Hemiplegic migraine episode triggered by regadenoson.

SPECT and PET myocardial perfusion imaging (MPI) are widely used to evaluate patients for coronary artery disease. Regadenoson (a selective A2A adenosine receptor agonist) is a commonly used vasodilator agent for stress MPI because of its safety profile and ease of use. Common adverse reactions such as headache, shortness of breath, flushing, and chest and abdominal discomfort are typically mild and can be effectively reversed using methylxanthines such as aminophylline and caffeine. Neurological adverse reactions such as seizure and stroke have rarely been reported with the use of regadenoson. The hemodynamic changes associated with regadenoson administration, such as an exaggerated hypotensive or hypertensive response, may be the cause for the reported cerebrovascular accidents. Activation of central nervous system A2A adenosine receptors is thought to be responsible for seizure episodes in patients with or without known histories of seizure. A2A adenosine receptors activation is also believed to play a role in headaches and migraine. This patient reported who has a history of hemiplegic migraine developed left side weakness and headache following the administration of regadenoson during a PET MPI study. Imaging work-up to rule out cerebrovascular accident was normal. After 1 hour from the onset of his symptoms, his weakness and headache significantly improved with complete resolution within 24 hours. We concluded that regadenoson triggered a hemiplegic migraine episode in this patient, which has not been previously reported in the literature. It may be prudent to avoid regadenoson and adenosine use in patients with a history of hemiplegic migraine.

Entrepreneur fund-seeking: toward a theory of funding fit in the era of equity crowdfunding.

Why do entrepreneurs prefer to seek one equity form of funding over another? To address this question, we develop a contingency-based model of perceived funding fit that delineates several factors that influence strategic fund-seeking decisions by entrepreneurs. In prior research, entrepreneur fund-seeking has largely been explained using models that rely on rule-based approaches (e.g., the pecking order assumption) or value capture considerations. In contrast, we propose a dynamic contingency-based model that delineates several factors that influence entrepreneur perceptions of funding fit over and above transactional efficiency, including atypical value creation from the fundraising process itself and external stakeholder values. We inductively assess our model in the context of equity crowdfunding (ECF) and find that perceived funding fit can motivate some strategic fund-seekers to opt to pursue ECF, even when they have a reasonable opportunity to obtain other more established sources of funding such as angel or seed-stage venture capital. This indicates that ECF in several cases is not a funding mode of last resort as proposed in prior literature. Plain English Summary Raising capital is a complex and dynamic process. Strategic entrepreneurs seek "funding fit" for their particular ventures leading some to opt for less established forms of funding such as equity crowdfunding for a variety of reasons beyond efficiency. Prior venture funding research has largely taken the view of the investor, emphasizing what entrepreneurs must do to win the favor of angel investors and other seed funders, and deeming equity crowdfunding (ECF) a funding mode of last resort for discouraged entrepreneurs. Inductively analyzing hundreds of regulatory filings, entrepreneur interviews, public information, and media pieces about ECF-funded firms, we find evidence that in several cases, strategic entrepreneurs may prefer to opt for ECF if they perceive it to be a better fit due to novel forms of nonfinancial value. We explain our findings by proposing an emergent contingency-based model of "funding fit."

Variation in platelet expression of FcγRIIa after myocardial infarction.

FcγRIIa amplifies platelet activation and greater platelet expression of FcγRIIa identifies patients at greater risk of subsequent cardiovascular events. Thus, platelet expression of FcγRIIa may be useful to guide therapy. Because platelet function tests are impacted by preparative procedures and substantial intra-individual variability, we examined the impact of these factors on platelet expression of FcγRIIa in blood from healthy subjects and in patients after myocardial infarction (MI). Platelet expression of FcγRIIa was quantified with the use of flow cytometry. Blood was taken from healthy subjects and 114 patients after a MI in whom platelet expression of FcγRIIa was quantified before discharge and at 6 ± 1 months. Neither anticoagulants nor the antiplatelet agent cangrelor changed platelet expression of FcγRIIa. Intra-individual variation in platelet FcγRIIa expression was 8.5% ± 5% over the course of 1 month in healthy subjects. Platelet FcγRIIa expression was within 20% of the baseline value after 6 months in 71% of patients after MI. In summary, because FcγRIIa is a protein on the surface of platelets, assay conditions and antiplatelet agents do not change expression. Intra-individual variability in platelet expression of FcγRIIa is modest. Accordingly, platelet expression of FcγRIIa is a marker of increased platelet reactivity that can be reliably and repeatedly measured.Clinical Trial Registration: NCT02505217.

