Dataset Information

The E-wave deceleration rate E/DT outperforms the tissue Doppler-derived index E/e' in characterizing lung remodeling in heart failure with preserved ejection fraction.

ABSTRACT:

Background

Diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) may result in pulmonary congestion and lung remodeling. We evaluated the usefulness of major diastolic echocardiographic parameters and of the deceleration rate of early transmitral diastolic velocity (E/DT) in predicting lung remodeling in a rat model of HFpEF.

Methods and results

Rats underwent aortic banding (AoB) to induce pressure overload (PO). Left ventricular hypertrophy fully developed 2 weeks after AoB. At 4 and 6 weeks, the lung weight-to-body weight ratio (LW/BW), a sensitive marker for pulmonary congestion and remodeling, dramatically increased despite preserved fractional shortening, indicating the presence of HFpEF. The time course of LW/BW was well reflected by E/DT, by the ratio of early to late transmitral diastolic velocity (E/A) and the deceleration time of E (DT), but not by the ratio of transmitral to mitral annular early diastolic velocity (E/e'). In agreement, the best correlation with LW/BW was found for E/DT (r?=?0.76; p<0.0001), followed by E/A (r?=?0.69; p<0.0001), DT (r?=?-0.62; p<0.0001) and finally E/e' (r?=?0.51; p<0.001). Furthermore, analysis of receiver-operating characteristic curves for the prediction of increased LW/BW revealed excellent area under the curve values for E/DT (AUC?=?0.98) and DT (AUC?=?0.95), which are significantly higher than that of E/e' (AUC?=?0.82). In a second approach, we also found that the new parameter E/DT correlated well with right ventricular weight index and echocardiographic measures of right ventricular systolic function.

Conclusions

The novel parameter E/DT outperforms the tissue Doppler index E/e' in detecting and monitoring lung remodeling induced by pressure overload. The results may provide a handy tool to point towards secondary lung disease in HFpEF and warrant further clinical investigations.

SUBMITTER: Nguyen TD

PROVIDER: S-EPMC3849461 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

The E-wave deceleration rate E/DT outperforms the tissue Doppler-derived index E/e' in characterizing lung remodeling in heart failure with preserved ejection fraction.

Nguyen T Dung TD Shingu Yasushige Y Schwarzer Michael M Schrepper Andrea A Doenst Torsten T

PloS one 20131203 12

<h4>Background</h4>Diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) may result in pulmonary congestion and lung remodeling. We evaluated the usefulness of major diastolic echocardiographic parameters and of the deceleration rate of early transmitral diastolic velocity (E/DT) in predicting lung remodeling in a rat model of HFpEF.<h4>Methods and results</h4>Rats underwent aortic banding (AoB) to induce pressure overload (PO). Left ventricular hypertrophy fully develo ...[more]

PMID: 24312628

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Project description:INTRODUCTION:The pathophysiology of heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. We aimed to characterize HFpEF compared to heart failure with reduced ejection fraction (HFrEF) and asymptomatic hypertensive or non-hypertensive controls. MATERIALS AND METHODS:Prospective, observational study of 234 subjects (HFpEF n = 140; HFrEF n = 46, controls n = 48, age 73±8, males 49%) who underwent echocardiography, cardiovascular magnetic resonance imaging (CMR), plasma biomarker analysis (panel of 22) and 6-minute walk testing (6MWT). The primary end-point was the composite of all-cause mortality and/or HF hospitalization. RESULTS:Compared to controls both HF groups had lower exercise capacity, lower left ventricular (LV) EF, higher LV filling pressures (E/E', B-type natriuretic peptide [BNP], left atrial [LA] volumes), more right ventricular (RV) systolic dysfunction, more focal and diffuse fibrosis and higher levels of all plasma markers. LV remodeling (mass/volume) was different between HFpEF (concentric, 0.68±0.16) and HFrEF (eccentric, 0.47±0.15); p<0.0001. Compared to controls, HFpEF was characterized by (mild) reductions in LVEF, more myocardial fibrosis, LA remodeling/dysfunction and RV dysfunction. HFrEF patients had lower LVEF, increased LV volumes, greater burden of focal and diffuse fibrosis, more RV remodeling, lower LAEF and higher LA volumes compared to HFpEF. Inflammatory/fibrotic/renal dysfunction plasma markers were similarly elevated in both HF groups but markers of cardiomyocyte stretch/damage (BNP, pro-BNP, N-terminal pro-atrial natriuretic peptide and troponin-I) were higher in HFrEF compared to HFpEF; p<0.0001. Focal fibrosis was associated with galectin3, GDF-15, MMP-3, MMP-7, MMP-8, BNP, pro-BNP and NTproANP; p<0.05. Diffuse fibrosis was associated with GDF-15, Tenascin-C, MMP-2, MMP-3, MMP-7, BNP, proBNP and NTproANP; p<0.05. Composite event rates (median 1446 days follow-up) did not differ between HFpEF and HFrEF (Log-Rank p = 0.784). CONCLUSIONS:HFpEF is a distinct pathophysiological entity compared to age- and sex-matched HFrEF and controls. HFpEF and HFrEF are associated with similar adverse outcomes. Inflammation is common in both HF phenotypes but cardiomyocyte stretch/stress is greater in HFrEF.

