proximal cap ambiguity, longer lesion length, and higher Japanese CTO scores. The first and final successful crossing strategy was more likely to be retrograde. Previous CABG patients had lower technical (82.1% vs 88.2%, p <0.001) and procedural (80.8% vs 86.8%, p <0.001) success, higher in-hospital mortality (0.8% vs 0.3%, p <0.001), acute myocardial infarction (0.9% vs 0.5%, p = 0.007) and perforation (7.0% vs 4.2%, p <0.001) but lower incidence of pericardial tamponade and pericardiocentesis (0.1% vs 1.3%, p <0.001). At 2-year follow-up, the incidence of major adverse cardiac events, repeat PCI and acute coronary syndrome was significantly higher in previous CABG patients, whereas all-cause mortality was similar. In conclusion, patients with previous CABG who underwent CTO PCI had more complex clinical and angiographic characteristics and lower success rate, higher perioperative mortality, and myocardial infarction but lower tamponade, and higher incidence of major adverse cardiac events with similar all-cause mortality during follow-up., Competing Interests: Declaration of Competing Interest Dr. Choi reports as Medtronic advisory board. Dr. Poommipanit reports as consultant for Asahi Intecc, and Abbott Vascular. Dr. Alaswad reports as consultant and speaker for Boston Scientific, Abbott Cardiovascular, Teleflex, and Cardiovascular Systems Inc. Dr. Rinfret reports as consultant for Boston Scientific, Teleflex, Medtronic, Abbott, and Abiomed. Dr. Basir reports as consultant for Abbott Vascular, Abiomed, Cardiovascular Systems, Inc, Chiesi, and Zoll. Dr. Khatri has received personal honoraria for proctoring and speaking fees from Abbott Vascular, Medtronic, Terumo, Shockwave, and Boston Scientific. Dr. Karmpaliotis has received honoraria from Boston Scientific and Abbott Vascular and has equity in Saranas, SoundBite Medical, and Traverse Vascular. Dr. Nicholson has been a proctor for and on the speaker's bureau and advisory boards for Abbott Vascular, Boston Scientific, and Asahi Intecc; and he reports intellectual property with Vascular Solutions. Dr. Davies reports as speaking honoraria from Abiomed, Asahi Intec, Boston Scientific, Medtronic, Teleflex, and Shockwave Medical. She also serves on advisory boards for Abiomed, Avinger, Boston Scientific, Medtronic, and Rampart. Dr. Jaffer has done sponsored research for Canon, Siemens, Shockwave, Teleflex, Mercator, and Boston Scientific; and has been a consultant for Boston Scientific, Siemens, Magenta Medical, IMDS, Asahi Intecc, Biotronik, Philips, and Intravascular Imaging Inc. He has equity interest in Intravascular Imaging Inc, DurVena; and the right to receive royalties through Massachusetts General Hospital licensing arrangements with Terumo, Canon, and Spectrawave. Dr. Azzalini received consulting fees from Teleflex, Abiomed, GE Healthcare (Little Chalfont, United Kingdom), Asahi Intecc, Philips, Abbott Vascular, Reflow Medical, and Cardiovascular Systems, Inc. Dr. ElGuindy reports as consulting honoraria: Medtronic, Boston Scientific, Asahi Intecc, Terumo; Proctorship fees: Medtronic, Boston Scientific, Asahi Intecc, Terumo. Dr. Abi‐Rafeh: Proctor and speaker honoraria from Boston Scientific and Shockwave Medical. Dr. Allana: consulting for Boston Scientific Corporation and Abiomed. Dr. Sandoval: previously served on the Advisory Boards for Roche Diagnostics and Abbott Diagnostics without personal compensation; and has also been a speaker without personal financial compensation for Abbott Diagnostics. Dr. Burke: consulting and speaker honoraria from Abbott Vascular and Boston Scientific. Dr. Brilakis: consulting/speaker honoraria from Abbott Vascular, American Heart Association (associate editor Circulation), Amgen, Asahi Intecc, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), CSI, Elsevier, GE Healthcare, IMDS, Medicure, Medtronic, Siemens, Teleflex, and Terumo; research support: Boston Scientific, GE Healthcare; owner, Hippocrates LLC; shareholder: MHI Ventures, Cleerly Health, Stallion Medical. Dr. Kearney: consultant fee/honoraria/speaker's bureau (personal): Boston Scientific Corporation; Abiomed; Cardiovascular Systems, Inc; grant support/research contract (personal) Teleflex. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

With advancements in multicomponent molecular biological tools, the need for versatile, rapid and cost-effective cloning that enables successful combinatorial assembly of DNA plasmids of interest is becoming increasingly important. Unfortunately, current cloning platforms fall short regarding affordability, ease of combinatorial assembly and, above all, the ability to iteratively remove individual cassettes at will. Herein we construct, implement and make available a broad set of cloning vectors, called PlayBack vectors, that allow for the expression of several different constructs simultaneously under separate promoters. Overall, this system is substantially cheaper than other multicomponent cloning systems, has usability for a wide breadth of experimental paradigms and includes the novel feature of being able to selectively remove components of interest at will at any stage of the cloning platform.

