Left atrial remodeling, hypertrophy, and fibrosis in mouse models of heart failure

Abstract

Left ventricular dysfunction increases left atrial pressures and causes atrial remodeling. In human subjects, increased left atrial size is a powerful predictor of mortality and adverse events in a broad range of cardiac pathologic conditions. Moreover, structural remodeling of the atrium plays an important role in the pathogenesis of atrial tachyarrhythmias. Despite the potential value of the atrium in assessment of functional endpoints in myocardial disease, atrial pathologic alterations in mouse models of left ventricular disease have not been systematically investigated. Our study describes the geometric, morphologic and structural changes in experimental mouse models of cardiac pressure overload (induced through transverse aortic constriction), myocardial infarction and diabetes. Morphometric and histological analysis showed that pressure overload was associated with left atrial dilation, increased left atrial mass, loss of myofibrillar content in a subset of atrial cardiomyocytes, atrial cardiomyocyte hypertrophy, and atrial fibrosis. In mice undergoing non-reperfused myocardial infarction protocols, marked left ventricular systolic dysfunction was associated with left atrial enlargement, atrial cardiomyocyte hypertrophy and atrial fibrosis. Both infarcted animals and pressure overloaded mice exhibited attenuation and perturbed localization of atrial connexin-43 immunoreactivity, suggesting gap junctional remodeling. In the absence of injury, obese diabetic db/db mice had diastolic dysfunction, associated with atrial dilation, atrial cardiomyocyte hypertrophy and mild atrial fibrosis. Considering the challenges in assessment of clinically relevant functional endpoints in mouse models of heart disease, study of atrial geometry and morphology may serve as an important new tool for evaluation of ventricular function.

G protein‐coupled receptor kinase‐2: A potential biomarker for early diabetic cardiomyopathy

“…It also develops changes in cardiac structure and function similar to those in T2DM patients . Recent studies have confirmed that functional and morphological alterations in db/db hearts are consistent with DCM …”

“…16 Recent studies have confirmed that functional and morphological alterations in db/db hearts are consistent with DCM. 17,18 In this study, we aimed to investigate the association of GRK2 with early DCM by estimating the expression of GRKs both in the myocardium of diabetic mice and in the PBMCs of patients with early DCM.…”

Mast cells participate in the development of diastolic dysfunction in diabetic obese mice

“…diabetes, obesity female gender and hypertension. Lepr db/db mice were previously shown to display diastolic dysfunction 13,18,19 and to recapitulate significant features of human HFpEF 14,20 . In the present study, we thoroughly characterized the cardiac microvascular phenotype of these mice, notably, via a transcriptomic analysis.…”

A multicenter study comparing the outcome of catheter ablation of atrial fibrillation between cryoballoon and radiofrequency ablation in patients with heart failure (CRABL‐HF): Study design

“…25 The PV antrum for the PVI in patients with HF may be more thickened compared to that in those without HF because patients with HF have atrial hypertrophy. 15,16 The transmural lesion creation by the PVI may be difficult in patients with HF and the importance of the PVI durability may be emphasized more in those patients.…”

“…13,14 However, the underlying pathophysiology differs between patients with and without HF. 15,16 Further, the fundamental mechanism of catheter ablation differs between CB and RF ablation as well. There have been no randomized controlled trials addressing the differences in the clinical outcomes between CB and RF ablation for the treatment of AF in patients with HF.…”