Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock.

BACKGROUND: Cardiogenic shock is associated with substantial morbidity and mortality. Although inotropic support is a mainstay of medical therapy for cardiogenic shock, little evidence exists to guide the selection of inotropic agents in clinical practice. METHODS: We randomly assigned patients with cardiogenic shock to receive milrinone or dobutamine in a double-blind fashion. The primary outcome was a composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke diagnosed by a neurologist, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite outcome. RESULTS: A total of 192 participants (96 in each group) were enrolled. The treatment groups did not differ significantly with respect to the primary outcome; a primary outcome event occurred in 47 participants (49%) in the milrinone group and in 52 participants (54%) in the dobutamine group (relative risk, 0.90; 95% confidence interval [CI], 0.69 to 1.19; P = 0.47). There were also no significant differences between the groups with respect to secondary outcomes, including in-hospital death (37% and 43% of the participants, respectively; relative risk, 0.85; 95% CI, 0.60 to 1.21), resuscitated cardiac arrest (7% and 9%; hazard ratio, 0.78; 95% CI, 0.29 to 2.07), receipt of mechanical circulatory support (12% and 15%; hazard ratio, 0.78; 95% CI, 0.36 to 1.71), or initiation of renal replacement therapy (22% and 17%; hazard ratio, 1.39; 95% CI, 0.73 to 2.67). CONCLUSIONS: In patients with cardiogenic shock, no significant difference between milrinone and dobutamine was found with respect to the primary composite outcome or important secondary outcomes. (Funded by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario; ClinicalTrials.gov number, NCT03207165.).

Impact of intracoronary assessments on revascularization decisions: A contemporary evaluation.

OBJECTIVES: To investigate the real-world implementation of intracoronary assessment (ICA) techniques and evaluate their impact on clinical decisions regarding the management of coronary artery disease (CAD) in contemporary practice. BACKGROUND: Coronary angiogram is the gold standard used to diagnose vessel stenosis and guide percutaneous coronary intervention (PCI); however, it is limited by its two-dimensional imaging capabilities. ICA techniques like intravascular ultrasound and optical coherence tomography capture the vessel in three-dimensional images. Comparatively, fractional flow reserve provides information on the physiologic significance of coronary stenosis. Both techniques may improve PCI outcomes if they routinely change physician behavior. METHODS: Patients who underwent ICA between August 2015 and March 2020 were included in the study. The primary outcome was the clinical impact of ICA on physician clinical decision making of a stenotic vessel. The secondary outcome was the clinical changes that occurred following ICA. RESULTS: A total of 1135 patients were included in the study. Physiologic assessment (PA) and image assessment (IA) were performed in 61.4% and 38.6% respectively. Management plans were changed in 38.1% and 23.9% of patients who received PA and IA. Over half of the management change resulted in physicians deciding to not intervene on the stenotic vessel. One-year outcome of these decisions showed no significant increase in major adverse cardiac events (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.40-1.15; p = 0.15) or unplanned revascularization (HR, 0.78; 95% CI, 0.35-1.74; p = 0.55) suggesting reliance on PA/IA data did not increase risk. CONCLUSION: Selected ICA alters physician management of CAD in one-third of patients being evaluated for revascularization-typically leading to fewer interventions. All cause death is numerally lower in patients that received a change in management. However, the 1-year outcome of these altered decisions does not appear to be significantly different.

Acute kidney injury after radial or femoral artery access in ST-segment elevation myocardial infarction: AKI-SAFARI.