Introduction: Patients at high bleeding risk (HBR patients) represent an important subset of patients undergoing percutaneous coronary intervention (PCI). It remains unclear whether a shortened duration of dual antiplatelet therapy (DAPT) confers benefits compared with prolonged duration of DAPT in this patient population. The aim of this study was to investigate and compare bleeding and ischemic outcomes among HBR patients receiving short- versus long-term DAPT after PCI., Methods: A meta-analysis of studies comparing short-term (1-3 months) and long-term (6-12 months) DAPT after PCI with second-generation drug-eluting stents in HBR patients was performed., Results: Six studies [1 randomized controlled trial (RCT), 2 RCT subanalyses, and 3 prospective propensity-matched studies] involving 15,908 patients were included in the meta-analysis. During a follow-up of 12 months, short-term DAPT was associated with a reduction in major bleeding events [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.42-0.95; p = 0.03, I 2  = 71] and comparable definite/probable stent thrombosis, all-cause mortality, cardiovascular mortality, myocardial infarction (MI), and ischemic stroke, compared with long-DAPT. Single antiplatelet therapy (SAPT) with aspirin was comparable to SAPT with P2Y12 inhibitor, with no treatment-by-subgroup interaction for major bleeding events (p-interaction = 0.27). In studies including patients presenting with MI, a trend of more frequent MI was noted in the short-DAPT arm (OR 1.25, 95% CI 0.98-1.59; p = 0.07; I 2  = 0). In a sensitivity analysis comparing 3- and 12-month DAPT, the 3-month DAPT strategy was associated with a higher risk of ischemic stroke (OR 2.37, 95% CI 1.15-4.87; p = 0.02, I 2  = 0%)., Conclusion: Short-term DAPT after PCI in HBR patients was associated a reduction in major bleeding events and similar ischemic outcomes. However, a higher risk of ischemic stroke and MI at 1 year of follow-up was seen in some subsets., (© 2023. The Author(s).)

Background: Data on outcomes of patients with high-risk acute pulmonary embolism (PE) transferred from other hospitals are scarce., Methods: We queried the Nationwide Readmissions Database for admissions who were ≥18 years old, and with a primary discharge diagnosis of acute high-risk PE between the years 2016 and 2019. The main outcome of interest was the difference in all-cause in-hospital mortality between patients admitted directly to small/medium hospitals; patients admitted directly to large hospitals; and patients transferred to large hospitals., Results: Among 11,341 weighted hospitalizations with high-risk PE, 631 (5.6%) patients were transferred to large hospitals. There was no significant change in the rates of transfer during the study period. Transferred patients were younger and had a higher prevalence of comorbidities. They were more likely to present with saddle PE and cor pulmonale and were more likely to receive advanced therapies. In-hospital mortality was not different between patients transferred to large hospitals and those admitted directly to large hospitals (adjusted odd ratio [OR] 1.11, 95% confidence interval [CI] 0.81, 1.54) as well as between patients transferred to large hospitals and those admitted directly to small/medium hospitals (aOR 1.28, 95% CI 0.92, 1.76). The rates of major bleeding and cardiac arrest were higher among transferred patients. Admissions for transferred patients were associated with higher cost and longer length of stay., Conclusion: Transferred patients with high-risk PE were more likely to receive advanced therapies. There was no difference in-hospital mortality rates compared with patients admitted directly to the large or small/medium hospitals., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Aditya S. Bharadwaj reports a relationship with Abiomed Inc. that includes: consulting or advisory and speaking and lecture fees. Aditya S. Bharadwaj reports a relationship with Cardiovascular Solutions Inc. that includes: consulting or advisory and speaking and lecture fees. Aditya S. Bharadwaj reports a relationship with Shockwave Medical Inc. that includes: consulting or advisory and speaking and lecture fees.

Background: Aortic stenosis (AS) is associated with myocardial ischemia through different mechanisms and may impair coronary arterial flow. However, data on the impact of moderate AS in patients with acute myocardial infarction (MI) is limited., Aims: This study aimed to investigate the impact of moderate AS in patients presenting with acute myocardial infarction (MI)., Methods: We conducted a retrospective analysis of all patients who presented with acute MI to all Mayo Clinic hospitals, using the Enterprise Mayo PCI Database from 2005 to 2016. Patients were stratified into two groups: moderate AS and mild/no AS. The primary outcome was all cause mortality., Results: The moderate AS group included 183 (13.3%) patients, and the mild/no AS group included 1190 (86.7%) patients. During hospitalization, there was no difference between both groups in mortality. Patients with moderate AS had higher in-hospital congestive heart failure (CHF) (8.2% vs. 4.4%, p = 0.025) compared with mild/no AS patients. At 1-year follow-up, patients with moderate AS had higher mortality (23.9% vs. 8.1%, p < 0.001) and higher CHF hospitalization (8.3% vs. 3.7%, p = 0.028). In multivariate analysis, moderate AS was associated with higher mortality at 1-year (odds ratio 2.4, 95% confidence interval [1.4-4.1], p = 0.002). In subgroup analyses, moderate AS increased all-cause mortality in STEMI and NSTEMI patients., Conclusion: The presence of moderate AS in acute MI patients was associated with worse clinical outcomes during hospitalization and at 1-year follow-up. These unfavorable outcomes highlight the need for a close follow-up of these patients and for timely therapeutic strategies to best manage these coexisting conditions., (© 2023 Wiley Periodicals LLC.)

