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.

Previous reports on the impact of preexisting atrial fibrillation (AF) on clinical outcomes after transcatheter aortic valve implantation (TAVI) have presented limited data on the relative impact of paroxysmal versus persistent AF subtypes. We compared in-hospital, 1-year, and late clinical outcomes in 1,098 patients who underwent TAVI with preoperative AF (556 paroxysmal, 542 persistent) versus 1,787 patients without AF. The propensity-matched cohorts with AF (n = 643) and without AF (n = 686) did not differ with respect to baseline clinical characteristics, operative technique, or in-hospital TAVI complications. At 1-year, patients with AF 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 Kansas City cardiomyopathy questionnaire scores (77.8 ± 21.8 vs 84.3 ± 17.1, p <0.001). Echocardiographic follow-up (mean time 455 ± 285 days) demonstrated no significant intergroup differences in hemodynamic findings other than a progressive increase in left atrial volume index in patient subgroups (without 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 to 52.9] months), patients with persistent AF had worse all-cause mortality than patients without AF (hazard ratio 1.55, 95% confidence interval 1.17 to 2.06, p = 0.003), with no significant survival differences between the paroxysmal AF and without AF subgroups. In conclusion, patients with preexisting AF and patients without AF who underwent TAVI had similar in-hospital outcomes but worse 1-year mortality, hospital readmission, and quality of life outcomes. Compared with patients without AF, 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 left atrial volume index than patients with paroxysmal AF and patients without AF 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.

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.

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.