Dobutamine stress magnetic resonance imaging for the detection of coronary artery disease in women

The diagnostic capability of DSMR for the detection of haemodynamically relevant, obstructive CAD is independent of gender

Screening of Essential Oil Active Compounds for Manipulation of Rumen Fermentation and Methane Mitigation

The objective of this study was to investigate the effects of 11 active compounds of essential oils (ACEO) on rumen fermentation characteristics and methane production. Two trials were conducted. In trial 1, ACEO (eugenol, carvacrol, citral, limonene, 1,4-cineole, p-cymene, linalool, bornyl acetate, α-pinene, and β-pinene) at a dose of 1,000 μL/L were incubated for 24 h in diluted rumen fluid with a 70:30 forage:concentrate substrate (16.2% crude protein; 36.6% neutral detergent fiber). Three fistulated Holstein cows were used as donors of rumen fluid. The reduction in methane production was observed with nine ACEO (up to 86% reduction) compared with the control (p<0.05). Among these, only limonene, 1,4-cineole, bornyl acetate, and α-pinene did not inhibit volatile fatty acid (VFA) production, and only bornyl acetate produced less methane per mol of VFA compared with the control (p<0.05). In a subsequent trial, the effects on rumen fermentation and methane production of two concentrations (500 and 2,000 μL/L) of bornyl acetate, the most promising ACEO from the first trial, were evaluated using the same in vitro incubation method that was used in the first trial. In trial 2, monensin was used as a positive control. Both doses of bornyl acetate decreased (p<0.05) methane production and did not inhibit VFA production. Positive effects of bornyl acetate on methane and VFA production were more pronounced than the effects of monensin. These results confirm the ability of bornyl acetate to decrease methane production, which may help to improve the efficiency of energy use in the rumen

High spatial resolution myocardial perfusion imaging during high dose dobutamine/atropine stress magnetic resonance using k-t SENSE

PURPOSE: To prospectively evaluate the feasibility and diagnostic accuracy of high spatial resolution myocardial perfusion imaging during high dose dobutamine/atropine stress magnetic resonance (DSMR) for the detection of coronary artery disease (CAD). METHODS AND RESULTS: DSMR-wall motion was combined with perfusion imaging (DSMR-perfusion) in 78 patients prior to clinically indicated invasive coronary angiography. For DSMR-perfusion an in-plane spatial resolution of 1.5×1.5mm(2) was attained by using 8×k-space and time sensitivity encoding (k-t SENSE). Image quality and extent of artifacts during perfusion imaging were evaluated. Wall motion and perfusion data were interpreted sequentially. Significant CAD (stenosis≥70%) was present in 52 patients and involved 86 coronary territories. One patient did not reach target heart rate despite maximum infusion of dobutamine/atropine. Two studies (3%) were non-diagnostic due k-t SENSE related artifacts resulting from insufficient breathhold capability. Overall image quality was good. Dark-rim artifacts were limited to the endocardial border at a mean width of 1.8mm. The addition of DSMR-perfusion to DSMR-wall motion data improved sensitivity for the detection of CAD (92% vs. 81%, P=0.03) and accurate determination of disease extent (85% vs. 66% of territories, P<0.001). There were no significant differences between DSMR-perfusion and DSRM-wall motion regarding overall specificity (83% vs. 87%, P=1) and accuracy (89% vs. 83%, P=0.13). CONCLUSION: High spatial resolution DSMR-perfusion imaging at maximum stress level was feasible, improved sensitivity over DSMR-wall motion for the detection of CAD and allowed an accurate determination of disease extent. Specificity of DSMR-perfusion with k-t SENSE improved compared to prior studies using lower spatial resolution

Influence of left ventricular hypertrophy and geometry on diagnostic accuracy of wall motion and perfusion magnetic resonance during dobutamine stress

The accuracy of DSMR-wall motion is influenced by LV geometry. In patients with concentric remodeling and concentric hypertrophy, additional first-pass perfusion imaging during high-dose dobutamine stress improves the diagnostic accuracy for the detection of coronary artery disease

Coronary Atheroma Regression With Evolocumab in Stable and Unstable Coronary Syndromes

Stephen J. Nicholls, Yu Kataoka, Steven E. Nissen, Francesco Prati, Stephan Windecker, Rishi Puri, Thomas Hucko, Daniel Aradi, Jean-Paul R. Herrman, Renicus S. Hermanides, Bei Wang, Huei Wang, Julie Butters, Giuseppe Di Giovanni, Stephen Jones, Gianluca Pompili, Kathy Wolski, Peter J. Psalti

Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction

Background: The proprotein convertase subtilisin kexin type-9 inhibitor evolocumab produced coronary atheroma regression in statin-treated patients. Objectives The purpose of this study was to determine the effect of evolocumab on optical coherence tomography (OCT) measures of plaque composition. Methods: Patients with a non–ST-segment elevation myocardial infarction were treated with monthly evolocumab 420 mg (n ¼ 80) or placebo (n ¼ 81) for 52 weeks. Patients underwent serial OCT and intravascular ultrasound imaging within a matched arterial segment of a nonculprit vessel. The primary analysis determined the change in the minimum fibrous cap thickness and maximum lipid arc throughout the imaged arterial segment. Additional analyses determined changes in OCT features in lipid-rich plaque regions and plaque burden. Safety and tolerability were evaluated. Results: Among treated patients (age 60.5 9.6 years; 28.6% women; low-density lipoprotein cholesterol [LDL-C], 141.3 33.1 mg/dL), 135 had evaluable imaging at follow-up. The evolocumab group achieved lower LDL-C levels (28.1 vs 87.2 mg/dL; P < 0.001). The evolocumab group demonstrated a greater increase in minimum fibrous cap thickness (þ42.7 vs þ21.5 mm; P ¼ 0.015) and decrease in maximum lipid arc (57.5o vs. 31.4o ; P ¼ 0.04) and macrophage index (3.17 vs 1.45 mm; P ¼ 0.04) throughout the arterial segment. Similar benefits of evolocumab were observed in lipid-rich plaque regions. Greater regression of percent atheroma volume was observed with evolocumab compared with placebo (2.29% 0.47% vs 0.61% 0.46%; P ¼ 0.009). The groups did not differ regarding changes in microchannels or calcium. Conclusions: The combination of statin and evolocumab after a non–ST-segment elevation myocardial infarction produces favorable changes in coronary atherosclerosis consistent with stabilization and regression. This demonstrates a potential mechanism for the improved clinical outcomes observed achieving very low LDL-C levels following an acute coronary syndrome. (Imaging of Coronary Plaques in Participants Treated With Evolocumab; NCT03570697).Stephen J. Nicholls, Yu Kataoka, Steven E. Nissen, Francesco Prati, Stephan Windecker, Rishi Puri, Thomas Hucko, Daniel Aradi, Jean-Paul R. Herrman, Renicus S. Hermanides, Bei Wang, Huei Wang, Julie Butters, Giuseppe Di Giovanni, Stephen Jones, Gianluca Pompili, Peter J. Psalti

Assessment of omecamtiv mecarbil for the treatment of patients with severe heart failure

Importance: Heart failure with reduced ejection fraction is a progressive clinical syndrome, and many patients’ condition worsen over time despite treatment. Patients with more severe disease are often intolerant of available medical therapies. Objective: To evaluate the efficacy and safety of omecamtiv mecarbil for the treatment of patients with severe heart failure (HF) enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) randomized clinical trial. Design, Setting, and Participants: The GALACTIC-HF study was a global double-blind, placebo-controlled phase 3 randomized clinical trial that was conducted at multiple centers between January 2017 and August 2020. A total of 8232 patients with symptomatic HF (defined as New York Heart Association symptom class II-IV) and left ventricular ejection fraction of 35% or less were randomized to receive omecamtiv mecarbil or placebo and followed up for a median of 21.8 months (range, 15.4-28.6 months). The current post hoc analysis evaluated the efficacy and safety of omecamtiv mecarbil therapy among patients classified as having severe HF compared with patients without severe HF. Severe HF was defined as the presence of all of the following criteria: New York Heart Association symptom class III to IV, left ventricular ejection fraction of 30% or less, and hospitalization for HF within the previous 6 months. Interventions: Participants were randomized at a 1:1 ratio to receive either omecamtiv mecarbil or placebo. Main Outcomes and Measures: The primary end point was time to first HF event or cardiovascular (CV) death. Secondary end points included time to CV death and safety and tolerability. Results: Among 8232 patients enrolled in the GALACTIC-HF clinical trial, 2258 patients (27.4%; mean [SD] age, 64.5 [11.6] years; 1781 men [78.9%]) met the specified criteria for severe HF. Of those, 1106 patients were randomized to the omecamtiv mecarbil group and 1152 to the placebo group. Patients with severe HF who received omecamtiv mecarbil experienced a significant treatment benefit for the primary end point (hazard ratio [HR], 0.80; 95% CI, 0.71-0.90), whereas patients without severe HF had no significant treatment benefit (HR, 0.99; 95% CI, 0.91-1.08; P = .005 for interaction). For CV death, the results were similar (HR for patients with vs without severe HF: 0.88 [95% CI, 0.75-1.03] vs 1.10 [95% CI, 0.97-1.25]; P = .03 for interaction). Omecamtiv mecarbil therapy was well tolerated in patients with severe HF, with no significant changes in blood pressure, kidney function, or potassium level compared with placebo. Conclusions and Relevance: In this post hoc analysis of data from the GALACTIC-HF clinical trial, omecamtiv mecarbil therapy may have provided a clinically meaningful reduction in the composite end point of time to first HF event or CV death among patients with severe HF. These data support a potential role of omecamtiv mecarbil therapy among patients for whom current treatment options are limited. Trial Registration: ClinicalTrials.gov Identifier: NCT02929329