Background: Contemporary data comparing the outcomes of transradial access (TRA) vs transfemoral access (TFA) among patients presenting with acute myocardial infarction and cardiogenic shock (AMI-CS) undergoing percutaneous coronary intervention (PCI) are limited., Objectives: This study examines in-hospital outcomes and institutional variation among patients with AMI-CS undergoing TRA-PCI vs TFA-PCI., Methods: Patients admitted with AMI-CS from the NCDR CathPCI registry between April 2018 and June 2021 were included. Multivariable logistic regression and inverse probability weighting models were used to assess the association between access site and in-hospital outcomes. A falsification analysis using non-access site-related bleeding was performed., Results: Among 35,944 patients with AMI-CS undergoing PCI, 25.6% were performed with TRA. The proportion of TRA-PCI increased over the study period (22.0% in the second quarter of 2018 vs 29.1% in the second quarter of 2021; P-trend <0.001). Significant institutional-level variability in the use of TRA-PCI was also observed: 20.9% of all sites using TRA in <2% of PCIs (low utilization) vs 1.9% of all sites using TRA in >80% of PCIs (high utilization). Patients undergoing TRA-PCI had a significantly lower adjusted incidence of major bleeding (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.67-0.76), mortality (OR: 0.73; 95% CI: 0.69-0.78), vascular complications (OR: 0.67; 95% CI: 0.54-0.84), and new dialysis (OR: 0.86; 95% CI: 0.77-0.97). There was no difference in non-access site related bleeding (OR: 0.93; 95% CI: 0.84-1.03). Sensitivity analyses revealed similar benefit with TRA-PCI among patients without arterial cross-over. There were no significant interactions observed between TRA-PCI with mechanical circulatory support and in-hospital outcomes., Conclusions: In this large nationwide contemporary analysis of patients with AMI-CS, about quarter of PCIs were performed via TRA with wide variability across US institutions. TRA-PCI was associated with significantly lower incidence of in-hospital major bleeding, mortality, vascular complications, and new dialysis. This benefit was observed irrespective of mechanical circulatory support use., Competing Interests: Funding Support and Author Disclosures The American College of Cardiology Foundation’s National Cardiovascular Data Registry (NCDR) supported this research. Dr Virani has received grant support from the Department of Veterans Affairs, National Institutes of Health, and Tahir and Jooma Family; and has received an honorarium from the American College of Cardiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Background: Catheter ablation (CA) and left atrial appendage closure (LAAC) require transseptal access; combining both in a single procedure may have advantages. However, the safety of this approach has not been extensively studied. The objective of this study was to compare in hospital outcomes among patients receiving CA, LAAC, and combination of both treatments on the same day., Methods: We conducted a retrospective cohort analysis of the National Inpatient Sample database. The primary outcome was the presence of major adverse cardiovascular and cerebrovascular events (MACCE) during index hospitalization. Secondary outcomes included stroke, pericardial effusion, pericardiocentesis, and bleeding., Results: A total of 69,285 hospitalizations with AF were included in the analysis, of which 71.7% received LAAC, 27.8% received CA, and 0.5% received combination of both treatments on the same day. MACEE (OR, 1.63; 95% CI, 0.39-6.70), stroke (OR, 2.98; 95% CI, 0.55-16.01), pericardial effusion (OR, 0.33; 95% CI, 0.07-1.41), pericardiocentesis (OR, 1.00; 95% CI, 0.25-3.86), and bleeding (OR, 3.25; 95% CI, 0.87-12.07) did not differ significantly between CA and combination treatment. Similarly, MACCE (OR, 1.11; 95% CI, 0.28-4.41), stroke (OR, 1.03; 95% CI, 0.24-4.35), pericardial effusion (OR, 0.45; 95% CI, 0.11-1.90), pericardiocentesis (OR, 0.63; 95% CI, 0.14-2.83), and bleeding (OR, 2.04; 95% CI, 0.65-6.39) did not differ significantly between LAAC and combination treatment., Conclusions: The combined approach is infrequently used in clinical practice (< 1%). However, major life-threatening adverse events did not differ between CA and LAAC when performed in isolation or combined in a single procedural stage on the same day., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Intravascular ultrasound (IVUS) can assist percutaneous coronary intervention (PCI) of chronic total occlusions (CTO)., Methods: We analyzed 8,983 CTO PCIs performed in 8,771 patients between 2012 and 2022 at 39 centers., Results: Overall, IVUS was used in 44.5% of the cases, for crossing in 11.5% and for stent optimization in 33.1%. IVUS for stent optimization was used more often for complex lesions with higher prevalence of calcification (51.2% vs 34.3%; P<.001); was associated with lower air kerma radiation dose (1.78 [1.00, 3.09] vs 2.30 (1.35, 3.91) min, P<.001) and contrast volume (190 [138, 258] vs 220 [160, 300] ml, P<.001). Among cases with successful guidewire crossing, those that used IVUS for stent optimization had higher technical (99.3% vs 96.3%; P<.001) and procedural (96.1% vs 94.6%, P=.002) success rates and similar major adverse complication event rates (2.04% vs 1.62%; P=.176). The use of IVUS for stent optimization significantly increased over time., Conclusion: In a contemporary, multicenter registry, IVUS was used in 44.5% and its use for stent optimization significantly increased over time. Cases where IVUS was used for stent optimization had higher technical and procedural success and similar risk of complications compared with cases where IVUS was not used for stent optimization.

