Mid America Heart Institute

BACKGROUND:The objective of this study is to describe the rationale and design of the multicenter phase 3 Research with EVuzamitide to Evaluate for cardiac AmyLoidosis (REVEAL) trial evaluating the diagnostic performance of 124I-evuzamitide positron emission tomography/computed tomography (PET/CT) for detection of cardiac amyloidosis (CA) in patients undergoing evaluation for suspected disease. 124I-evuzamitide is a novel fibril-targeting positron-emitting radiotracer that binds hypersulfated heparan sulfate glycans in amyloid fibrils across multiple amyloid subtypes. METHODS:This open-label, single-arm study, enrolled adults with suspected CA at 18 USA centers. Participants with previously diagnosed CA or systemic amyloidosis with known organ involvement, precursor protein targeted therapy use, estimated glomerular filtration rate less than 15 mL/min/1.73 m2, recent myocardial infarction, or recent heparin exposure were excluded. Cardiac and partial-body static PET/CT imaging was performed 4 ± 1 hour after intravenous administration of 124I-evuzamitide (1.0 ± 0.1 mCi). Potassium iodide was administered to reduce thyroid uptake of free radioiodine. Three blinded expert physicians independently assessed myocardial tracer uptake visually on PET/CT scans. Separately, three blinded amyloidosis experts adjudicated the presence or absence of CA using standard-of-care clinical, laboratory, biopsy, genetic, electrocardiographic, echocardiographic, cardiac magnetic resonance, and bone-avid tracer cardiac scintigraphy data. The primary endpoints were the sensitivity and specificity of visually interpreted 124I-evuzamitide PET/CT for the diagnosis of CA compared with the adjudicated standard-of-care diagnosis. CONCLUSIONS:REVEAL is the first multicenter phase 3 study evaluating a fibril-targeted PET radiotracer for the diagnosis of CA and may establish a noninvasive molecular imaging approach for detecting cardiac and systemic amyloid deposition across multiple amyloid subtypes.

BACKGROUND:A recent phase 3 study of the PET perfusion tracer F-18 flurpiridaz (flurpiridaz) met the primary efficacy endpoint for the detection of CAD, demonstrating statistically higher sensitivity, non-inferior specificity compared to Tc-99m-tetrofosmin/sestamibi SPECT (Tc99m-SPECT) in the general population. This study reports a pre-specified subgroup analysis examining the diagnostic accuracy of flurpiridaz in women. METHODS:Patients with suspected CAD underwent rest-stress flurpiridaz PET and Tc99m-SPECT before invasive coronary angiography in the US, Canada, and Europe. The primary endpoint was sensitivity and specificity by 2 expert readers (majority rule between 3 blinded readers) for the diagnosis of significant CAD defined as a stenosis ≥50%. Secondary endpoints included comparison of the diagnostic performance of flurpiridaz PET and Tc99m-SPECT. RESULTS:188 women were included in the subgroup analysis. Flurpiridaz met the pre-specified primary endpoint of sensitivity [82.9% (95% CI: 71.4, 94.4), P = 0.0014] and specificity [72.8% (95%CI: 65.6, 80),P = 0.0008]. Flurpiridaz sensitivity was significantly higher than Tc99m-SPECT [82.9% vs 65.9%, difference: 17.1% (-1.5%, 35.6%), P = 0.0448] and specificity was non-inferior [72.8% vs 66%, difference:6.8% (-3.4%, 17.0%) P = 0.0004]. Diagnostic certainty was significantly higher for women undergoing flurpiridaz PET compared to Tc99m-SPECT (82.4% v 48.9%). PET perfusion image quality was better than Tc99m-SPECT for rest and pharmacological stress images (P < 0.0001). The summed difference score was significantly higher for flurpiridaz (5.3 v 3.5). Radiation exposure was significantly lower for flurpiridaz than same day rest/stress Tc99m-SPECT (6.2 v 11.2 mSv). CONCLUSIONS:This pre-specified secondary analysis of the ARORA study in women, demonstrates high diagnostic accuracy of flurpiridaz PET to detect obstructive CAD. In women, the diagnostic performance of flurpiridaz PET for detection of CAD was significantly higher than with 99mTc-SPECT.

