Extracellular volume fraction correlates with myocardial stiffness and allows for differentiation between impaired active relaxation and passive stiffness in heart failure with preserved ejection fraction

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) represents a major challenge in modern cardiology. As described previously, in HFpEF comorbidities promote a systemic inflammatory state, leading to diffuse myocardial fibrosis resulting in myocardial stiffening. Gut dysbiosis which is considered as the novel source of chronic systemic inflammation has been actively investigated as the risk factor for the development and aggravation of cardiovascular diseases including heart failure. Cardiac magnetic resonance T1-mapping is a novel tool, which allows noninvasive quantification of the extracellular space and diffuse myocardial fibrosis. Moreover, the extracellular volume (ECV) fraction can be calculated, providing information on the relative expansion of the extracellular matrix, thus being a noninvasive alternative to myocardial biopsy studies. Purpose The research was aimed at investigating the correlation between the left ventricular ECV and gut microbial genera in patients with HFpEF. Methods 42 patients with confirmed HF-pEF (mediana and interquartile range of age 67 [64; 72] years, 47% men, body mass index <35 kg/m2 with no history of myocardial infarction or diabetes mellitus) were enrolled in the study. The patients underwent transthoracic echocardiography with Doppler study, HF-pEF was confirmed according to the recent ESC guidelines (based on E/e' ratio, N-terminal pro-B type natriuretic peptide >125 pg/ml and symptoms of heart failure). The intestinal microbiome was investigated using high-throughput sequencing of bacterial 16S rRNA gene. As the last step of research T1-myocardial mapping with the modified look-locker inversion-recovery protocol (MOLLI) sequence at 1.5 Tesla was performed to assess left ventricular extracellular volume fraction. Results The mean±std in ECV was 31.02±4.4%. The relative abundance (%) of the most prevalent phyla in gut microbiota was 48±22.5 for Firmicutes, 47.4±22.8 for Bacteroidetes and 1.5 [1.5; 2.5] for Proteobacteria. The analysis showed significant negative correlations between ECV and the following bacterial genera: Faecalibacterium (r=−0.35), Blautia (r=−0.43), Lachnoclostridium (r=−0.32). Moreover ECV positively correlated with Holdemania (r=0.4), Victivallis (r=0.38), Dehalobacterium (r=0.38), Enterococcus (r=0.33) and Catabacter (r=0.32). All correlation values with p<0.05. Conclusion We discovered both negative and positive significant correlations between ECV – the non-invasive marker of myocardial fibrosis and several bacterial genera, which may have negative impact on myocardial remodeling in HF-pEF. Funding Acknowledgement Type of funding source: None

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Electrocardiogram-less, free-breathing myocardial extracellular volume fraction mapping in small animals at high heart rates using motion-resolved cardiovascular magnetic resonance multitasking: a feasibility study in a heart failure with preserved ejection fraction rat model

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/s12968-020-00699-9 ◽

2021 ◽

Vol 23 (1) ◽

Cited By ~ 1

Author(s):

Pei Han ◽

Rui Zhang ◽

Shawn Wagner ◽

Yibin Xie ◽

Eugenio Cingolani ◽

...

Keyword(s):

Heart Failure ◽

Volume Fraction ◽

Extracellular Volume ◽

Small Animal ◽

Free Breathing ◽

Extracellular Volume Fraction ◽

Diffuse Myocardial Fibrosis ◽

Small Animals ◽

Preserved Ejection Fraction ◽

Heart Rates

Abstract Background Extracellular volume fraction (ECV) quantification with cardiovascular magnetic resonance (CMR) T1 mapping is a powerful tool for the characterization of focal or diffuse myocardial fibrosis. However, it is technically challenging to acquire high-quality T1 and ECV maps in small animals for preclinical research because of high heart rates and high respiration rates. In this work, we developed an electrocardiogram (ECG)-less, free-breathing ECV mapping method using motion-resolved CMR Multitasking on a 9.4 T small animal CMR system. The feasibility of characterizing diffuse myocardial fibrosis was tested in a rat heart failure model with preserved ejection fraction (HFpEF). Methods High-salt fed rats diagnosed with HFpEF (n = 9) and control rats (n = 9) were imaged with the proposed ECV Multitasking technique. A 25-min exam, including two 4-min T1 Multitasking scans before and after gadolinium injection, were performed on each rat. It allows a cardiac temporal resolution of 20 ms for a heart rate of ~ 300 bpm. Myocardial ECV was calculated from the hematocrit (HCT) and fitted T1 values of the myocardium and the blood pool. Masson's trichrome stain was used to measure the extent of fibrosis. Welch’s t-test was performed between control and HFpEF groups. Results ECV was significantly higher in the HFpEF group (22.4% ± 2.5% vs. 18.0% ± 2.1%, P = 0.0010). A moderate correlation between the ECV and the extent of fibrosis was found (R = 0.59, P = 0.0098). Conclusions Motion-resolved ECV Multitasking CMR can quantify ECV in the rat myocardium at high heart rates without ECG triggering or respiratory gating. Elevated ECV found in the HFpEF group is consistent with previous human studies and well correlated with histological data. This technique has the potential to be a viable imaging tool for myocardial tissue characterization in small animal models.