Aims: To examine the shot-term outcomes with catheter-directed thrombolysis (CDT) vs. catheter-directed embolectomy (CDE) for high-risk pulmonary embolism (PE)., Methods and Results: The Nationwide Readmissions Database was utilized to identify hospitalizations with high-risk PE undergoing CDE or CDT from 2016 to 2019. The main outcome was all-cause in-hospital mortality. Propensity score matching was used to compare the outcomes in both groups. Among 3216 high-risk PE hospitalizations undergoing catheter-directed interventions, 868 (27%) received CDE, 1864 (58%) received CDT, and 484 (15%) received both procedures. In the unadjusted analysis, the rate of all-cause in-hospital mortality was not different between CDE and CDT (39.6% vs. 34.2%, P = 0.07). After propensity score matching, there was no difference in the incidence of in-hospital mortality [adjusted odds ratio (aOR): 1.28, 95% confidence interval (CI): 0.95, 1.72, P = 0.10], intracranial haemorrhage (ICH) (adjusted OR 1.57, 95% CI: 0.75, 3.29, P = 0.23), or non-ICH bleeding (aOR: 1.17, 95% CI: 0.85, 1.62, P = 0.33). There were no differences in the length of stay, cost, and 30-day unplanned readmissions between both groups., Conclusion: In this contemporary observational analysis of patients admitted with high-risk PE undergoing CDT or CDE, the rates of in-hospital mortality, ICH, and non-ICH bleeding events were not different., Competing Interests: Conflict of interest: I.W. is a consultant for Magneto Thrombectomy Solutions and PI for Penumbra, Inc. A.S.D. is a consultant and speaker for Abiomed; Cardiovascular Systems, Inc.; and Shockwave. A.W.M. is a consultant and speaker for Boston Scientific., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The left anterior descending artery (LAD) subtends a large myocardial territory. The outcomes of LAD chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have received limited study. We performed a retrospective analysis of all patients who underwent LAD CTO PCI at a high-volume single center. Outcomes included in-hospital and long-term major adverse cardiovascular events (MACEs) and changes in left ventricular ejection fraction (LVEF). We performed a subgroup analysis of patients with ischemic cardiomyopathy, defined as an LVEF of 40% or less. From December 2014 to February 2021, 237 patients underwent LAD CTO PCI. The technical success rate was 97.4%, and the in-hospital MACE rate was 5.4%, A landmark analysis after hospital discharge showed an overall survival of 92% and 85% MACE-free survival at 2 years. There was no difference in overall survival or MACE-free survival between those who had ischemic cardiomyopathy versus those who did not. In patients with ischemic cardiomyopathy, LAD CTO PCI was associated with significant improvement in LVEF (10.9% at 9 months), which was further pronounced when these patients had a proximal LAD CTO and were on optimal medical therapy (14% at 6 months). In a single high-volume center, LAD CTO PCI was associated with 92% overall survival at 2 years, with no difference in survival between patients with or without ischemic cardiomyopathy. LAD CTO PCI was associated with an absolute 10% increase in LVEF at 9 months in patients with ischemic cardiomyopathy., Competing Interests: Disclosures Dr. Alaswad reports as consulting/speaker honoraria from Boston Scientific, Cardiovascular Systems Inc, LivaNova, Teleflex. Dr. Basir reports as consulting/speaker Abbott Vascular, Abiomed, Cardiovascular Systems, Chiesi, Procyrion, Zoll. Dr. Brilakis reports as consulting/speaker honoraria from Abbott Vascular, American Heart Association (associate editor Circulation), Amgen, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), ControlRad, CSI, Ebix, Elsevier, GE Healthcare, InfraRedx, Medtronic, Siemens, and Teleflex; research support from Regeneron and Siemens. Shareholder: MHI Ventures. Dr. Neupane reports as consultant/speaker Boston Scientific, Teleflex, Asahi, Abiomed, CSI, Medtronic, Philips, Shockwave. Dr. Kunkel reports as speaking and consulting fees from Abiomed, CSI, and Shockwave. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Technological and procedural innovations presently permit the safe and effective performance of increasingly complex percutaneous coronary interventions, while new mechanical circulatory support devices offer circulatory and ventricular support to patients with severely reduced left ventricular systolic function and deranged cardiovascular hemodynamics. Together, these advances now permit the application of complex percutaneous coronary interventions to higher-risk patients who might otherwise be left untreated. Increasing observational data support the use of mechanical circulatory support in appropriate complex and high-risk patients as part of a larger multidisciplinary heart team treatment plan. In-progress and upcoming randomized clinical trials may provide higher-quality evidence to better guide management decisions in the near future., Competing Interests: Disclosure: AGT has received consultancy and speakers fees from Abiomed and Shockwave Medical. RD has recevied consultancy and speakers fees from Abiomed, Asahi Intec, Biotronik, Boston Scientific, Medtronic, Siemens Healthcare, and Shockwave Medical. All other authors have no conflicts of interest to declare., (Copyright © The Author(s), 2023. Published by Radcliffe Group Ltd.)