Impact of Persistent Versus Paroxysmal Preoperative Atrial Fibrillation on In-Hospital, One-Year and Late Clinical Outcomes Following Transcatheter Aortic Valve Implantation.

Prior reports on the impact of pre-existing atrial fibrillation (AF) on clinical outcomes following transcatheter aortic valve implantation (TAVI) have presented limited data on the relative impact of paroxysmal versus persistent AF sub-types. We compared in-hospital, 1-year and late clinical outcomes in 1,098 TAVI patients with preoperative AF (556 paroxysmal, 542 persistent) versus 1,787 No-AF patients. Propensity matched AF (n=643) and No-AF (n=686) cohorts did not differ with respect to baseline clinical characteristics, operative technique or in-hospital TAVI complications. At 1-year, AF patients had higher all-cause mortality (9.0 vs 6.1%, p=0.046) and readmission rates (13.1 vs 8.8%, p=0.014), with lower KCCQ12 scores (77.8±21.8 vs 84.3±17.1, p<0.001). Echocardiographic follow-up (mean time 455 ± 285 days) demonstrated no significant inter-group differences in hemodynamic findings other than a progressive increase in left atrial volume index (LAVI) in patient subgroups (No-AF:37.4±14.7 ml/m2 vs paroxysmal AF: 46.4±21.4 ml/m2 vs persistent AF: 60.5±26.3 ml/m2; p<0.001). On late follow-up (mean time 49.0 (45.1-52.9) months), patients with persistent AF had worse all-cause mortality compared to No-AF patients (HR: 1.55; 95% CI: 1.17-2.06, p=0.003), with no significant survival differences between the paroxysmal AF and No-AF subgroups. In conclusion, pre-existing AF compared to No-AF TAVI patients had similar in-hospital outcomes, but worse 1-year mortality, hospital readmission and quality of life outcomes. Compared to No-AF patients, patients with persistent, but not paroxysmal preexisting AF, have higher late all-cause mortality at a mean follow-up of 49 months. Patients with persistent AF have higher levels of LAVI compared to paroxysmal and No-AF patients on intermediate echocardiographic follow-up.

Feasibility of stress only rubidium-82 PET myocardial perfusion imaging.

BACKGROUND: Stress only SPECT myocardial perfusion imaging (MPI) is a validated strategy to streamline cardiac diagnostic imaging. The potential use of Rb82 PET stress only MPI has not been investigated. METHODS AND RESULTS: Stress images from 200 Rb82 PET-MPI were reviewed by two blinded readers and categorized as not requiring additional rest images (normal) or requiring additional images (abnormal or equivocal). No additional images were deemed necessary for 95 (48%) and 99 (50%) by the two blinded readers. The stress only interpretation was compared to the previous read of the complete rest-stress study. The rate of detecting a normal result with stress only reading was 76%-79% with a negative predictive value of 94%-95%. Clinical predictors of a normal stress only PET-MPI included lower age, the absence of CAD, and female gender, but not body mass index. Blinded reads of 50 additional consecutive PET-MPI from patients with selected clinical predictors (age <65 years, no known CAD) were then performed. Of these, 40 (80%) were normal by previous rest-stress reading, and 34 (68%) were categorized as not requiring additional images after stress only reading. PET stress only imaging would have resulted in a mean reduction of radiation exposure of 2.4 mSv per study according to a published radiation estimate. CONCLUSION: Stress only Rb82 PET-MPI is a feasible strategy to reduce resource utilization and radiation exposure associated with MPI. This strategy would be most applicable to patients with a lower pretest likelihood.