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Abstract 18283: Left Ventricular STIFFness vs. Fibrosis Quantification by T1 MAPping in Heart Failure With Preserved Ejection Fraction - STIFFMAP-HFpEF

Circulation ◽

10.1161/circ.132.suppl_3.18283 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Karl-Philipp Rommel ◽

Max von Roeder ◽

Thomas Stiermaier ◽

Konrad Latuscynski ◽

Christian Oberueck ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Myocardial Fibrosis ◽

T1 Mapping ◽

Volume Fraction ◽

Extracellular Volume ◽

Left Ventricular ◽

Diffuse Myocardial Fibrosis ◽

Preserved Ejection Fraction ◽

Stiffness Constant

Introduction: Heart Failure with Preserved Ejection Fraction (HFpEF) is an increasing public health problem. To tailor successful treatment strategies it is essential to identify patients’ individual pathologies contributing to HFpEF. Cardiac magnetic resonance (CMR) derived T1-Mapping has been suggested as non-invasive tool to quantify diffuse myocardial fibrosis. Invasive tracings of pressure-volume relations represent the gold-standard for assessing load-independent mechanical diastolic properties of the left ventricle. Hypothesis: Aim of this study was therefore to elucidate the diagnostic performance of T1-Mapping in HFpEF patients by examining the relationship between the extracellular volume fraction (ECV) and invasively measured parameters of diastolic function and to study the potential of ECV to differentiate between different pathomechanisms in HFPEF. Methods: We performed CMR T1-Mapping in 21 patients with HFpEF and 11 patients without heart failure symptoms (further referred to as controls). Pressure volume loops were obtained with a conductance catheter during basal conditions and handgrip exercise. Transient preload reduction was used to extrapolate the diastolic stiffness constant. Results: Patients with HFpEF showed a higher extra cellular volume fraction (p=0.001), an elevated load-independent passive LV stiffness constant - ß (p<0.001) and a longer time constant of active LV-relaxation Tau (p=0.04). ECV correlated well with ß (r =0.75, p <0.001). After multivariate analysis, ECV remained the only independent predictor of ß. Within the HFpEF cohort, patients with ECV over median showed higher left ventricular masses (p=0.04) and a higher LV stiffness (p=0.05). ECV < median identified patients with a prolonged active LV relaxation (p=0.008) and a marked hypertensive reaction to exercise due to a pathologic arterial elastance (p=0.05). Conclusions: Diffuse myocardial fibrosis, assessed by CMR derived T1-Mapping independently predicts invasively measured LV stiffness in HFpEF. In addition, ECV helps to non-invasively distinguish the role of impaired active relaxation and passive stiffness and refines characterization of patients, which represents a prerequisite for any successful therapy in the future.

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Abstract 17263: Pre-Clinical Left Ventricular Myocardial Remodeling in Patients With Friedreich’s Ataxia: A Cardiac MRI Study

Circulation ◽

10.1161/circ.138.suppl_1.17263 ◽

2018 ◽

Vol 138 (Suppl_1) ◽

Author(s):

Karen A Takazaki1 ◽

Thiago Quinaglia A. C. Silva ◽

Alberto Martinez ◽

Tomas Neilan ◽

Ravi SHAH ◽

...

Keyword(s):

Heart Failure ◽

Volume Fraction ◽

Extracellular Volume ◽

Extracellular Volume Fraction ◽

Friedreich’S Ataxia ◽

Left Ventricular ◽

Friedreich's Ataxia ◽

Intracellular Water ◽

Lv Mass ◽

Burn Out

Background: Heart Failure (HF) is the most common cause of death in Friedreich’s ataxia (FRDA), an inherited mitochondrial disease. Myocardial fibrosis is a well-documented histopathological feature among FRDA patients with HF. Objectives: In this study we will investigate the myocardial extracellular volume fraction (ECV) and intracellular water lifetime (τ ic ), using T1-weighted CMR imaging, in a cohort of patients with FRDA without signs of heart failure. We will also investigate whether myocardial tissue phenotyping by CMR can highlight particular characteristics of LV remodeling in FRDA’s cardiomyopathy, beyond those currently assessed with imaging-based classification of disease severity. Methods: Twenty-six FRDA’s patients (age 26.6±9.3 years, 15 women) without signs of HF, and 10 healthy controls (32.6±7.3 years, 5 women) underwent cardiac magnetic resonance (CMR) studies for assessment of left ventricular (LV) function, myocardial T1, late gadolinium enhancement (LGE), extracellular volume fraction (ECV), and intracellular water-lifetime (τ ic ) as marker of cardiomyocyte size. Neurological decline was determined using the FRDA rating scale (FARS 3). Results: FRDA patients had normal LV ejection fraction (LVEF: 67.66±11.4 vs. 63.9±9.0, P=0.311), larger LV mass index (LVMASSi: 61.03±22.1 vs. 45±4.2g/m 2 , P<0.001), and decreased LV end-diastolic volume index (LVEDVi 53.42±12 vs. 75.7±16.1, P=0.002), compared with controls. ECV and τ ic , were increased in FRDA patients (ECV: 0.36±0.05 vs. 0.25±0.02, P<0.0001; τ ic : 0.13±0.07 vs. 0.06±0.03, P=0.001). ECV was positively associated with LV mass-to-volume ratio (r=0.628, P<0.001). FARS 3 correlated positively with disease duration (r=0.669, P<0.001), and negatively with τ ic , (r=0.478, P=0.039). LVMASSi and cardiomyocyte mass-index [(1–ECV)LVMASSi] declined with age, indicating that LV hypertrophy may transition to a “burn-out” phase with LV atrophy. Conclusions: LV hypertrophy in FRDA reflects an expansion of the myocardial interstitium and an increase in cardiomyocyte size. In contrast, the neurological decline was more likely with decreasing cardiomyocyte size, possibly an early sign of myocardial “burn-out” in FRDA.

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