Transcarotid access has emerged as the preferred access site for transcatheter aortic valve implantation (TAVI) in patients with prohibitive iliofemoral anatomy. This study aimed to compare outcomes with transcarotid with those of other accesses in patients who underwent TAVI. Cochrane, EMBASE, and MEDLINE databases were searched for all published studies that compared outcomes with transcarotid with those of other accesses (transfemoral, transaxillary/subclavian, transaortic, and transapical) in patients who underwent TAVI. The primary outcome was all-cause mortality. Secondary outcomes included major bleeding, major vascular complications, stroke, myocardial infarction, permanent pacemaker implantation, and peri-aortic valve insufficiency. We included 22 observational studies with a total of 11,896 patients. Outcomes were reported during hospitalization and at 1-month follow-up. The transcarotid approach had higher mortality at 1 month (3.7% vs 2.6%, p = 0.02) but lower major vascular complications during hospitalization (1.5% vs 3.4%, p = 0.04) than did transfemoral access. The transcarotid approach had lower major vascular complications (2% vs 2.3%, p = 0.04) than did the transaxillary/subclavian but higher major bleeding (5.3% vs 2.6%, p = 0.03). The transaortic approach was associated with higher in-hospital (11.7% vs 1.9%, p = 0.02) and 1-month mortality (14.4% vs 3.9%, p = 0.007) rates than was transcarotid access. The transcarotid approach numerically reduced mortality and the risk of major vascular complications and major bleeding compared with the transapical approach; however, this did not reach statistical significance. The transcarotid approach did not increase the risk of stroke compared with transfemoral or the other alternative accesses. In conclusion, the transcarotid or transaxillary/subclavian approach had associated comparable outcomes that were better than those of the transapical and transaortic approaches. There was no difference in stroke risk between transcarotid access and other accesses., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is associated with a considerable risk of complications, and risk stratification is of utmost importance., Aims: To assess the clinical usefulness of the recently developed PROGRESS-CTO (NCT02061436) complication risk scores in an independent cohort., Methods: Individual patient data pooled analysis of 3 registries was performed., Results: Of the 4569 patients who underwent CTO PCI, 102 (2.2%) had major adverse cardiovascular events (MACE). Patients with MACE were older (69 ± 11 vs. 65 ± 10, p < 0.001), more likely to have a history of prior coronary artery bypass graft surgery, and unfavorable angiographic characteristics J-CTO score (2.4 ± 1.2 vs. 2.1 ± 1.3, p = 0.007), including blunt stump (59% vs. 49%, p = 0.047). Technical success was lower in patients with MACE (59% vs. 86%, p < 0.001). The area under the receiver operating characteristic curve of the PROGRESS-CTO complication risk models were as follows: MACE 0.72 (95% confidence interval [CI], 0.67-0.76), mortality 0.73 (95% CI, 0.61-0.85), and pericardiocentesis 0.69 (95% CI, 0.62-0.77) in the validation dataset. The observed complication rates increased with higher PROGRESS-CTO complication scores. The PROGRESS-CTO MACE score showed good calibration in this external cohort, with MACE rates similar to the original study: 0.7% (score 0-1), 1.5% (score 2), 2.2% (score 3), 3.8% (score 4), 4.9% (score 5), 5.8% (score 6-7)., Conclusion: Given the good discriminative performance, calibration, and ease of calculation, the PROGRESS-CTO complication scores could help assess the risk of complications in patients undergoing CTO PCI., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Studies comparing plug-based (i.e., MANTA) with suture-based (i.e., ProStar XL and ProGlide) vascular closure devices (VCDs) for large-bore access closure after transcatheter aortic valve replacement (TAVR) have yielded mixed results., Aims: To examine the comparative safety and efficacy of both types of VCDs among TAVR recipients., Methods: An electronic database search was performed through March 2022 for studies comparing access-site related vascular complications with plug-based versus suture-based VCDs for large-bore access site closure after transfemoral (TF) TAVR., Results: Ten studies (2 randomized controlled trials [RCTs] and 8 observational studies) with 3113 patients (MANTA = 1358, ProGlide/ProStar XL = 1755) were included. There was no difference between plug-based and suture-based VCD in the incidence of access-site major vascular complications (3.1% vs. 3.3%, odds ratio [OR]: 0.89; 95% confidence interval [CI]: 0.52-1.53). The incidence of VCD failure was lower in plug-based VCD (5.2% vs. 7.1%, OR: 0.64; 95% CI: 0.44-0.91). There was a trend toward a higher incidence of unplanned vascular intervention in plug-based VCD (8.2% vs. 5.9%, OR: 1.35; 95% CI: 0.97-1.89). Length of stay was shorter with MANTA. Subgroup analyses suggested significant interaction based on study designs such that there was higher incidence of access-site vascular complications and bleeding events with plug-based versus suture-based VCD among RCTs., Conclusion: In patients undergoing TF-TAVR, large-bore access site closure with plug-based VCD was associated with a similar safety profile as suture-based VCD. However, subgroup analysis showed that plug-based VCD was associated with higher incidence of vascular and bleeding complications in RCTs., (© 2023 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: TandemHeart has been demonstrated to improve hemodynamic and metabolic complications in cardiogenic shock (CS). Contemporary outcomes have not been reported., Objectives: To evaluate the outcomes of the TandemHeart (LivaNova) in contemporary real-world use., Methods: We analyzed baseline characteristics, hemodynamic changes, and outcomes of all patients treated with TandemHeart who were enrolled in the THEME registry, a multicenter, prospective, observational study., Results: Between May 2015 and June 2019, 50 patients underwent implantation of the TandemHeart device. 22% of patients had TandemHeart implanted within 12 h, 32% within 24 h, and 52% within 48 h of CS diagnosis. Cardiac index (CI) was significantly improved 24 h after implantation (median change 1.0, interquartile range (IQR) (0.5-1.4 L/min/m 2 ). In survivors, there was a significant improvement in CI (1.0, IQR (0.5-2.25 L/min/m 2 ) and lactate clearance -2.3 (-5.0 to -0.7 mmol/L). The 30-day and 180-day survival were 74% (95% confidence interval: 60%-85%) and 66% (95% confidence interval: 51%-79%), respectively. Survival was similarly high in those in whom TandemHeart has been used as a bridge to surgery (85% 180-day survival)., Conclusion: In a contemporary cohort of patients presenting in CS, the use of TandemHeart is associated with a 74% 30-day survival and a 66% 180-day survival., (© 2023 Wiley Periodicals LLC.)

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., (© 2023 Wiley Periodicals LLC.)

Objectives: The study objectives were to describe the trends and outcomes of isolated coronary artery bypass grafting after ST-elevation myocardial infarction using a nationwide database., Methods: We queried the 2002-2016 National Inpatient Sample database for hospitalized patients with ST-elevation myocardial infarction who underwent isolated coronary artery bypass grafting. We report temporal trends, predictors, and outcomes of coronary artery bypass grafting in the early (2002-2010) and recent (2011-2016) cohorts., Results: Of 3,347,470 patients hospitalized for ST-elevation myocardial infarction, 7.7% underwent isolated coronary artery bypass grafting. The incidence of isolated coronary artery bypass grafting after ST-elevation myocardial infarction decreased over time (9.2% in 2002 vs 5.5% in 2016, P trend  < .001), whereas perioperative crude in-hospital mortality did not change (5.1% in 2002 vs 4.2% in 2016, P trend  = .66), coinciding with an increase in the burden of comorbidities. There was an increase in performing isolated coronary artery bypass grafting on hospitalization day 3 or more, as well as an increase in the use of mechanical support devices and precoronary artery bypass grafting percutaneous coronary intervention. In the early cohort, isolated coronary artery bypass grafting on days 1 and 2 was associated with higher in-hospital mortality. In the recent cohort, coronary artery bypass grafting on day 2 had similar in-hospital mortality compared with day 3 or more and lower rates of acute kidney injury, ischemic stroke, ventricular arrhythmia, and length of hospital stay., Conclusions: In this nationwide analysis, there has been a decline in the use of isolated coronary artery bypass grafting after ST-elevation myocardial infarction. Isolated coronary artery bypass grafting on day 1 was performed in sicker patients and was associated with higher in-hospital mortality than coronary artery bypass grafting performed on day 3 or more. In the recent cohort, isolated coronary artery bypass grafting on day 2 had similar in-hospital mortality compared with day 3 or more., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery perforation is one of the most feared and common complications of chronic total occlusion (CTO) percutaneous coronary intervention (PCI)., Methods: To assess the usefulness of the recently developed PROGRESS-CTO (NCT02061436) perforation risk score in independent cohorts. Individual patient-level data pooled analysis of three registries was performed., Results: Of the 4566 patients who underwent CTO PCI at 25 centers, 196 (4.2%) had coronary artery perforation. Patients with perforations were older (69 ± 10 vs. 65 ± 10, p < 0.001), more likely to be women (19% vs. 13%, p = 0.009), more likely to have a history of prior coronary artery bypass graft (34% vs. 20%, p < 0.001), and unfavorable angiographic characteristics such as blunt stump (62% vs. 48%, p < 0.001), proximal cap ambiguity (52% vs. 34%, p < 0.001), and moderate-severe calcification (60% vs. 49%, p = 0.002). Technical success was lower in patients with perforations (73% vs. 88%, p < 0.001). The area under the receiver operating characteristic curve of the PROGRESS-CTO perforation risk model was 0.76 (95% confidence interval [CI], 0.72-0.79), with good calibration (Hosmer-Lemeshow p = 0.97). We found that the CTO PCI perforation risk increased with higher PROGRESS-CTO perforation scores: 0.3% (score 0), 2.3% (score 1), 3.1% (score 2), 5.5% (score 3), 7.5% (score 4), 14.6% (score 5)., Conclusion: Given the good discriminative performance, calibration, and the ease of calculation, the PROGRESS-CTO perforation score may facilitate assessment of the risk of perforation in patients undergoing CTO PCI., (© 2023 Wiley Periodicals LLC.)