BACKGROUND: Acute kidney injury (AKI) complicating primary percutaneous coronary intervention (PCI) is an independent predictor of short- and long-term outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). Prior studies suggest a lower incidence of AKI in patients undergoing PCI through radial artery compared to femoral artery access; however, no randomized clinical trials have specifically investigated this question in patients presenting with STEMI. METHODS: To determine whether radial access (RA) is associated with a reduced frequency of AKI following primary PCI, we performed a substudy of the SAFARI-STEMI trial. The SAFARI-STEMI trial was an open-label, multicenter trial, which randomized patients presenting with STEMI to RA or femoral access (FA), between July 2011 and December 2018. The primary outcome of this post hoc analysis was the incidence of AKI, defined as an absolute (>0.5 mg/dL) or relative (>25%) increase in serum creatinine from baseline. RESULTS: In total 2,285 (99.3%) of the patients enrolled in SAFARI-STEMI were included in the analysis-1,132 RA and 1,153 FA. AKI occurred in 243 (21.5%) RA patients and 226 (19.6%) FA patients (RR: 0.91, 95% CI: 0.78-1.07, P = .27). An absolute increase in serum creatinine >0.5 mg/dL was seen in 49 (4.3%) radial and 52 (4.5%) femoral patients (RR: 1.04, 95% CI: 0.71-1.53, P = .83). AKI was lower in both groups when the KDIGO definition was applied (RA 11.9% vs FA 10.8%; RR: 0.90, 95% CI: 0.72-1.13, P = .38). CONCLUSIONS: Among STEMI patients enrolled in the SAFARI-STEMI trial, there was no association between catheterization access site and AKI, irrespective of the definition applied. These results challenge the independent association between catheterization access site and AKI noted in prior investigations.

Effect of Moderate vs Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The CAPITAL CHILL Randomized Clinical Trial.

Importance: Comatose survivors of out-of-hospital cardiac arrest experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 °C to 36 °C for 24 hours. However, small studies suggest a potential benefit of targeting lower body temperatures. Objective: To determine whether moderate hypothermia (31 °C), compared with mild hypothermia (34 °C), improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest. Design, Setting, and Participants: Single-center, double-blind, randomized, clinical superiority trial carried out in a tertiary cardiac care center in eastern Ontario, Canada. A total of 389 patients with out-of-hospital cardiac arrest were enrolled between August 4, 2013, and March 20, 2020, with final follow-up on October 15, 2020. Interventions: Patients were randomly assigned to temperature management with a target body temperature of 31 °C (n = 193) or 34 °C (n = 196) for a period of 24 hours. Main Outcomes and Measures: The primary outcome was all-cause mortality or poor neurologic outcome at 180 days. Neurologic outcome was assessed using the Disability Rating Scale, with poor neurologic outcome defined as a score greater than 5 (range, 0-29, with 29 being the worst outcome [vegetative state]). There were 19 secondary outcomes, including mortality at 180 days and length of stay in the intensive care unit. Results: Among 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial. The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 °C group and in 83 of 183 patients (45.4%) in the 34 °C group (risk difference, 3.0% [95% CI, 7.2%-13.2%]; relative risk, 1.07 [95% CI, 0.86-1.33]; P = .56). Of the 19 secondary outcomes, 18 were not statistically significant. Mortality at 180 days was 43.5% and 41.0% in patients treated with a target temperature of 31 °C and 34 °C, respectively (P = .63). The median length of stay in the intensive care unit was longer in the 31 °C group (10 vs 7 days; P = .004). Among adverse events in the 31 °C group vs the 34 °C group, deep vein thrombosis occurred in 11.4% vs 10.9% and thrombus in the inferior vena cava occurred in 3.8% and 7.7%, respectively. Conclusions and Relevance: In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 °C. However, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02011568.

In-hospital outcomes of STEMI patients on warfarin undergoing primary PCI.