Project description:Objective: Accumulating evidence suggested that resveratrol (RES) could protect against adverse cardiac remodeling induced by several cardiovascular diseases. However, the role of RES in the setting of heart failure with preserved ejection fraction (HFpEF) and the underlying mechanisms of its action remain understood. This study was to determine whether RES could ameliorate HFpEF-induced cardiac remodeling and its mechanisms. Methods: In vivo, C57BL/6 mice served as either the sham or the HFpEF model. The HFpEF mice model was induced by uninephrectomy surgery and d-aldosterone infusion. RES (10 mg/kg/day, ig) or saline was administered to the mice for four weeks. In vitro, transforming growth factor β1 (TGF-β1) was used to stimulate neonatal rat cardiac fibroblasts (CFs) and Ex-527 was used to inhibit sirtuin 1 (Sirt1) in CFs. Echocardiography, hemodynamics, western blotting, quantitative real-time PCR, histological analysis, immunofluorescence, and ELISA kits were used to evaluate cardiac remodeling induced by HFpEF. Sirt1 and Smad3 expressions were measured to explore the underlying mechanisms of RES. Results: HFpEF mice developed left ventricular hypertrophy, preserved ejection fraction, diastolic dysfunction, and pulmonary congestion. Moreover, HFpEF mice showed increased infiltration of neutrophils and macrophages into the heart, including increased interleukin (IL)-1β, IL-6, and TNF-α. We also observed elevated M1 macrophages and decreased M2 macrophages, which were exhibited by increased mRNA expression of M1 markers (iNOS, CD86, and CD80) and decreased mRNA expression of M2 markers (Arg1, CD163, and CD206) in HFpEF hearts. Moreover, HFpEF hearts showed increased levels of intracellular reactive oxygen species (ROS). Importantly, HFpEF mice depicted increased collagen-I and -III and TGF-β mRNA expressions and decreased protein expression of phosphorylated endothelial nitric-oxide synthase (p-eNOS). Results of western blot revealed that the activated TGF-β/Smad3 signaling pathway mediated HFpEF-induced cardiac remodeling. As expected, this HFpEF-induced cardiac remodeling was reversed when treated with RES. RES significantly decreased Smad3 acetylation and inhibited Smad3 transcriptional activity induced by HFpEF via activating Sirt1. Inhibited Sirt1 with Ex-527 increased Smad3 acetylation, enhanced Smad3 transcriptional activity, and offset the protective effect of RES on TGF-β-induced cardiac fibroblast-myofibroblast transformation in CFs. Conclusion: Our results suggested that RES exerts a protective action against HFpEF-induced adverse cardiac remodeling by decreasing Smad3 acetylation and transcriptional activity via activating Sirt1. RES is expected to be a novel therapy option for HFpEF patients.

Project description:BackgroundHeart failure with preserved ejection fraction (HFpEF) often coexists with chronic kidney disease (CKD). Exercise intolerance is a major determinant of quality of life and morbidity in both scenarios. We aimed to evaluate the associations between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) with maximal aerobic capacity (peak VO2) in ambulatory HFpEF and whether these associations were influenced by kidney function.MethodsThis single-centre study prospectively enrolled 133 patients with HFpEF who performed maximal cardiopulmonary exercise testing. Patients were stratified across estimated glomerular filtration rate (eGFR) categories (<60 ml/min/1.73 m2 versus ≥60 ml/min/1.73 m2).ResultsThe mean age of the sample was 73.2 ± 10.5 years and 56.4% were female. The median of peak VO2 was 11.0 ml/kg/min (interquartile range 9.0-13.0). A total of 67 (50.4%) patients had an eGFR <60 ml/min/1.73 m2. Those patients had higher levels of NT-proBNP and lower peak VO2, without differences in CA125. In the whole sample, NT-proBNP and CA125 were inversely correlated with peak VO2 (r = -0.43, P < .001 and r = -0.22, P = .010, respectively). After multivariate analysis, we found a differential association between NT-proBNP and peak VO2 across eGFR strata (P for interaction = .045). In patients with an eGFR ≥60 ml/min/1.73 m2, higher NT-proBNP identified patients with poorer maximal functional capacity. In individuals with eGFR <60 ml/min/1.73 m2, NT-proBNP was not significantly associated with peak VO2 [β = 0.02 (95% confidence interval -0.19-0.23), P = .834]. Higher CA125 was linear and significantly associated with worse functional capacity without evidence of heterogeneity across eGFR strata (P for interaction = .620).ConclusionsIn patients with stable HFpEF, NT-proBNP was not associated with maximal functional capacity when CKD was present. CA125 emerged as a useful biomarker for estimating effort intolerance in HFpEF irrespective of the presence of CKD.

Dataset Information

The E-wave deceleration rate E/DT outperforms the tissue Doppler-derived index E/e' in characterizing lung remodeling in heart failure with preserved ejection fraction.

Background

Methods and results

Conclusions

Publications

The E-wave deceleration rate E/DT outperforms the tissue Doppler-derived index E/e' in characterizing lung remodeling in heart failure with preserved ejection fraction.

Similar Datasets

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