Management of non-ST elevation myocardial infarction (NSTEMI) has evolved over the years, but most published data are from younger patients. Data on the NSTEMI management in older patients remain limited. We performed a meta-analysis of randomized controlled trials to evaluate the long-term outcomes of invasive versus conservative strategies in older patients (>70 years old) with NSTEMI. Of 1,550 reports searched, 4 randomized controlled trials (1,126 patients) were included in the analysis, with a median follow-up of 1.25 years (range: 1 to 2.5 years). The median age of included patients was 83.6 (interquartile range: 2.8 years). The invasive strategy was associated with significantly lower risk of major adverse cardiac and cerebrovascular event (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.40 to 0.91, I 2  = 54%; 3 trials] and unplanned revascularization (OR 0.31, 95% CI 0.15 to 0.64, I 2  = 1.7%; 3 trials] than was the conservative strategy. There was no difference in all-cause mortality (OR 0.88, 95% CI 0.65 to 1.18, I 2  = 0%; 4 trials], myocardial infarction (OR 0.70, 95% CI 0.42 to 1.19, I 2  = 54.7%; 4 trials], or bleeding (OR 0.87, 95% CI 0.39 to 1.93, I 2  = 0%; 3 trials] between the strategies. In conclusion, the use of initial invasive strategy in older patients presenting with NSTEMI was associated with a significantly lower risk of major adverse cardiac and cerebrovascular event and unplanned revascularization than that of the initial conservative strategy without increased bleeding., (Copyright © 2022 Elsevier Inc. All rights reserved.)

There is a paucity of data on the contemporary use of non-drug-eluting devices (balloon angioplasty or bare-metal stents) in contemporary percutaneous coronary intervention (PCI) in the United States. We utilized the Nationwide Readmissions Database to identify patients hospitalized to undergo PCI with non-drug-eluting devices from 2016 to 2019. The main outcome of interest was the trends in utilization over the study years. Among 1,870,262 PCI procedures, 127,810 (6.8%) were performed with non-drug-eluting devices; 72% of these were in the setting of acute myocardial infarction (MI). The use of non-drug-eluting devices decreased throughout the study period from 12.9% of all PCI in the first quarter of 2016 to 3.4% in the last quarter of 2019 (p <0.001). Factors associated with their use included advanced age and high bleeding risk. Only a small percentage were used as a bridge to coronary artery bypass graft surgery (2%) and for treatment of in-stent restenosis (3%). The in-hospital mortality was 5.8% for the entire cohort and 6.6% when the indication for use was an acute MI. In patients presenting with an acute MI, reinfarction within 30 days was common and occurred in 18% of the patients. In conclusion, the use of non-drug-eluting devices in PCI in the United States decreased from 2016 to 2019. Factors associated with their use included old age and high bleeding risk. Due to suboptimal outcomes in patients currently being treated with non-drug-eluting devices, there remains an unmet clinical need for alternative treatment options., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Whether saphenous vein grafts (SVGs) should be occluded after successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) of the corresponding native vessel remains controversial., Methods: We analyzed the clinical and angiographic characteristics and procedural outcomes of 51 patients who underwent SVG occlusion following successful CTO-PCI of the corresponding native vessel between 2015 and 2022 at 14 centers., Results: Mean patient age was 71 ± 8 years and 80% were men. The most common CTO target vessel was the right coronary artery (41%), followed by the left circumflex (37%). Retrograde crossing through the SVG was the successful crossing strategy in 40 cases (78%). SVG occlusion was achieved with coils (1.9 ± 1.0) in 35 of 51 patients (69%) and vascular plugs in the other 16 cases (31%). All procedures were technically successful and the SVG was occluded completely (TIMI 0 flow) in 38 of the cases (75%), with the remaining cases having TIMI 1 flow. Follow-up was available for 37 patients (73%); during a mean follow-up of 312 days from CTO-PCI, the incidence of target-lesion failure due to restenosis was 5.4% (n = 2) with no other major events reported., Conclusion: Following native vessel CTO-PCI, SVG occlusion is often performed and is associated with favorable mid-term outcomes.