OBJECTIVES: We sought to describe the safety and efficacy outcomes of patients on warfarin presenting with ST-elevation myocardial infarction (STEMI). BACKGROUND: Limited data exist on the outcomes and optimal management of STEMI patients on warfarin undergoing primary percutaneous coronary intervention (PCI). METHODS: Baseline characteristics and outcomes were prospectively collected for 2,390 consecutive STEMI patients referred for primary PCI. Patients were stratified based on warfarin use at baseline. The primary safety endpoint was the rate of in-hospital bleeding (a composite of major bleeding or minor bleeding) according to the thrombolysis in myocardial infarction (TIMI) classification. Efficacy endpoints included major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, as well as intracranial bleeding, cardiogenic shock, and length of stay. Multiple logistic regression was used to determine if warfarin was independently associated with bleeding and MACE. RESULTS: Warfarin patients (n = 59 vs. n = 2,331) were significantly older (73.2 years vs. 61.7 years; P < 0.01), and more likely to present as Killip Class IV (13.6% vs. 2.7%; P < 0.01). TIMI major/minor bleeding occurred in 30.4% of the warfarin patients and 14.2% of the control patients (P < 0.01). After adjustment warfarin was independently associated with an increased risk of bleeding (OR 2.08; P = 0.04). Warfarin patients also had an increased frequency of MACE (20.3% vs. 5.9%; P < 0.01), though this was not significant after adjustment (OR 2.00; P = 0.10). CONCLUSIONS: STEMI patients on warfarin referred for primary PCI are more likely to experience bleeding. New strategies are needed to optimize the management and minimize bleeding in this high-risk population.

Incidence, predictors, and clinical outcomes of early stent thrombosis in acute myocardial infarction patients treated with primary percutaneous coronary angioplasty (insights from the University of Ottawa Heart Institute STEMI registry).

BACKGROUND: Early stent thrombosis (ST) remains an important complication of primary percutaneous intervention (PCI). To date, our information on angiographic and clinical predictors of early ST in ST-segment elevation myocardial infarction (STEMI) patients treated with primary PCI is limited. METHODS: We tried to evaluate the incidence, predictors, and outcomes of early ST in real-world patients treated with primary PCI. We identified all the patients presenting with STEMI between June 2004 and January 2011 who underwent primary PCI as the primary mode of revascularization. Diagnosis of ST was made as per the standard definition proposed by the Academic Research Consortium. RESULTS: The incidence of early ST was 1% among 2,303 patients treated with primary PCI. Definite and probable early ST occurred in 22 and 2 patients, respectively. Patients with early ST had higher in-hospital (P = 0.03) and 30-day mortality (P = 0.048). The rate of cardiogenic shock (P = 0.0006) and cerebrovascular accident (P = 0.0004) was also greater in the early ST group. Smaller stent diameter and lower use of intracoronary glycoprotein IIb/IIIa inhibitor were associated with higher rate of early ST. There was a trend of higher bivalirudin use in ST group, which did not reach significance (P = 0.07) On IVUS imaging, stent malapposition and uncovered plaque area were noted in 6 out of 11 cases. CONCLUSION: The incidence of early ST in primary PCI cohort is low. However, it is still associated with higher mortality and morbidity. Small stent diameter and disuse of intracoronary glycoprotein IIb/IIIa inhibitor may be associated with early ST.

Transcatheter Aortic Valve Implantation (TAVI) for Native Aortic Valve Regurgitation　- A Systematic Review.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become the standard of care for management of high-risk patients with aortic stenosis. Limited data is available regarding the performance of TAVI in patients with native aortic valve regurgitation (NAVR).Methods and Results:We performed a systematic review from 2002 to 2016. The primary outcome was device success as per VARC-2 criteria. Secondary endpoints included procedural complications, and 30-day and 1-year mortality rates. A total of 175 patients were included from 31 studies. Device success was reported in 86.3% of patients - with device failure driven by moderate aortic regurgitation (AR ≥3+) and/or need for a second device. Procedural complications were rare, with no procedural deaths, myocardial infarctions or annular ruptures reported. Procedural safety was acceptable with a low 30-day incidence of stroke (1.5%). The 30-day and 1-year overall mortality rates were 9.6% and 20.0% (cardiovascular death, 3.8% and 10.1%, respectively). Patients receiving 2nd-generation valves demonstrated similar safety profiles with greater device success compared with 1st-generation valves (96.2% vs. 78.4%). This was driven by the higher incidence of second-valve implantation (23.4% vs. 1.7%) and significant paravalvular leak (8.3% vs. 0.0%). CONCLUSIONS: TAVI demonstrates acceptable safety and efficacy in high-risk patients with severe NAVR. Second-generation valves may afford a similar safety profile with improved device success. Dedicated studies are needed to definitively establish the efficacy of TAVI in this population.