Stress-First Myocardial Perfusion Imaging.

Stress-first approaches to myocardial perfusion imaging provide diagnostically and prognostically accurate perfusion data equivalent to a full rest-stress study while saving time in the imaging laboratory and reducing the radiation exposure to patients and laboratory staff. Unfortunately, implementing a stress-first approach in a nuclear cardiology laboratory involves significant challenges such as the need for attenuation correction, triage of patients to an appropriate protocol, real-time review of stress images, and consideration of differential reimbursement. Despite it being best practice for both the patient and the laboratory, these impediments have kept the proportions of studies performed stress-first relatively unchanged in North America and world-wide in the last 10 years.

Intermediate Follow-Up of Balloon-Expandable Versus Self-Expanding Transcatheter Aortic Valve Implantation in Patients With Small Aortic Annuli.

The clinical impact of prosthesis-patient mismatch (PPM) in patients with small aortic annuli who underwent transcatheter aortic valve (AV) implantation with either balloon-expandable (BE) or self-expanding (SE) valves remains controversial. We assessed in-hospital and intermediate clinical outcomes in 573 patients with transfemoral transcatheter AV implantation with a small AV annulus, defined as an AV annulus area ≤430 mm2. A total of 337 patients treated with a 23-mm BE valve (SAPIEN 3, Ultra) were compared with 236 patients treated with a 26-mm SE valve (Evolut series). Valve-in-valve cases were excluded, and late echo follow-up (mean 674 ± 438 days) was assessed in a subset of 292 patients (51.0%). Well-matched BE and SE cohorts did not differ with respect to major in-hospital outcomes, other than a borderline increase in vascular complications and composite bleeding in patients with SE. Patients with BE had a higher incidence of severe PPM on discharge echocardiography (16.9% vs 6.8%, p <0.002). The mean AV gradient at 30 days was higher for patients with BE (12.2 ± 4.2 vs 6.2 ± 7.9 mm Hg, p <0.001) and at late follow-up (14.0 ± 8.2 vs 7.2 ± 3.5 mm Hg, p <0.001). The follow-up left ventricular ejection fraction and incidence of >mild aortic insufficiency were similar. All-cause mortality for the 2 cohorts was similar, with an overall mean (95% confidence interval) survival time of 61.2 months (57.8 to 64.5; p = 0.98). There were no significant survival differences between combined patients with BE and SE with no, moderate, or severe PPM, with an overall mean (95% confidence interval) survival time of 32.5 (30.5 to 34.5) months combining valve types (p = 0.23). In conclusion, despite an increased incidence of PPM with higher mean AV gradients that persist on late echocardiography in the BE cohort, patients with BE and SE with small aortic annuli have similar clinical outcomes at intermediate follow-up. Moderate and severe PPM had no impact on survival at a mean follow-up of 32.5 months.

Impact of Ticagrelor Versus Clopidogrel on Bleeding Outcomes of Isolated Coronary Artery Bypass Grafting.