Objectives: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can improve patient symptoms, but it remains controversial whether it impacts subsequent clinical outcomes., Methods: In this systematic review and meta-analysis, we queried PubMed, ScienceDirect, Cochrane Library, Web of Science, and Embase databases (last search: September 15, 2021). We investigated the impact of CTO-PCI on clinical events including all-cause mortality, cardiovascular death, myocardial infarction (MI), major adverse cardiovascular event (MACE), stroke, subsequent coronary artery bypass surgery, target-vessel revascularization, and heart failure hospitalizations. Pooled analysis was performed using a random-effects model., Results: A total of 58 publications with 54,540 patients were included in this analysis, of which 33 were observational studies of successful vs failed CTO-PCI, 19 were observational studies of CTO-PCI vs no CTO-PCI, and 6 were randomized controlled trials (RCTs). In observational studies, but not RCTs, CTO-PCI was associated with better clinical outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) for all-cause mortality, MACE, and MI were 0.52 (95% CI, 0.42-0.64), 0.46 (95% CI, 0.37-0.58), 0.66 (95% CI, 0.50-0.86), respectively for successful vs failed CTO-PCI studies; 0.38 (95% CI, 0.31-0.45), 0.57 (95% CI, 0.42-0.78), 0.65 (95% CI, 0.42-0.99), respectively, for observational studies of CTO-PCI vs no CTO-PCI; 0.72 (95% CI, 0.39-1.32), 0.69 (95% CI, 0.38-1.25), and 1.04 (95% CI, 0.46-2.37), respectively for RCTs., Conclusions: CTO-PCI is associated with better subsequent clinical outcomes in observational studies but not in RCTs. Appropriately powered RCTs are needed to conclusively determine the impact of CTO-PCI on clinical outcomes.

Objective: To compare the clinical outcomes after extraplaque (EP) versus intraplaque (IP) tracking in chronic total occlusion (CTO) percutaneous coronary intervention (PCI)., Background: The impact of modern dissection and reentry (DR) techniques on the long-term outcomes of CTO PCI remains controversial., Methods: We performed a systematic review and meta-analysis of studies that compared EP versus IP tracking in CTO PCI. Odds ratios (ORs) with 95% confidence intervals (CIs) are calculated using the Der-Simonian and Laird random-effects method., Results: Our meta-analysis included seven observational studies with 2982 patients. Patients who underwent EP tracking had significantly more complex CTOs with higher J-CTO score, longer lesion length, and more severe calcification and had significantly longer stented segments. During a median follow-up of 12 months (range 9-12 months), EP tracking was associated with a higher risk of major adverse cardiovascular events (MACE) (OR 1.50, 95% CI (1.10-2.06), p = 0.01) and target vessel revascularization (TVR) (OR 1.69, 95% CI (1.15-2.48), p = 0.01) compared with IP tracking. There was no difference in the incidence of all-cause death (OR 1.37, 95% CI (0.67-2.78), p = 0.39), myocardial infarction (MI) (OR 1.48, 95% CI (0.82-2.69), p = 0.20), stent thrombosis (OR 2.09, 95% CI (0.69-6.33), p = 0.19), or cardiac death (OR 1.10, 95% CI (0.39-3.15), p = 0.85) between IP and EP tracking., Conclusion: EP tracking is utilized in more complex CTOs and requires more stents. EP tracking is associated with a higher risk of MACE, driven by a higher risk of TVR at 1 year, but without an increased risk of death or MI compared with IP tracking. EP tracking is critically important for contemporary CTO PCI., (© 2022 Wiley Periodicals LLC.)

Background: There are limited data describing gender differences in patients undergoing chronic total occlusion (CTO) percutaneous coronary interventions (PCI)., Methods: We compared baseline clinical and angiographic characteristics and procedural outcomes between men and women among 9457 CTO PCIs performed at 38 centers between 2012 and 2022., Results: A total of 7687 (81%) men and 1770 (19%) women were treated. Women were older, more likely to have comorbidities such as diabetes, hypertension and peripheral arterial disease, and had higher left ventricular ejection fraction. The most common CTO target vessel was the right coronary artery for both men (53%) and women (52%), although the left anterior descending artery was more frequently the target vessel among women (31% vs. 25%; p < 0.001). The J-CTO score (2.4 ± 1.3 vs. 2.2 ± 1.2; p < 0.001) as well as the PROGRESS-CTO score (1.3 ± 1.0 vs. 1.1 ± 1.0; p < 0.001) were higher among men. In female patients, antegrade wiring was more frequently the initial crossing strategy (87.6% vs. 82.4%; p < 0.001) and was more successful in crossing the target lesion (62.7% vs. 54.0%; p < 0.001) compared with men. Interventions in men required longer procedure time and fluoroscopy time, as well as higher air kerma radiation dose and contrast volume when compared to women. Technical (89% vs. 86%; p < 0.001) and procedural (87% vs. 84%; p = 0.003) success rates were higher among women. In-hospital major adverse cardiovascular events (MACE) were also higher in women (2.9% vs. 1.8%; p < 0.001)., Conclusions: Women undergoing CTO PCI had higher technical and procedural success rates, but also higher in-hospital MACE compared with men., (© 2022 Wiley Periodicals LLC.)

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., (© 2022 Wiley Periodicals LLC.)