The impact of switching P2Y12 receptor inhibitor therapy during index hospitalization: a systematic review.

PURPOSE: With the availability of novel P2Y12 receptor inhibitors, patients presenting with acute coronary syndrome (ACS) may receive more than one type of this drug during index hospitalization. We sought to determine the effect of switching from clopidogrel to a novel P2Y12 receptor inhibitor on the occurrence of major adverse cardiovascular events (MACE) and bleeding. METHODS: We conducted a literature search on SCOPUS for English language entries until 7 March 2015. Out of 188 citations, seven studies encompassing 16,431 patients were selected for analysis of (i) switching to a novel P2Y12 agent (switching group) versus continued clopidogrel or (ii) switching to a novel P2Y12 agent (switching group) versus upfront novel agent initiation during index hospitalization RESULTS: MACE was significantly lower in the switching group (odds ratio (OR) 0.77, 95 % confidence interval (CI) 0.63-0.96, p = 0.02), whereas bleeding was higher (OR 1.55, 1.29-1.85, p < 0.01) compared with continued clopidogrel. Conversely, MACE was similar with switching to a novel agent and upfront novel therapy initiation (OR 1.01, 95 % CI 0.8-1.29, p = 0.90), but bleeding was higher in the switching group (OR 1.24, 95 % CI 1.03-1.48, p = 0.02). CONCLUSIONS: The current study suggests that switching to a novel P2Y12 agent in patients with ACS and/or patients undergoing coronary stenting is more efficacious than continuing clopidogrel. In this cohort, switching to a novel agent did not result in worse ischemic outcomes than upfront initiation of novel therapies. However, switching was associated with greater bleeding compared with both continued clopidogrel as well as upfront use of novel P2Y12 agents.

Impact of cardiac resynchronization therapy on hospitalizations in the Resynchronization-Defibrillation for Ambulatory Heart Failure trial.

BACKGROUND: This study reports the impact of cardiac resynchronization therapy (CRT) on hospitalizations in patients randomized to implantable cardioverter-defibrillator (ICD) or ICD-CRT in the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT). METHODS AND RESULTS: Hospitalization rates and lengths of hospital stay were compared between the 2 groups. At the 18-month follow-up, the numbers of patients hospitalized for any cause were similar in the ICD (n=351, 38.8%) and ICD-CRT (n=331, 30.0%) groups. The number of patients hospitalized for heart failure was significantly lower in the ICD-CRT (n=101, 11.3%) compared with the ICD (n=141, 15.6%; P=0.003) group. The number of patients hospitalized for a device-related indication was similar in the ICD-CRT group (n=147, 16.4%) and ICD group (n=126, 13.9%; P=0.148). The total number of hospitalizations for any cause (n=1448 versus n=1553; P=0.042), any cardiovascular cause (n=667 versus n=790; P=0.017), and any heart failure cause (n=385 versus n=505; P<0.0001) was significantly lower in ICD-CRT group compared with the ICD group, whereas the number of hospitalizations for device-related causes was significantly higher in the ICD-CRT group compared with the ICD group (246 versus 159; P<0.001). Although the reduction in hospitalizations for heart failure in the CRT-ICD group was offset by an increased number of hospitalizations for device-related indications, the length of hospital stay for any cause was significantly shorter in the ICD-CRT group (8.83±13.30 days) compared with the ICD group (9.59±14.40 days; P=0.005). CONCLUSION: ICD-CRT therapy significantly reduces hospitalizations and total days in hospital in patients with New York Heart Association class II/III heart failure compared with ICD therapy despite increased admissions for device-related indications. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251251.