BACKGROUND: Increased bleeding risks have been documented in patients exposed to P2Y12 inhibitors within 5 days of coronary artery bypass surgery (CABG). This study aimed to determine the relative CABG bleeding risks of clopidogrel versus ticagrelor exposure and the proper time course of ticagrelor discontinuation prior to surgery. METHODS: Clinical outcomes were assessed in 2075 isolated CABG patients, including 375 who had received P2Y12 inhibitors within 5 days of surgery (155 clopidogrel, 213 ticagrelor, 7 prasugrel). BARC-4 CABG bleeding complications and perioperative blood product usage were assessed in propensity-matched P2Y12-inhibited and non-P2Y12-inhibited cohorts. RESULTS: P2Y12-inhibited patients (n = 375) in comparison to matched non-P2Y12-inhibited patients (n = 1138) had higher rates of re-operation for bleeding (3.8 % vs 1.3 %, p = 0.003), postoperative red blood cell transfusion ≥5 units (5.7 % vs 2.7 %, p = 0.007), and intraoperative and postoperative blood product utilization (42.3 % vs 27.1 %, p < 0.001; 41.8 % vs 32.2 %, p < 0.001, respectively). Univariate predictors of BARC-4 bleeding included clopidogrel (OR: 2.145, 95 % CI: 1.131-4.067, p = 0.019) and ticagrelor discontinued within 3 days of surgery (OR: 2.153, 95 % CI: 1.003-4.169, p = 0.049). Multivariate logistic regression demonstrated that only clopidogrel exposure was an independent BARC-4 bleeding predictor (OR: 1.850, 95 % CI: 1.007-3.398, p = 0.048). Unadjusted ticagrelor patients with drug discontinuation 4-5 days prior to CABG only demonstrated higher rates of perioperative platelet transfusion, without additional signs of excessive bleeding. CONCLUSIONS: Clopidogrel exposure within 5 days of CABG is an independent predictor of BARC-4 bleeding, whereas major ticagrelor bleeding effects are confined to drug exposure within 3 days of surgery.

Propensity-matched comparison of right mini-thoracotomy versus median sternotomy for isolated mitral valve repair.

BACKGROUND: A right mini-thoracotomy (RT) versus median sternotomy (MS) approach for isolated mitral valve (MV) repair has been associated with less postoperative morbidity, shorter hospital stay, and faster functional recovery, but with consistently longer cross-clamp time and higher operative costs. METHODS: We assessed the impact of a modified operative technique on outcomes in 158 RT versus 129 MS patients treated with myxomatous MV repair from 2016 through 2021. Propensity matching based upon the Society of Thoracic Surgeons Risk Score was used to compare 108 patients in each cohort. RESULTS: Propensity-matched RT patients had reductions in total ventilation time (P=0.025), postoperative atrial fibrillation (P=0.019), and hospital length of stay (P<0.001). RT and MS patients had similar cross-clamp times (66.4±13.7 vs 64.8±16.0 minutes, P=0.414), with less overall leaflet resection (32.4% vs 57.4%, P<0.001) and fewer Gore-Tex NeoChords implanted per patient (1.7±0.7 vs 2.1±1.0, P=0.028) in the RT group. The two cohorts did not differ with respect to 30-day major surgical complications. No patient died and there was no difference between the two groups with respect to freedom from re-operation (98.2% vs 98.2%, P=0.800) at a mean follow-up of 21.4±18.5 months. Direct total hospital costs were lower for the RT group (P=0.018), with reductions in postoperative charges offsetting increased operating room costs. CONCLUSIONS: In this single-center study, the RT compared to the MS approach for myxomatous MV repair resulted in less postoperative morbidity and shorter hospital length of stay, with similar cross-clamp time, reduced total hospital costs, and comparable intermediate outcomes.

Tablet-Based Limited Echocardiography to Reduce Sonographer Scan and Decontamination Time during the COVID-19 Pandemic.

