BackgroundNon-invasive measures that can accurately estimate cardiac output may help identify volume-responsive patients. This study seeks to compare two non-invasive measures (corrected carotid flow time and carotid blood flow) and their correlations with invasive reference measurements of cardiac output. Consenting adult patients (n = 51) at Massachusetts General Hospital cardiac catheterization laboratory undergoing right heart catheterization between February and April 2016 were included. Carotid ultrasound images were obtained concurrently with cardiac output measurements, obtained by the thermodilution method in the absence of severe tricuspid regurgitation and by the Fick oxygen method otherwise. Corrected carotid flow time was calculated as systole time/√cycle time. Carotid blood flow was calculated as π × (carotid diameter)2/4 × velocity time integral × heart rate. Measurements were obtained using a single carotid waveform and an average of three carotid waveforms for both measures.ResultsSingle waveform measurements of corrected flow time did not correlate with cardiac output (ρ = 0.25, 95% CI −0.03 to 0.49, p = 0.08), but an average of three waveforms correlated significantly, although weakly (ρ = 0.29, 95% CI 0.02–0.53, p = 0.046). Carotid blood flow measurements correlated moderately with cardiac output regardless of if single waveform or an average of three waveforms were used: ρ = 0.44, 95% CI 0.18–0.63, p = 0.004, and ρ = 0.41, 95% CI 0.16–0.62, p = 0.004, respectively.ConclusionsCarotid blood flow may be a better marker of cardiac output and less subject to measurements issues than corrected carotid flow time.Electronic supplementary materialThe online version of this article (doi:10.1186/s13089-017-0065-0) contains supplementary material, which is available to authorized users.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Recent studies suggest that pericardial adipose tissue (PCAT) secretes inflammatory factors that contribute to the development of CVD. To better characterize the role of PCAT in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between PCAT and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals. As it was unknown whether PCAT-secreted factors are produced by adipocytes or cells in the supporting stromal fraction, we also sought to identify differentially expressed genes in isolated pericardial adipocytes vs. isolated subcutaneous adipocytes. Using microarray analysis, we found that: 1) pericardial adipose tissue and isolated pericardial adipocytes both overexpress atherosclerosis-promoting chemokines and 2) pericardial and subcutaneous fat depots, as well as isolated pericardial adipocytes and subcutaneous adipocytes, express specific patterns of homeobox genes. In contrast, a core set of lipid processing genes showed no significant overlap with differentially expressed transcripts. These depot-specific homeobox signatures and transcriptional profiles strongly suggest different functional roles for the pericardial and subcutaneous adipose depots. Further characterization of these inter-depot differences should be a research priority.

Introduction: Myocarditis due to immune checkpoint inhibitors (ICIs), a type of cancer immunotherapy, is associated with high morbidity and mortality. The cellular and molecular pathogenesis of ICI myocarditis remains largely unknown. Identification of circulating factors associated with intracardiac pathology may aid new clinical approaches. Hypothesis: We hypothesized that ICI myocarditis is associated with increased abundance of intracardiac immune cells and upregulated inflammatory genes in the heart and serum. Methods: Heart tissue from 13 patients with ICI myocarditis was acquired by endomyocardial biopsy or autopsy; peripheral blood mononuclear cells (PBMCs) were also collected from ten of these patients and eight additional ICI myocarditis patients. Control heart tissue was derived from six hearts declined for transplantation (non-ICI-exposed) and from the biopsy and autopsy of one ICI-treated patient without myocarditis. The 10x Genomics Chromium system was used to generate single-cell RNA sequencing (scRNAseq) data from heart and PBMC specimens. Serum proteins were measured by core lab assay (for troponin T) or by multiplexed Luminex immunoassay. Results: Unbiased clustering of scRNAseq data from 77,071 cells recovered from heart samples revealed 37 cell subsets across 10 cell lineages. Myocarditis heart tissue demonstrated enrichment of T/NK cells (odds ratio 8.3, p=0.0006), B/plasma cells (OR 5.1, p=0.01), and dendritic cells (DCs) (OR 9.2, p=0.006) relative to controls. Circulating DC abundance was decreased in fatal (n=3) versus nonfatal (n=15) myocarditis cases (p=0.008), while intracardiac DC abundance was directly associated with serum troponin T values (p=0.02). The levels of five immunomodulatory factors - IL-15, CXCL9, CCL3, TNFα, and CCL21 - were found to be significantly upregulated transcriptionally in at least one intracardiac cell subset and at the protein level in the serum of myocarditis cases. Conclusions: Fatality status and troponin level associated with intracardiac DC abundance and multiple immunomodulatory genes were upregulated in both the heart and serum in ICI myocarditis. These observations may guide novel diagnostic and therapeutic strategies.

There is increasing interest in using noninvasive ultrasound measures such as carotid blood flow and carotid flow time as predictors of volume responsiveness. While these measures are easy to obtain at the bedside, their correlation with cardiac output (CO) from invasive measures has not been previously demonstrated. This study seeks to compare carotid blood flow and carotid flow time measurements with invasive CO. METHODS: Consenting adult patients at Massachusetts General Hospital cardiac catheterization laboratory undergoing right heart catheterization between Feb and Mar 2016 were invited to participate. Carotid ultrasound images were obtained concurrently with CO both pre-and post-passive leg raise (PLR) maneuvers. CO measurements were obtained by the thermodilution method in the absence of severe tricuspid regurgitation and by the Fick oxygen method in the presence of severe tricuspid regurgitation. PLR was performed using a standardized protocol with a 30 0 foam wedge. Post-PLR measurements were performed within one minute after PLR. Carotid blood flow was calculated as: p x (carotid artery diameter) 2 / 4 x velocity time integral x heart rate. Carotid flow time was calculated as systole time / square-root of cycle time. Pre-and post-PLR parameters were compared using paired t-tests and Wilcoxon signed rank tests, as appropriate. Carotid parameters and CO measurements were correlated using Pearson's correlation coefficients. RESULTS: Forty patients (33 men, 7 women) were included. The mean age of patients was 59 years AE 17 (mean AE SD). PLR did not alter CO (pre vs. post PLR 5.3 AE 1.7 vs. 5.3 AE 1.6 L/min, p¼0.88), carotid blood flow (644.0 AE 308.9 vs. 620.5 AE 256.5 mL/ min, p¼0.50) or carotid flow time (330 AE 56 vs. 338 AE 40 msec, p¼0.23). Carotid blood flow significantly correlated with CO both pre-PLR (r ¼ 0.33, 95% CI 0.02-0.58; p¼0.04) and post-PLR (r ¼ 0.34, 95% CI 0.03-0.59; p ¼ 0.03). Carotid flow time did not correlate with CO either pre-(r ¼ 0.15, 95% CI-0.17 to 0.44, p¼0.37) or post-PLR (r ¼ and 0.22, 95% CI-0.09 to 0.50, p¼0.16, respectively). CONCLUSIONS: The correlation between carotid blood flow and invasive CO was moderate and significant, while carotid flow time did not correlate significantly with CO. CLINICAL IMPLICATIONS: Although the lack of CO increase with PLR in our patient population precluded conclusions regarding fluid responsiveness, our results suggest that carotid blood flow may be a better predictor of CO than carotid flow time.