Does stent strut design impact clinical outcomes: comparative safety and efficacy of Endeavor Resolute versus Resolute Integrity zotarolimus-eluting stents.

UNLABELLED: Percutaneous coronary intervention is the most commonly performed method of revascularizing obstructive coronary artery disease. The impact of stent strut design on clinical outcomes remains unclear. The Endeavour Resolute (ER-ZES) and the Resolute Integrity (RI-ZES) zotarolimus-eluting stents utilize identical polymers and anti-proliferative agents, differing only in their respective strut design. This study assessed the comparative safety and efficacy of these two stents in unrestricted contemporary real-world practice. METHODS: A total of 542 patients were identified, corresponding to 340 ER-ZES and 480 RI-ZES. The primary endpoint was major adverse cardiac events (MACE) defined by a composite of death, nonfatal myocardial infarction and stroke. Secondary endpoints included post-procedural length of stay, in-stent restenosis, target lesion revascularization, target vessel revascularization, coronary artery bypass grafting and stent thrombosis. RESULTS: MACE occurred in 3.2% of the ER-ZES cohort and 5.0% of the RI-ZES cohort (p= 0.43). Adjusted analysis utilizing propensity score-adjusted odds ratio for MACE, was 1.37 (95% CI 0.46-4.07, p=0.57). The mortality rate (0.9% ER-ZES vs. 1.9% RI-ZES, p=0.59), non-fatal MI (2.3% ER-ZES vs. 3.1% RI-ZES, p=0.75) and stroke (0.0% ER-ZES vs. 0.3% RI-ZES, p=0.85) were not different. Additionally, there was no difference in any of secondary outcomes. CONCLUSIONS: The clinical performance and safety of both ER-ZES and RI-ZES were not statistically different, despite differences in stent strut design.

Catheter-based renal sympathetic denervation: limitations to and gaps in the evidence.

PURPOSE OF REVIEW: Renal sympathetic nerves play a significant role in the development and maintenance of hypertension. Percutaneous catheter-based radioablation of the sympathetic nerves around the renal arteries is a true innovation in follow up to prior animal studies. In this opinion article, we will review the role of the renal sympathetic network in hypertension, and the evidence (or the lack of it) for renal sympathetic denervation as a treatment modality for human hypertension. RECENT FINDINGS: Over the last 5 years, path-breaking research has raised the promise of a dramatically effective therapy for treatment of resistant hypertension in the form of renal sympathetic denervation. Unfortunately, on the basis of limited proof-of-concept and prospective observational studies, this method was widely perceived as a proven therapy for resistant hypertension. As we have learnt from history, only properly designed prospective randomized controlled trials can tell whether that is indeed the truth. SUMMARY: Catheter-based renal sympathetic denervation, despite the recent setbacks, remains a novel and innovative therapeutic intervention, which may still have a role to play in the treatment of carefully selected patients with truly resistant hypertension. Mechanistic studies designed to address the cause of the blood pressure response (or lack thereof) to renal denervation are the next logical step. However, the long-term implications of renal denervation, especially safety issues with respect to the lack of renal sympathetic response in times of physiological need, are not well understood.

Granulocyte colony-stimulating factor therapy for stem cell mobilization following anterior wall myocardial infarction: the CAPITAL STEM MI randomized trial.

