ABSTRACT
CONTEXT.: Myocardial fibrosis underpins a number of cardiovascular conditions and is difficult to identify with standard histologic techniques. Challenges include imaging, defining an objective threshold for classifying fibrosis as mild or severe, and understanding the molecular basis for these changes. OBJECTIVE.: To develop a novel, rapid, label-free approach to accurately measure and quantify the extent of fibrosis in cardiac tissue using infrared spectroscopic imaging. DESIGN.: We performed infrared spectroscopic imaging and combined that with advanced machine learning-based algorithms to assess fibrosis in 15 samples from patients belonging to the following 3 classes: (1) patients with nonpathologic (control) donor hearts, (2) patients undergoing transplant, and (3) patients undergoing implantation of a ventricular assist device. RESULTS.: Our results show excellent sensitivity and accuracy for detecting myocardial fibrosis, as demonstrated by a high area under the curve of 0.998 in the receiver operating characteristic curve measured from infrared imaging. Fibrosis of various morphologic subtypes were demonstrated with virtually generated picrosirius red images, which showed good visual and quantitative agreement (correlation coefficient = 0.92, ρ = 7.76 × 10-15) with stained images of the same sections. Underlying molecular composition of the different subtypes was investigated with infrared spectra showing reproducible differences presumably arising from differences in collagen subtypes and/or crosslinking. CONCLUSIONS.: Infrared imaging can be a powerful tool in studying myocardial fibrosis and gleaning insights into the underlying chemical changes that accompany it. Emerging methods suggest that the proposed approach is compatible with conventional optical microscopy, and its consistency makes it translatable to the clinical setting for real-time diagnoses as well as for objective and quantitative research.
Subject(s)
Heart Transplantation , Coloring Agents , Fibrosis , Humans , Microscopy , Tissue DonorsABSTRACT
BACKGROUND: Prevalence of univentricular (1V) anatomy over time and whether 1V anatomy is associated with early death after heart transplant (HTx) among recipients with adult congenital heart disease (ACHD) is unknown. We investigated changes in case-mix over time, 1V vs biventricular (2V) status, and the effect of 1V anatomy on death after HTx among ACHD recipients. METHODS: The Nationwide Inpatient Sample (NIS) was used to identify ACHD HTx recipients in the United States aged 14 years or older from 1993 to 2007, divided into era 1 (1993 to 2000) and era 2 (2001 to 2007). In-hospital death was compared among recipients with 1V and 2V anatomy. Multivariable determinants associated with an increased risk of in-hospital death were sought with logistic regression models. RESULTS: From a national estimate of 509 ACHD recipients, 143 were 1V and 366 were 2V. Overall, 1V in-hospital mortality (23%) was higher than for 2V (8%; p<0.001) and remained associated with in-hospital death after adjustment for other factors (odds ratio, 3.9; 95% confidence interval, 1.29 to 11.74; p=0.02). All 1V diagnoses had higher mortality than all 2V diagnoses. Despite minor fluctuations, the proportion of 1V patients did not increase over time (era 1, 36%; era 2, 30%; p=0.46). CONCLUSIONS: Overall case-mix of ACHD recipients (1V vs 2V) has not changed over time. Initial 1V anatomy increases post-HTx death among ACHD recipients, whereas 2V patients have mortality rates similar to non-CHD recipients. National and international transplant registries should include specific CHD diagnoses because this factor plays such a large role in determining early outcomes.