Hospital-wide strategies improve outcomes in STEMI, yet their impact on patients with nonsystem delays (NSD) to primary PCI remains unknown. This study evaluated the effect of a 4-step comprehensive STEMI protocol (CSP) on outcomes in this high-risk population. This observational cohort analysis included STEMI patients with NSD as defined by the ACC National Cardiovascular Data Registry CathPCI Registry v5.0 criteria, which included difficult vascular access, difficulty crossing the culprit lesion, cardiac arrest and/or need for intubation before PCI, patient delays in providing consent for PCI, emergent placement of left-ventricular support device before PCI, and other reasons. Process and outcome metrics were compared before (January, 2011-July, 2014; n = 163) and after (July, 2014-July, 2019; n = 196) CSP implementation. The CSP comprised: (1) emergency department catheterization-laboratory activation; (2) STEMI Safe Handoff Checklist; (3) immediate transfer to an available laboratory; and (4) radial-first PCI. Among 359 patients with NSD, CSP implementation increased pre-PCI guideline-directed medical therapy (57.1%-79.6%, p <0.001) and radial access (16.6%-55.6%, p <0.001), and reduced median door-to-balloon time (132-101 minutes, p = 0.001). Post-CSP patients experienced lower rates of bleeding (22.7%-10.2%, p = 0.002), cardiac arrest (36.2%-23.5%, p = 0.01), circulatory shock (39.9%-24.5%, p = 0.003), and acute kidney injury (30.7%-19.9%, p = 0.03), with more frequent discharge to home (65.0%-78.6%, p = 0.006). In-hospital mortality was similar (14.1% vs 9.2%, p = 0.20). In conclusion, a 4-step CSP improved process metrics and clinical outcomes among STEMI patients with NSD, challenging the notion that outcomes of NSD cohort are unmodifiable and underscoring the importance of system-based interventions in this high-risk cohort.

Background Heart failure (HF) patients may be at risk of developing arrhythmias and conduction disorders. The ADHERE Registry found that approximately 5% of HF patients with preserved or moderately reduced ejection fraction (EF) received a permanent pacemaker (PPM) within 12 months of an incident hospitalization. Objective To quantify new PPM implants in a population of preserved or moderately reduced EF HF patients. Methods The LUX-Dx TRENDS study (NCT04790344) is designed to collect physiologic measurement data in HF patients using an investigational version of the LUX-Dx Insertable Cardiac Monitor (ICM). Patients in NYHA Class II or III HF were enrolled if they had a HF hospitalization or unscheduled IV diuretic therapy in the last 12 months or had elevated natriuretic peptides and were not implanted with any active cardiac implantable electronic device. This preliminary analysis focused on patients with EF >40%. The incidence of new PPM implants within 1 year of enrollment was evaluated; this included single and dual chamber, leadless, and cardiac resynchronization pacemakers. Results There were 429 patients with a baseline EF >40%; the mean follow-up time was 522 days (range: 4-1034), with 292 completing a full year of follow-up. To date, 38 patients were confirmed to have received a PPM with mean time to PPM upgrade of 268 ± 170 days. Of these, 27 (71%) had no prior documented history of bradyarrhythmia. Twenty-eight (28) PPM were implanted within 1 year of enrollment, corresponding to a one-year incident PPM rate of 8.8%. The true rate may be higher as there were 8 additional patients with device upgrades for whom the device type or date of upgrade could not be ascertained. Conclusion In this population of HF patients with preserved or moderately reduced EF, the one-year incidence rate for PPMs was >8%, which is slightly higher than what has been reported for a similar population in the year immediately following hospitalization for HF. These data highlight the sustained risk for developing conduction disorders in patients with HF, and thus the potential utility of long-term arrhythmia monitoring in this population to earlier identify patients at risk.