BACKGROUND: Small studies have yielded divergent results for administration of granulocyte colony-stimulating factor (G-CSF) after acute myocardial infarction. Adequately powered studies involving patients with at least moderate left ventricular dysfunction are lacking. METHODS: Patients with left ventricular ejection fraction less than 45% after anterior-wall myocardial infarction were treated with G-CSF (10 µg/kg daily for 4 days) or placebo. After initial randomization of 86 patients, 41 in the placebo group and 39 in the G-CSF group completed 6-month follow-up and underwent measurement of left ventricular ejection fraction by radionuclide angiography. RESULTS: Baseline and 6-week mean ejection fraction was similar for the G-CSF and placebo groups: 34.8% (95% confidence interval [CI] 32.6%-37.0%) v. 36.4% (95% CI 33.5%-39.2%) at baseline and 39.8% (95% CI 36.2%-43.4%) v. 43.1% (95% CI 39.2%-47.0%) at 6 weeks. However, G-CSF therapy was associated with a lower ejection fraction at 6 months relative to placebo (40.8% [95% CI 37.4%-44.2%] v. 46.0% [95% CI 42.7%-44.3%]). Both groups had improved left ventricular function, but change in left ventricular ejection fraction was lower in patients treated with G-CSF than in those who received placebo (5.7 [95% CI 3.4-8.1] percentage points v. 9.2 [95% CI 6.3-12.1] percentage points). One or more of a composite of several major adverse cardiac events occurred in 8 patients (19%) within each group, with similar rates of target-vessel revascularization. INTERPRETATION: In patients with moderate left ventricular dysfunction following anterior-wall infarction, G-CSF therapy was associated with a lower 6-month left ventricular ejection fraction but no increased risk of major adverse cardiac events. Future studies of G-CSF in patients with left ventricular dysfunction should be monitored closely for safety. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT00394498.

Challenges in the evaluation of aortic stenosis: A guide to multimodal imaging.

Severe Aortic stenosis (AS) is characterised by a late peaking crescendo-decrescendo systolic murmur and a diminished/absent second heart sound. Echocardiographic assessment of AS severity, based on transvalvular velocities / pressure gradients and calculated aortic valve area (AVA), confirms the diagnosis and allows timely intervention. Nevertheless, diagnostic uncertainty exists in cases of discordant measurements, confounders, and symptoms-measurement discrepancies. This guide outlines an approach to the use of multimodal imaging in the diagnosis and staging of AS.

Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial.

BACKGROUND: Prospective assessment of pharmacogenetic strategies has been limited by an inability to undertake bedside genetic testing. The CYP2C19*2 allele is a common genetic variant associated with increased rates of major adverse events in individuals given clopidogrel after percutaneous coronary intervention (PCI). We used a novel point-of-care genetic test to identify carriers of the CYP2C19*2 allele and aimed to assess a pharmacogenetic approach to dual antiplatelet treatment after PCI. METHODS: Between Aug 26, 2010, and July 7, 2011, 200 patients were enrolled into our prospective, randomised, proof-of-concept study. Patients undergoing PCI for acute coronary syndrome or stable angina were randomly assigned to rapid point-of-care genotyping or to standard treatment. Individuals in the rapid genotyping group were screened for the CYP2C19*2 allele. Carriers were given 10 mg prasugrel daily, and non-carriers and patients in the standard treatment group were given 75 mg clopidogrel daily. The primary endpoint was the proportion of CYP2C19*2 carriers with high on-treatment platelet reactivity (P2Y12 reactivity unit [PRU] value of more than 234) after 1 week of dual antiplatelet treatment, which is a marker associated with increased adverse cardiovascular events. Interventional cardiologists and data analysts were masked to genetic status and treatment. Patients were not masked to treatment allocation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, NCT01184300. FINDINGS: After randomisation, 187 patients completed follow-up (91 rapid genotyping group, 96 standard treatment). 23 individuals in each group carried at least one CYP2C19*2 allele. None of the 23 carriers in the rapid genotyping group had a PRU value of more than 234 at day 7, compared with seven (30%) given standard treatment (p=0·0092). The point-of-care genetic test had a sensitivity of 100% (95% CI 92·3-100) and a specificity of 99·3% (96·3-100). INTERPRETATION: Point-of-care genetic testing after PCI can be done effectively at the bedside and treatment of identified CYP2C19*2 carriers with prasugrel can reduce high on-treatment platelet reactivity. FUNDING: Spartan Biosciences.

Dipyridamole and vascular healing following stent implantation.

