Resource Utilization and Costs Associated With Cardiogenic Shock Complicating Myocardial Infarction: A Population-Based Cohort Study.

Background: Cardiogenic shock due to acute myocardial infarction (AMI-CS) is associated with significant short- and long-term morbidity and mortality. Despite this, little is known about associated cost. Objectives: The purpose of this study was to evaluate the health care costs and resource use associated with AMI-CS using administrative data from the province of Ontario, Canada. Methods: This was a retrospective cohort study of adult patients with AMI-CS from April 2009 to March 2019. One-year costs following index admission were reported at an individual level. We used generalized linear models to identify factors associated with increased cost. We stratified patients by revascularization strategy to compare cost in each group and examined total cost at a patient level per individual fiscal year. Results: We included 9,789 consecutive patients with AMI-CS across 135 centers in Ontario (mean age 70.5 years; 67.7% male). Mortality in-hospital was 30.2%, and mortality at 2 years was 45.9%. The median inpatient cost per patient was $23,912 (IQR: $12,234-$41,833) with a median total 1-year cost of $37,913 (IQR: $20,113-$66,582). The median 1-year cost was $17,730 (IQR: $9,323-$38,379) for those who died in hospital, and $45,713 (IQR: $29,688-$77,683) for those surviving to discharge, with $12,719 (IQR: $4,262-$35,275) occurring after discharge. Patients who received coronary artery bypass grafting incurred the highest cost among revascularization groups. No significant differences were observed in cost per fiscal year from 2009 to 2019. Conclusions: AMI-CS is associated with significant health care costs, both during the index hospitalization and following discharge. To optimize cost-effectiveness, future therapies should aim to reduce disability in addition to improving mortality.

Persistent and Recurrent Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes.

BACKGROUND: Scarce data exist on the evolution of device-related thrombus (DRT) after left atrial appendage closure (LAAC). OBJECTIVES: This study sought to assess the incidence, predictors, and clinical impact of persistent and recurrent DRT in LAAC recipients. METHODS: Data were obtained from an international multicenter registry including 237 patients diagnosed with DRT after LAAC. Of these, 214 patients with a subsequent imaging examination after the initial diagnosis of DRT were included. Unfavorable evolution of DRT was defined as either persisting or recurrent DRT. RESULTS: DRT resolved in 153 (71.5%) cases and persisted in 61 (28.5%) cases. Larger DRT size (OR per 1-mm increase: 1.08; 95% CI: 1.02-1.15; P = 0.009) and female (OR: 2.44; 95% CI: 1.12-5.26; P = 0.02) were independently associated with persistent DRT. After DRT resolution, 82 (53.6%) of 153 patients had repeated device imaging, with 14 (17.1%) cases diagnosed with recurrent DRT. Overall, 75 (35.0%) patients had unfavorable evolution of DRT, and the sole predictor was average thrombus size at initial diagnosis (OR per 1-mm increase: 1.09; 95% CI: 1.03-1.16; P = 0.003), with an optimal cutoff size of 7 mm (OR: 2.51; 95% CI: 1.39-4.52; P = 0.002). Unfavorable evolution of DRT was associated with a higher rate of thromboembolic events compared with resolved DRT (26.7% vs 15.1%; HR: 2.13; 95% CI: 1.15-3.94; P = 0.02). CONCLUSIONS: About one-third of DRT events had an unfavorable evolution (either persisting or recurring), with a larger initial thrombus size (particularly >7 mm) portending an increased risk. Unfavorable evolution of DRT was associated with a 2-fold higher risk of thromboembolic events compared with resolved DRT.

Diagnostic accuracy of point-of-care ultrasound with artificial intelligence-assisted assessment of left ventricular ejection fraction.

