Regional Distribution of Fluorine-18-Flubrobenguane and Carbon-11-Hydroxyephedrine for Cardiac PET Imaging of Sympathetic Innervation.

OBJECTIVES: The aim of this study was to investigate the regional distribution of novel 18F-labeled positron emission tomographic (PET) tracer flubrobenguane (FBBG) (whose longer half-life could enable more widespread use) to assess myocardial presynaptic sympathetic nerve function in humans in comparison to [11C]meta-hydroxyephedrine (HED). BACKGROUND: The sympathetic nervous system (SNS) is vitally linked to cardiovascular regulation and disease. SNS imaging has shown prognostic value. HED is the most commonly used PET tracer for evaluation of sympathetic function in humans, but widespread clinical use is limited because of the short half-life of 11C. METHODS: A total of 25 participants (n = 6 healthy; n = 14 ischemic cardiomyopathy, left ventricular [LV] ejection fraction [EF] = 34 ± 5%; and n = 5 nonischemic cardiomyopathy, EF = 33 ± 3%) underwent 2 separate PET imaging visits 8.7 ± 7.6 days apart. On 1 visit, participants underwent dynamic HED PET imaging. On a different visit, participants underwent dynamic FBBG PET imaging. The order of testing was random. HED and FBBG global innervation (retention index [RI] and distribution volume [DV]) and regional denervation (% nonuniformity) were quantified to assess regional presynaptic sympathetic innervations. RESULTS: FBBG RI (r2 = 0.72; ICC = 0.79; p < 0.0001), DV (r2 = 0.62; ICC = 0.78; p < 0.0001), and regional denervation (r2 = 0.97; ICC = 0.98; p < 0.0001) correlated highly with HED. Average LV RI values were highly similar between HED (7.3 ± 2.4%/min) and FBBG (7.0 ± 1.7%/min; p = 0.33). Post-hoc analysis did not reveal any between-tracer differences on a regional level (17-segment), suggesting equivalent regional distributions in both patients with and without ischemic cardiomyopathy. CONCLUSIONS: FBBG and HED yield equivalent global and regional distributions in both patients with and without ischemic cardiomyopathy. 18F-labeled PET tracers, such as FBBG, are critical for widespread distribution necessary for multicenter clinical trials and to maximize patient impact.

Correction to: PET imaging of sympathetic innervation with [18F]Flubrobenguane vs [11C]mHED in a patient with ischemic cardiomyopathy.

At time of initial publication, the USAN Council had assigned the generic name for LMI1195 as Flurobenguan. However, the Council has since changed and finalized this compound name as Flubrobenguane which is recommended as the generic name to be used in the future.

Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study.

BACKGROUND: Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6-8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics. METHODS AND RESULTS: Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11C-acetate and 11C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷Kmono), where Kmono is the monoexponential function fit to the myocardial 11C-acetate time-activity data, reflecting oxidative metabolism. Presynaptic sympathetic nerve function was measured with the use of the 11C-hydroxyephedrine retention index. CPAP significantly increased hydroxyephedrine retention versus no CPAP (Δretention: +0.012 [0.002, 0.021] versus -0.006 [-0.013, 0.005] min(-1); P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index>20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05). CONCLUSIONS: In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00756366.

Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound.

OBJECTIVES: This study was designed to report the clinical and angiographic correlates of plaque rupture detected by intravascular ultrasound (IVUS). BACKGROUND: Acute coronary syndromes result from spontaneous plaque rupture and thrombosis. METHODS: We report 300 plaque ruptures in 257 arteries in 254 patients. Plaque ruptures were detected during pre-intervention IVUS. Standard clinical, angiographic, and IVUS parameters were collected and/or measured. One lesion per patient was analyzed. RESULTS: Multiple ruptures were observed in 39 of 254 patients (15%), 36 in the same artery. Plaque rupture occurred not only in patients with unstable angina (46%) or myocardial infarction (MI, 33%), but also stable angina (11%) or no symptoms (11%). The tear in the fibrous cap could be identified in 157 of 254 patients; 63% occurred at the shoulder of the plaque and 37% in the center of the plaque. Thrombi were more common in patients with unstable angina or MI (p = 0.02) and in multiple ruptures (p = 0.04). The plaque rupture site contained the minimum lumen area (MLA) site in only 28% of patients; rupture sites had larger arterial and lumen areas and more positive remodeling than MLA sites. Intravascular ultrasound plaque rupture strongly correlated with complex angiographic lesion morphology: ulceration in 81%, intimal flap in 40%, thrombus in 7%, and aneurysm in 7%. CONCLUSIONS: Plaque ruptures occur with varying clinical presentations, strongly correlate with angiographic complex lesion morphology, may be multiple, and usually do not cause lumen compromise.

Incidence, morphology, angiographic findings, and outcomes of intramural hematomas after percutaneous coronary interventions: an intravascular ultrasound study.

BACKGROUND: Intramural hematomas during percutaneous coronary intervention (PCI) have not been well studied. METHODS AND RESULTS: We used intravascular ultrasound to determine the incidence, morphology, and clinical features of post-PCI intramural hematomas. In 905 patients with 1025 consecutive native coronary artery, non-in-stent restenosis lesions undergoing PCI, 72 hematomas were detected in 69 arteries in 68 patients. The incidence of intramural hematomas per artery was 6.7% (69 of 1025); 36% (26 of 72) involved the proximal reference artery, 18% (13 of 72) were confined to the lesion, and 46% (33 of 72) involved the distal reference artery. The entry site from the lumen into the hematoma was identified in 86% of hematomas (62 of 72) and had the appearance of a dissection into the media. Conversely, a re-entry site was identifiable in only 8% (6 of 72). The axial extension of the hematoma was distal in 63% and proximal in 37%. In 60% of the hematomas (42 of 72) the angiogram had the appearance of a dissection; in 11% (8 of 72), it appeared to be a new stenosis; and in 29% (22 of 72), no significant abnormality was detected. Non-Q-wave myocardial infarctions occurred in 26% of patients (17 of 65). In 3 patients, the creatine kinase-MB was not measured during the hospital stay. Repeat revascularization occurred in 2 patients in-hospital, 2 additional patients at 1 month, and 8 additional patients at 1 year. There were 3 sudden deaths at 1 year. CONCLUSIONS: Intravascular ultrasound identified intramural hematomas after 6.7% of PCIs. The mechanism appeared to be a dissection into the media where blood accumulated because of a lack of re-entry. A third of ultrasound-identified hematomas showed no angiographic abnormalities. There was a high rate of non-Q-wave myocardial infarction, need for repeat revascularization, and sudden death in patients with hematomas.