BACKGROUND: Limited assessments with handheld ultrasound have found meaningful clinical use in the care of acutely ill patients. However, there are limited data on incorporating handheld-based limited echocardiography into the echocardiography laboratory. The purpose of this study was to assess the efficacy of limited handheld tablet echocardiography as an alternative to traditional echocardiography during the coronavirus disease 2019 (COVID-19) pandemic as a means to limit exposure while providing essential clinical information. METHODS: Ninety consecutive inpatients with known or suspected COVID-19 were scanned according to laboratory COVID-19 guidelines using a limited 11- to 20-clip protocol on a tablet sonograph. The primary assessment was length of study time. Comparison data were drawn from comprehensive echocardiographic examinations ordered on intensive care patients not under COVID-19 precautions. RESULTS: Over a 36-day time period, a total of 91 requests were deemed to be appropriate for echocardiography on patients with suspected or confirmed COVID-19 (average age, 67 years; 64% men; mean body mass index, 32 kg/m2). Of these, 90 (99%) examinations were performed using a handheld device, and all were deemed diagnostic and provided sufficient information for the clinical care team. Sonographer scan time decreased from an average of 24 ± 6.8 min on a traditional platform to 5.4 ± 1.9 min on a tablet. CONCLUSIONS: Limited handheld echocardiography can be successfully implemented in the echocardiography laboratory for screening of COVID-19-related cardiac conditions. The protocol performed with handheld tablet ultrasound provides adequate diagnostic information of major cardiac complications of COVID-19 while decreasing sonographer contact and simplifying decontamination.

Assessment of Cardiovascular Risk by the Combination of Clinical Risk Scores Plus Platelet Expression of FcγRIIa.

Platelet expression of FcγRIIa was quantified after myocardial infarction (MI) and we found that patients with high platelet FcγRIIa expression (>11,000/platelet) had a fourfold greater risk of subsequent MI, stroke, and death. This analysis of the original cohort of 197 patients was designed to determine whether platelet expression of FcγRIIa could be used in combination with clinical risk scores (GRACE [Global Registry of Acute Coronary Events] and DAPT [Dual Antiplatelet Therapy]) to refine cardiovascular risk assessment. Platelet expression of FcγRIIa quantified with the use of flow cytometry was broadly distributed in patients stratified into high and low risk groups based on clinical risk scores. In patients identified as high risk by the GRACE score, 62% had high platelet FcγRIIa expression. Similarly, in patients identified as high risk by DAPT, 55% had high platelet FcγRIIa expression. High platelet FcγRIIa expression discriminated high and low risk cohorts in patients with high cardiovascular risk defined by either the GRACE score (high platelet FcγRIIa 18.9% vs low platelet FcγRIIa 0%; odds ratio = 15.7, p = 0.06) or the DAPT score (high platelet FcγRIIa 15.4% vs low platelet FcγRIIa 3.7%; odds ratio = 5.6, p = 0.03) assessment. Platelet expression of FcγRIIa merits additional study to determine whether low platelet FcγRIIa expression can be used to guide early transition to aspirin monotherapy and high platelet FcγRIIa expression can be used to guide continuation of DAPT.

The role of cardiac rehabilitation in patients with heart disease.

Cardiac rehabilitation is a valuable treatment for patients with a broad spectrum of cardiac disease. Current guidelines support its use in patients after acute coronary syndrome, coronary artery bypass grafting, coronary stent placement, valve surgery, and stable chronic systolic heart failure. Its use in these conditions is supported by a robust body of research demonstrating improved clinical outcomes. Despite this evidence, cardiac rehabilitation referral and attendance remains low and interventions to increase its use need to be developed.

Novel oral anticoagulants in the management of coronary artery disease.

Despite advances in interventional and pharmacologic therapy, survivors of myocardial infarction remain at an increased risk of subsequent cardiovascular events. Initial pharmacological management includes both platelet inhibition and parenteral anticoagulation, whereas long-term pharmacological therapy relies on antiplatelet therapy for prevention of thrombotic complications. Biomarkers showing ongoing thrombin generation after acute coronary syndromes suggest that anticoagulants may provide additional benefit in reducing cardiovascular events. We review the pharmacokinetics of novel anticoagulants, clinical trial results, the role of monitoring, and future directions for the use of novel oral anticoagulants in the treatment of coronary artery disease. Clinical trials have shown that long-term use of oral anticoagulants decreases the risk of cardiovascular events, but they do so at a cost of an increased risk of bleeding. Future studies will need to identify optimal treatment combinations for selected patients and conditions that address both the appropriate combination of therapy and the appropriate dosage of each agent when used in combination.