Focused cardiac ultrasound (FoCUS) is becoming standard practice in a wide spectrum of clinical settings. There is limited data evaluating the real-world use of FoCUS with artificial intelligence (AI). Our objective was to determine the accuracy of FoCUS AI-assisted left ventricular ejection fraction (LVEF) assessment and compare its accuracy between novice and experienced users. In this prospective, multicentre study, participants requiring a transthoracic echocardiogram (TTE) were recruited to have a FoCUS done by a novice or experienced user. The AI-assisted device calculated LVEF at the bedside, which was subsequently compared to TTE. 449 participants were enrolled with 424 studies included in the final analysis. The overall intraclass coefficient was 0.904, and 0.921 in the novice (n = 208) and 0.845 in the experienced (n = 216) cohorts. There was a significant bias of 0.73% towards TTE (p = 0.005) with a level of agreement of 11.2%. Categorical grading of LVEF severity had excellent agreement to TTE (weighted kappa = 0.83). The area under the curve (AUC) was 0.98 for identifying an abnormal LVEF (<50%) with a sensitivity of 92.8%, specificity of 92.3%, negative predictive value (NPV) of 0.97 and a positive predictive value (PPV) of 0.83. In identifying severe dysfunction (<30%) the AUC was 0.99 with a sensitivity of 78.1%, specificity of 98.0%, NPV of 0.98 and PPV of 0.76. Here we report that FoCUS AI-assisted LVEF assessments provide highly reproducible LVEF estimations in comparison to formal TTE. This finding was consistent among senior and novice echocardiographers suggesting applicability in a variety of clinical settings.

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.

Long-Term Outcomes of Cardiogenic Shock Complicating Myocardial Infarction.

BACKGROUND: Cardiogenic shock secondary to acute myocardial infarction (AMI-CS) is associated with substantial short-term mortality; however, there are limited data on long-term outcomes and trends. OBJECTIVES: This study sought to examine long-term outcomes of AMI-CS patients. METHODS: This was a population-based, retrospective cohort study in Ontario, Canada of critically ill adult patients with AMI-CS who were admitted to hospitals between April 1, 2009 and March 31, 2019. Outcome data were captured using linked health administrative databases. RESULTS: A total of 9,789 consecutive patients with AMI-CS from 135 centers were included. The mean age was 70.5 ± 12.3 years, and 67.7% were male. The incidence of AMI-CS was 8.2 per 100,000 person-years, and it increased over the study period. Critical care interventions were common, with 5,422 (55.4%) undergoing invasive mechanical ventilation, 1,425 (14.6%) undergoing renal replacement therapy, and 1,484 (15.2%) receiving mechanical circulatory support. A total of 2,961 patients (30.2%) died in the hospital, and 4,004 (40.9%) died by 1 year. Mortality at 5 years was 58.9%. Small improvements in short- and long-term mortality were seen over the study period. Among survivors to discharge, 2,870 (42.0%) required increased support in care from their preadmission baseline, 3,244 (47.5%) were readmitted to the hospital within 1 year, and 1,047 (15.3%) died within 1 year. The mean number of days at home in the year following discharge was 307.9 ± 109.6. CONCLUSIONS: Short- and long-term mortality among patients with AMI-CS is high, with minimal improvement over time. AMI-CS survivors experience significant morbidity, with high risks of readmission and death. Future studies should evaluate interventions to minimize postdischarge morbidity and mortality among AMI-CS survivors.

Efficacy of Milrinone and Dobutamine in Cardiogenic Shock: An Updated Systematic Review and Meta-Analysis.

OBJECTIVES: Inotropic support is commonly used in patients with cardiogenic shock (CS). High-quality data guiding the use of dobutamine or milrinone among this patient population is limited. We compared the efficacy and safety of these two inotropes among patients with low cardiac output states (LCOS) or CS. DATA SOURCES: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched up to February 1, 2023, using key terms and index headings related to LCOS or CS and inotropes. DATA EXTRACTION: Two independent reviewers included studies that compared dobutamine to milrinone on all-cause in-hospital mortality, length of ICU stay, length of hospital stay, and significant arrhythmias in hospitalized patients. DATA SYNTHESIS: A total of eleven studies with 21,084 patients were included in the meta-analysis. Only two randomized controlled trials were identified. The primary outcome, all-cause mortality, favored milrinone in observational studies only (odds ratio [OR] 1.19 (95% CI, 1.02-1.39; p = 0.02). In-hospital length of stay (LOS) was reduced with dobutamine in observational studies only (mean difference -1.85 d; 95% CI -3.62 to -0.09; p = 0.04). There was no difference in the prevalence of significant arrhythmias or in ICU LOS. CONCLUSIONS: Only limited data exists supporting the use of one inotropic agent over another exists. Dobutamine may be associated with a shorter hospital LOS; however, there is also a potential for increased all-cause mortality. Larger randomized studies sufficiently powered to detect a difference in these outcomes are required to confirm these findings.