Introduction: Patients undergoing coronary stent implantation incur a 2% annual rate of adverse events, largely driven by in-stent restenosis (ISR) due to neointimal (NI) tissue proliferation, a process in which smooth muscle cell (SMC) biology may play a central role. Dipyridamole (DP) is an approved therapeutic agent with data supporting improved vascular patency rates. Pre-clinical data supports that DP may enact its vasculoprotective effects via adenosine receptor-A2B (ADOR-A2B). We sought to evaluate the efficacy of DP to mitigate ISR in a pre-clinical rabbit stent model. Methods & Results: 24 New Zealand White Rabbits were divided into two cohorts-non-atherosclerosis and atherosclerosis (n = 12/cohort, 6 male and 6 female). Following stent implantation, rabbits were randomized 1:1 to control or oral dipyridamole therapy for 6 weeks followed by optical coherence tomography (OCT) and histology assessment of NI burden and stent strut healing. Compared to control, DP demonstrated a 16.6% relative reduction in NI volume (14.7 ± 0.8% vs. 12.5 ± 0.4%, p = 0.03) and a 36.2% relative increase in optimally healed stent struts (37.8 ± 2.8% vs. 54.6 ± 2.5%, p < 0.0001). Atherosclerosis demonstrated attenuated effect with no difference in NI burden (15.2 ± 1.0% vs. 16.9 ± 0.8%, p = 0.22) and only a 14.2% relative increase in strut healing (68.3 ± 4.1% vs. 78.7 ± 2.5%, p = 0.02). DP treated rabbits had a 44.6% (p = 0.045) relative reduction in NI SMC content. In vitro assessment of DP and coronary artery SMCs yielded dose-dependent reduction in SMC migration and proliferation. Selective small molecule antagonism of ADOR-A2B abrogated the effects of DP on SMC proliferation. DP modulated SMC phenotypic switching with ADOR-A2B siRNA knockdown supporting its role in the observed effects. Conclusion: Dipyridamole reduces NI proliferation and improves stent healing in a preclinical model of stent implantation with conventional antiplatelets. Atherosclerosis attenuates the observed effect. Clinical trials of DP as an adjunctive agent may be warranted to evaluate for clinical efficacy in stent outcomes.

Off-Hours Presentation, Door-to-Balloon Time, and Clinical Outcomes in Patients Referred for Primary Percutaneous Coronary Intervention.

OBJECTIVES: Presentation with ST-segment-elevation myocardial infarction (STEMI) during off-hours may impact timely reperfusion and clinical outcomes. We investigated the association between off-hours presentation, door-to-balloon time, and in-hospital mortality in patients with STEMI referred for primary percutaneous coronary intervention (PCI). METHODS: We included consecutive patients referred for primary PCI at the University of Ottawa Heart Institute between July 2004 and December 2017. The off-hours group included patients presenting on weekends, statutory holidays, or between 18:00 to 07:59 hours on weekdays. The on-hours group included patients presenting between 08:00 and 17:59 hours on weekdays. The primary clinical outcome was the adjusted in-hospital mortality. The primary quality-of-care indicator was door-to-balloon time. RESULTS: A total of 5132 patients were included, with 3152 (61.4%) in the off-hours group and 1980 (38.6%) in the on-hours group. The median door-to-balloon time was longer in the off-hours group compared with the on-hours group (102 minutes vs 77 minutes; P<.001), while the median onset-to-door time was similar (P=.40). There was no difference in the rates of in-hospital mortality (3.5% vs 3.0%; P=.32) or in the adjusted mortality (odds ratio, 1.2; 95% confidence interval, 0.8-1.8; P=.44) between off-hours and on-hours groups. However, door-to-balloon time was an independent predictor of in-hospital mortality (P<.01) and off-hours presentation was an independent predictor of longer door-to-balloon time (P<.001), with an excess of 22.1 minutes. CONCLUSION: Patients treated with primary PCI during off-hours had longer door-to-balloon times. Treatment during off-hours was an independent predictor of longer door-to-balloon time and longer door-to-balloon times were associated with higher mortality.