Objective: To examine the sex differences in management and outcomes among patients with high-risk acute pulmonary embolism (PE)., Patients and Methods: The Nationwide Readmissions Database was used to identify hospitalizations with high-risk PE from January 1, 2016, to December 31, 2018. Differences in use of advanced therapies, in-hospital mortality, and bleeding events were compared between men and women., Results: A total of 125,901 weighted hospitalizations with high-risk PE were identified during the study period; 46.3% were women (n=58,253). Women were older and had a higher prevalence of several comorbidities and risk factors of PE such as morbid obesity, diabetes mellitus, chronic pulmonary disease, heart failure, and metastatic cancer. Systemic thrombolysis and catheter-directed interventions were more commonly used among women; however, mechanical circulatory support was less frequently used. In-hospital mortality was higher among women in the unadjusted analysis (30.7% vs 27.8%, P<.001) and after propensity score matching (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.08 to 1.25; P<.001), whereas the rates of intracranial hemorrhage and non-intracranial hemorrhage were not different. On multivariate regression analysis, female sex (OR, 1.18; 95% CI, 1.15 to 1.21; P<.001) was independently associated with increased odds of in-hospital mortality., Conclusion: In this contemporary observational cohort of patients admitted with high-risk PE, women had higher rates of in-hospital mortality despite receiving advanced therapies more frequently, whereas the rate of major bleeding events was not different from men. Efforts are needed to minimize the excess mortality observed among women., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aims: There is limited data on the association between hospital catheter-directed intervention (CDI) volume and outcomes among patients with acute pulmonary embolism (PE)., Methods and Results: The Nationwide Readmissions Database years 2016-2019 was utilized to identify hospitalizations undergoing CDI for acute PE. Hospitals were divided into tertiles based on annual CDI volume; low-volume (1-3 procedures), moderate-volume (4-12 procedures) and high-volume (>12 procedures). The primary outcome was all-cause in-hospital mortality. Among 1 436 382 PE admissions, 2.6% underwent CDI; 5.6% were in low-volume, 17.3% in moderate-volume and 77.1% in high-volume hospitals. There was an inverse relationship between hospital CDI volume and in-hospital mortality (coefficient  -0.344, P < 0.001). On multivariable regression analysis, hospitals with high CDI volume were associated with lower in-hospital mortality compared with hospitals with low CDI volume (adjusted odds ratio [OR] 0.71; 95% confidence interval [CI] 0.53, 0.95). Additionally, there was an inverse association between CDI volume and length of stay (LOS) (regression coefficient -0.023, 95% CI -0.027, -0.019) and cost (regression coefficient -74.6, 95% CI -98.8, -50.3). There were no differences in major bleeding and 30-day unplanned readmission rates between the three groups., Conclusion: In this contemporary observational analysis of PE admissions undergoing CDI, there was an inverse association between hospital CDI volume and in-hospital mortality, LOS, and cost. Major bleeding and 30-day unplanned readmission rates were similar between the three groups., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Data on myocardial infarction (MI) treatment in patients with previous coronary artery bypass grafting (CABG) is limited. We queried the Nationwide Readmissions Database to identify hospitalizations of patients with MI from 2016 to 2019. Among hospitalized patients presenting with MI, 10.3% had previous CABG. Patients with MI who had previous CABG were less likely to be revascularized than those without previous CABG for both ST-segment elevation MI (STEMI) (46.4% vs 68.4%) and non-ST-segment elevation MI (NSTEMI) (30.8% vs 36.7%). CABG was associated with a lower risk of death in NSTEMI patients (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.82 to 0.86), but a higher risk in STEMI patients (OR 1.06, 95% CI 1.01 to 1.13). Revascularization was associated with a lower risk of in-hospital death in patients with previous CABG presenting with STEMI (OR 0.30, 95% CI 0.26 to 0.35) and NSTEMI (OR 0.21, 95% CI 0.19 to 0.23)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Retinoic acid, the active metabolite of Vitamin A, is important for the appropriate development of the nervous system (e.g., neurite outgrowth) as well as for cognition (e.g., memory formation) in the adult brain. We have shown that many of the effects of retinoids are conserved in the CNS of the mollusc, Lymnaea stagnalis . RXRs are predominantly nuclear receptors, but the Lymnaea RXR (LymRXR) exhibits a non-nuclear distribution in the adult CNS, where it is also implicated in non-genomic retinoid functions. As such, we developed a CNS Drosophila organ culture-based system to examine the transcriptional activity and ligand-binding properties of LymRXR, in the context of a live invertebrate nervous system. The novel ligand sensor system was capable of reporting both the expression and transcriptional activity of the sensor. Our results indicate that the LymRXR ligand sensor mediated transcription following activation by both 9- cis RA (the high affinity ligand for vertebrate RXRs) as well as the vertebrate RXR synthetic agonist, SR11237. The LymRXR ligand sensor was also activated by all- trans RA, and to a much lesser extent by the vertebrate RAR synthetic agonist, EC23. This sensor also detected endogenous retinoid-like activity in the CNS of developing Drosophila larvae, primarily during the 3 rd instar larval stage. These data indicate that the LymRXR sensor can be utilized not only for characterization of ligand activation for studies related to the Lymnaea CNS, but also for future studies of retinoids and their functions in Drosophila development.

Contemporary data on the national trends in pulmonary embolism (PE) admissions and outcomes are scarce. We aimed to analyze trends in mortality and different treatment methods in acute PE. We queried the Nationwide Readmissions Database (2016 to 2019) to identify hospitalizations with acute PE using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. We described the national trends in admissions, in-hospital mortality, readmissions, and different treatment methods in acute PE. We identified 1,427,491 hospitalizations with acute PE, 2.4% of them (n = 34,446) were admissions with high-risk PE. The rate of in-hospital mortality in all PE hospitalizations was 6.5%, and it remained unchanged throughout the study period. However, the rate of in-hospital mortality in high-risk PE decreased from 48.1% in the first quarter of 2016 to 38.9% in the last quarter of 2019 (p-trend <0.001). The rate of urgent 30-day readmission was 15.2% in all PE admissions and 19.1% in high-risk PE admissions. In all PE admissions, catheter-directed interventions (CDI) were used more often (2.5%) than systemic thrombolysis (ST) (2.1%). However, in admissions with high-risk PE, ST remained the most frequently used method (ST vs CDI: 11.3% vs 6.6%). In conclusion, this study showed that the rate of in-hospital mortality in high-risk PE decreased from 2016 to 2019. ST was the most frequently used method for achieving pulmonary reperfusion in high-risk PE, whereas CDI was the most frequently used method in the entire PE cohort. In-hospital death and urgent readmissions rates remain significantly high in patients with high-risk PE., Competing Interests: Disclosures Dr. Sanjog Kalra is a consultant and Speakers’ bureau and/or Advisory Board participant for Boston Scientific, Cardiovascular Systems Inc, Translumina Therapeutics, Abiomed Inc., and Philips Healthcare. Dr. Wissam Jaber receives consultation fees and research grants from Inari Medical. All other authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)