Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features
Xingli LiuGuanzhong WangMao-Ping RuiDong FanMingjie ZhangZhenghua ZhuRosario B PerezTony WangLichuan YangLiang LyuJie ZhengGang Wang
0
Citation
46
Reference
10
Related Paper
Abstract:
The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model.The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF < 65% (termed as HFrEF, n = 10) and LVEF ≥ 65% with diastolic dysfunction (termed as HFpEF, n = 10). Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained.No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, p < 0.001), as well as for stress perfusion (2.40 ± 0.34 ml/min/g in healthy controls vs. 1.28 ± 0.24 ml/min/g in HFpEF group, p < 0.01) and corresponding MPR (1.83 ± 0.3 vs. 1.35 ± 0.29, p < 0.01). After adjusting for age, ECV (p = 0.01) and MPR (p = 0.048) still showed significant differences among the three groups.Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology.Keywords:
Dobutamine
Dobutamine is a cardiac inotrope useful in the acute treatment of congestive heart failure. Dobutamine improves cardiac output, decreases pulmonary wedge pressure, and decreases total systemic vascular resistance with little effect on heart rate or systemic arterial pressure. Clinical benefit has been observed to continue for weeks to months following the discontinuation of dobutamine. In addition, tolerance to dobutamine has been observed when infusions last 72 hours or longer. This has led investigators to study the effectiveness of chronic intermittent infusions of dobutamine. Studies utilizing dobutamine doses ranging from 1.5 to 15 μg/kg/min for 4–48 h/wk have shown sustained clinical and hemodynamic improvement in patients suffering from congestive heart failure The mechanism by which dobutamine creates this effect is not entirely known; however, studies suggest dobutamine exerts a physical conditioning effect similar to exercise. Dobutamine infusions have also been associated with morphological and metabolic changes in myocardial tissue consistent with improved myocardial structure and function. The intermittent use of dobutamine may be beneficial in the chronic treatment of congestive heart failure in patients who fail to respond to conventional therapy.
Dobutamine
Cite
Citations (7)
Cardiac magnetic resonance
Apex (geometry)
Cardiac Imaging
Cite
Citations (0)
Objective: To compare the left ventricular ejection fraction on echocardiograph, cardiac magnetic resonance imaging and single-photon emission computed tomography scan in heart failure patients.
Study Design: This was a prospective cross-sectional study.
Place and Duration of Study: Tertiary Cardiac Care Center of Rawalpindi, Pakistan, from Nov 2021 to Apr 2022.
Methodology: This was a prospective cross-sectional study conducted from November 2021 to April 2022 at a tertiary cardiac care center of Rawalpindi. Thirty (n=30) heart failure patients of either gender with reduced ejection fraction were selected by consecutive sampling technique and were analyzed to quantify their left ventricular ejection fraction (LVEF) using Echo, CMR and SPECT scan. All three modalities were used to measure LVEF in these patients and were compared accordingly.
Results: The LVEF measured by Cardiac Magnetic Resonance Imaging, Single Photon Emission Computed Tomography Scan and Echocardiography was in the range of 15% to 67%. The mean LVEF was 37.2±14.2 by CMR, 37.17±14.1 by SPECT and 38±12.3 by Echo. The mean LVEF determined by SPECT was slightly lower while that determined by Echocardiography was slightly higher. The measured p-value of LVEF by the three modalities, however, indicated statistically difference (p-value <0.05).
Conclusion: Although the literature shows diversity in results of these modalities, CMR is considered the standard reference for assessment of LVEF when interpreted by an expert observer. We in our study found that all three modalities are complimentary to each other and can be used interchangeably depending upon the availability of the equipment and reporting expertise of the observers.
Cardiac magnetic resonance
Emission computed tomography
Cite
Citations (0)
During a recent fiscal year, a 243% increase in dobutamine costs--which were associated with increased drug use--was observed at Brigham and Women's Hospital in Boston. As a result of this increase, a drug usage evaluation was concluded to determine: the indications for which dobutamine was being prescribed, whether or not dopamine could be used in place of dobutamine, and any anticipated cost savings realized by targeting dobutamine prescribing. Forty-six consecutive patients who were receiving dobutamine for hypotension, congestive heart failure, or decreased urine output were evaluated during a 3-month study period. The results indicated that dopamine could have been used as initial therapy in the majority of patients. In only 3 patients was dobutamine considered the drug of choice. Furthermore, the institution could have reduced drug costs by more than $50,000 if the use of dobutamine could have been reserved for its most appropriate indications.
Dobutamine
Cite
Citations (1)
Cardiac magnetic resonance
Cite
Citations (11)
Visual estimation of left ventricular ejection fraction (LVEF) is still used in routine clinical practice. However, most of the studies evaluating the agreement between the visually estimated LVEF (ve-LVEF) and quantitatively measured LVEF (qm-LVEF) either have not used appropriate statistical methods or gold standard imaging modality. In this study, we aimed to assess the agreement between the ve-LVEF and qm-LVEF using contemporary statistical methods and cardiac magnetic resonance imaging (CMRI).In 54 subjects who underwent 1.5-T CMRI, echocardiographic images were recorded after the CMRI procedure on the same day. Two independent observers estimated ve-LVEFs on echocardiographic records in a random and blinded fashion, and qm-LVEF was obtained by CMRI. Agreement between the ve-LVEF and qm-LVEF values and intra/interobserver ve-LVEF estimations were assessed using intraclass correlation coefficient (ICC), Bland-Altman analysis, and kappa statistics.There was a high agreement between the ve-LVEF and qm-LVEF (ICC 0.93, 95% confidence interval 0.88-0.96). Bland-Altman analysis also demonstrated a good agreement between ve-LVEF and qm-LVEF with ve-LVEF, on average, being 0.6% lower than that obtained by CMRI (mean -0.6, limits of agreement -10.5 and +9.3). A good agreement was also observed for LVEF categories ≤35%, 36%-54%, and ≥55% (unweighted kappa 0.71, linearly weighted kappa 0.76); and LVEF of <55% and ≥55% (kappa 0.80). Intra/inter observer agreement was good for ve-LVEFs (ICC value 0.96 and 0.91, respectively).Visual approach for LVEF assessment may be used for rapid assessment of left ventricular systolic function in clinical practice, particularly in patients with good image quality.
Cardiac magnetic resonance
Kappa
Bland–Altman plot
Cite
Citations (1)
Cardiac magnetic resonance
Cite
Citations (38)
Cardiac Imaging
Cardiac magnetic resonance
Cite
Citations (14)
Cardiac magnetic resonance
Cite
Citations (0)