Evaluation of a Rabbit Model of Vascular Stent Healing: Application of Optical Coherence Tomography.

Percutaneous coronary intervention (PCI) is a management strategy for symptomatic obstructive coronary artery disease (CAD). Despite advancements, in-stent restenosis (ISR) still imparts a 1-2% annual rate of repeat revascularization-a focus of ongoing translational research. Optical coherence tomography (OCT) provides high resolution virtual histology of stents. Our study evaluates the use of OCT for virtual histological assessment of stent healing in a rabbit aorta model, enabling complete assessment of intraluminal healing throughout the stent. ISR varies based on intra-stent location, stent length, and stent type in a rabbit model-important considerations for translational experimental design. Atherosclerosis leads to more prominent ISR proliferation independent of stent-related factors. The rabbit stent model mirrors clinical observations, while OCT-based virtual histology demonstrates utility for pre-clinical stent assessment. Pre-clinical models should incorporate clinical and stent factors as feasible to maximize translation to clinical practice.

Rationale and Design of the Rivaroxaban Post-Transradial Access for the Prevention of Radial Artery Occlusion Trial (CAPITAL-RAPTOR).

INTRODUCTION: Transradial access (TRA) has rapidly emerged as the preferred vascular access site for coronary angiography and percutaneous coronary intervention. Radial artery occlusion (RAO) remains as an important complication of TRA as it precludes future ipsilateral transradial procedures. While intraprocedural anticoagulation has been studied extensively, the definitive role of postprocedural anticoagulation has not yet been established. METHODS AND ANALYSIS: The Rivaroxaban Post-Transradial Access for the Prevention of Radial Artery Occlusion trial is a multicentre, prospective, randomised, open-label, blinded-endpoint design study investigating the efficacy and safety of rivaroxaban to reduce the incidence of RAO. Eligible patients will undergo randomisation to receive either rivaroxaban 15 mg once daily for 7 days or to no additional postprocedural anticoagulation. Doppler ultrasound to assess radial artery patency will be performed at 30 days. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ottawa Health Science Network Research Ethics Board (approval number 20180319-01H). The study results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03630055.

Association Between the Access Site for Coronary Angiography and Catheter-induced Coronary Artery Dissection.

Background: Catheter-induced coronary artery dissection (CICAD) is a rare complication of coronary angiography. The association between access site and CICAD remains unclear; however, transradial access (TRA) may be associated with a higher incidence of CICAD due to access vessel tortuosity and the mechanical disadvantage of catheters designed for the transfemoral access (TFA) approach. Methods: In this retrospective study, the reports of consecutive left heart catheterizations between April 2007, and December 2021 were reviewed for CICAD. Patients were excluded if the procedural report did not report an arterial access site. Identified CICAD cases were reviewed in detail. Results: There were 142/89,876 (0.16%) identified cases of CICAD. The access site was not associated with an increased risk of CICAD (0.18% with TRA vs 0.15% with TFA; relative risk [RR], 1.18; 95% CI, 0.84-1.65; P = .34) over the entire study period. With respect to TRA-related CICAD, male sex was associated with a decreased risk of dissection (RR, 0.64; 95% CI, 0.41-0.99; P = .04), but ST-elevation myocardial infarction at presentation was associated with an increased risk (RR, 3.01; 95% CI, 1.86-4.85; P < .01). In the TFA-predominant era, TRA was associated with an increased risk of CICAD (0.48% TRA vs 0.11% TFA; RR, 3.42; 95% CI, 2.05-5.69; P < .01)-an association that was not present in the TRA-predominant era. In-hospital mortality in patients with CICAD was 8.5%. Conclusions: CICAD is a rare complication of coronary angiography. Over a 15-year period, we did not demonstrate an association between access site and an increased risk of CICAD. There is substantial mortality associated with CICAD.