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.

Inotrope versus placebo therapy in cardiogenic shock: Rationale and study design of the CAPITAL DOREMI2 trial.

BACKGROUND: Cardiogenic shock (CS) is a state of end-organ hypoperfusion related to cardiac dysfunction. Current guidelines recommend consideration of inotrope therapy in patients with CS, however no robust data support their use. The purpose of the CAPITAL DOREMI2 trial is to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of patients with CS. METHODS AND DESIGN: This is a multi-center, double-blind, randomized, placebo-controlled trial comparing single-agent inotrope therapy to placebo in patients with CS. A total of 346 participants with Society for Cardiovascular Angiography and Interventions class C or D CS will be randomized in a 1:1 fashion to inotrope or placebo therapy, which will be administered over a 12-hour period. After this period, participants will continue open-label therapies at the discretion of the treating team. The primary outcome is a composite of all-cause in-hospital death, and, as measured during the 12-hour intervention period, any of: sustained hypotension or high dose vasopressor requirements, lactate greater than 3.5 mmol/L at 6 hours or thereafter, need for mechanical circulatory support, arrhythmia leading to emergent electrical cardioversion, and resuscitated cardiac arrest. All participants will be followed for the duration of their hospitalization, and secondary outcomes will be assessed at the time of discharge. IMPLICATION: This trial will be the first to establish the safety and efficacy of inotrope therapy against placebo in a population of patients with CS and has the potential to alter the standard care provided to this group of patients.

Arrhythmic Events and Mortality in Patients With Cardiogenic Shock on Inotropic Support: Results of the DOREMI Randomized Trial.

BACKGROUND: Inotropic support is widely used in the management of cardiogenic shock (CS). Existing data on the incidence and significance of arrhythmic events in patients with CS on inotropic support is at high risk of bias. METHODS: The Dobutamine Compared to Milrinone (DOREMI) trial randomized patients to receive dobutamine or milrinone in a double-blind fashion. Patients with and without arrhythmic events (defined as arrhythmias requiring intervention or sustained ventricular arrhythmias) were compared to identify factors associated with their occurrence, and to examine their association with in-hospital mortality and secondary outcomes. RESULTS: Ninety-two patients (47.9%) had arrhythmic events, occurring equally with dobutamine and milrinone (P = 0.563). The need for vasopressor support at initiation of the inotrope and a history of atrial fibrillation were positively associated with arrhythmic events, whereas predominant right ventricular dysfunction, previous myocardial infarction, and increasing left ventricular ejection fraction were negatively associated with them. Supraventricular arrhythmic events were not associated with mortality (relative risk [RR], 0.97; 95% confidence interval [CI], 0.68-1.40; P = 0.879) but were positively associated with resuscitated cardiac arrests and hospital length of stay. Ventricular arrhythmic events were positively associated with mortality (RR, 1.66; 95% CI, 1.13-2.43; P = 0.026) and resuscitated cardiac arrests. Arrhythmic events were most often treated with amiodarone (97%) and electrical cardioversion (27%), which were not associated with mortality. CONCLUSIONS: Clinically relevant arrhythmic events occur in approximately one-half of patients with CS treated with dobutamine or milrinone and are associated with adverse clinical outcomes. Five factors may help to identify patients most at risk of arrhythmic events.

Milrinone vs Dobutamine for the Management of Cardiogenic Shock: Implications of Renal Function and Injury.

Background: Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction. Objectives: This study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function. Methods: In this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m2 and acute kidney injury (AKI). The primary outcome was the 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, or initiation of renal replacement therapy. Results: Baseline eGFR <60 ml/min/1.73 m2 and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m2 did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome (P interaction = 0.02) and death (P interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI. Conclusions: In patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI.

Plasminogen Activator Inhibitor-1-Positive Platelet-Derived Extracellular Vesicles Predicts MACE and the Proinflammatory SMC Phenotype.

Patients with established coronary artery disease remain at elevated risk of major adverse cardiac events. The goal of this study was to evaluate the utility of plasminogen activator inhibitor-1-positive platelet-derived extracellular vesicles as a biomarker for major adverse cardiac events and to explore potential underlying mechanisms. Our study suggests these extracellular vesicles as a potential biomarker to identify and a therapeutic target to ameliorate neointimal formation of high-risk patients.

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.

Impact of atrial fibrillation on the risk of major adverse cardiac events following coronary revascularisation.

OBJECTIVE: Atrial fibrillation (AF) remains a highly prevalent arrhythmia with significant burden on morbidity and mortality. The impact of AF in the revascularised population remains incompletely described. Given the high prevalence of AF in the revascularised population, we sought to evaluate the incidence and prognosis in patients with pre-existing and new-onset AF following revascularisation. METHODS: We used the University of Ottawa Heart Institute Revascularisation Registry to identify patients who underwent revascularisation between August 2015 and March 2020, who were prospectively followed for an average of one year. We conducted a retrospective cohort study analysing the association between AF and clinical outcomes. The primary outcome of interest was 1-year major adverse cardiac events (MACE) defined as a composite of death, myocardial infarction, unplanned revascularisation and cerebrovascular accidents. Moreover, secondary outcomes include the individual components of MACE and bleeding. RESULTS: A total of 6704 patients underwent revascularisation and completed 1-year clinical follow-up. Median time to follow-up was 12.8 (IQR 11.2-15.9) months. One-year MACE occurred in 166 (21.8%) and 683 (11.5%) patients in AF and non-AF groups, respectively (adjusted HR, 1.61; 95% CI 1.29 to 2.01; p<0.0001). AF was independently predictive of 1-year mortality, myocardial infarction, unplanned revascularisation, cerebrovascular accident and bleeding. Within 1 year, 299 (4.5%) episodes of new-onset AF was observed. New-onset AF following revascularisation was also associated with 1-year MACE, mortality, myocardial infarction, cerebrovascular accident and unplanned revascularisation. CONCLUSIONS: Preprocedural and new-onset AF following revascularisation remains highly predictive 1-year MACE. AF should be considered in addition to traditional risk factors for adverse outcomes following revascularisation.

Transcatheter Edge-to-Edge Mitral Valve Repair in Patients With Severe Mitral Regurgitation and Cardiogenic Shock.

BACKGROUND: Data on the efficacy of transcatheter edge-to-edge repair (TEER) in patients with cardiogenic shock (CS) are limited. OBJECTIVES: This study investigated the characteristics and outcomes of consecutive patients with significant mitral regurgitation (MR) and CS who underwent TEER. METHODS: The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry was assessed from November 22, 2013, to December 31, 2021. CS was defined as the coding of: 1) CS; 2) inotrope use; or 3) mechanical circulatory support before TEER. Device success was defined as MR reduction of ≥1 grade and a final MR grade ≤2+. The primary outcome was the impact of device success on 1-year mortality or heart failure (HF) readmissions. Cox proportional hazards models were used to report the risk-adjusted association between device success and 1-year outcomes. RESULTS: A total of 3,797 patients met the inclusion criteria. Mean age was 73.0 ± 11.9 years, and 59.5% were male. Mean Society of Thoracic Surgery score (MV repair) was 14.9% ± 15.3%. MR etiology was degenerative (53.4%) and functional (27.5%). Device success was achieved in 3,249 (85.6%) patients given successful achievement of final MR grade ≤2+ (88.2%) and MR reduction ≥1 absolute grade (91.4%). At 1 year after TEER, device success was associated with significantly lower all-cause mortality (34.6% vs 55.5%; adjusted HR: 0.49; 95% CI: 0.41-0.59; P < 0.001) and a composite of mortality or HF admissions (29.6% vs 45.2%; adjusted HR: 0.51; 95% CI: 0.42-0.62; P < 0.001). CONCLUSIONS: Successful MR reduction is achievable in most patients with CS and is associated with significantly lower mortality and HF hospitalization at 1 year. Randomized trials assessing TEER in CS are needed to establish this potential therapeutic approach.