Basic Science and Experimental Studies
Left Atrial Reverse Remodeling in Dogs With Moderate and Advanced Heart Failure Treated With a Passive Mechanical Containment Device: An Echocardiographic Study

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Abstract

Background

Assessment of global left ventricular (LV) remodeling is important in evaluating the efficacy of pharmacologic and device therapies for the treatment of chronic heart failure (HF). The effects of pharmacologic or device therapies on global left atrial (LA) remodeling in HF, although also important, are not often examined. We showed that long-term therapy with the Acorn Cardiac Support Device (CSD), a passive mechanical ventricular containment device, prevents or reverses LV remodeling in dogs with HF. This study examined the effects of the CSD on global LA remodeling in dogs with moderate and advanced HF.

Methods and Results

Studies were performed in 24 dogs with coronary microembolization-induced HF. Of these, 12 had moderate HF (ejection fraction, EF 30% to 40%) and 12 advanced HF (EF ≤25%). In each group, the CSD was implanted in 6 dogs and the other 6 served as controls. Dogs were followed for 3 months in the moderate group and 6 months in the advanced HF group. LA maximal volume (LAVmax), LA volume at the onset of the p-wave (LAVp), LA minimal volume (LAVmin), LA active emptying volume (LAAEV), and LA active emptying fraction (LAAEF) were measured from 2-dimensional echocardiograms obtained before CSD implantation and at the end of the treatment period. Treatment effect (Δ) comparisons between CSD-treated dogs and controls showed that CSD therapy significantly decreased LA volumes (ΔLAVmax: 3.33 ± 0.70 vs. –2.87 ± 1.31 mL, P = .002; 7.77 ± 1.76 versus –0.37 ± 0.87 mL, P = .002) and improved LA function (ΔLAAEF: –6.00 ± 1.53 versus 1.85 ± 1.32%, P = .003; –2.39 ± 1.10 versus 3.13 ± 1.66%, P = .02) in the moderate HF and advanced HF groups, respectively.

Conclusions

Progressive LA enlargement and LA functional deterioration occurs in untreated dogs with HF. Monotherapy with the CSD prevents LA enlargement and improves LA mechanical function in dogs with moderate and advanced HF indicating prevention or reversal of adverse LA remodeling.

Section snippets

Experimental Model

The canine model of chronic HF used in this study was previously described in detail.19 Chronic LV dysfunction was produced by multiple sequential coronary microembolizations with polystyrene Latex microspheres (70 to 102 μm in diameter), which result in loss of viable myocardium. The model manifests many of the hemodynamic and neurohormonal sequelae of HF observed in humans including marked and progressive depression of LV systolic and diastolic function, reduced cardiac output, and increased

Results

All dogs entered into the study had baseline angiographic and echocardiographic measures within the range of normality for mongrel dogs in our laboratory. Baseline echocardiographic data for both study groups are shown in Table 1. There were no significant differences in any of the echocardiographic measures obtained at baseline between control dogs and dogs subsequently treated with the CSD. Similarly, there were no significant differences in echocardiographic measure at pretreatment between

LA Reverse Remodeling with CSD Therapy

The present study demonstrates that implantation of the Acorn CSD is effective in preventing LA enlargement and in improving LA mechanical performance in dogs with moderate and advanced HF. This observation is particularly reassuring because the CSD operates by containing the ventricles and preventing progressive LV dilation with no readily apparent theoretical evidence that such a device would favorably affect progressive LA remodeling. The beneficial effects of the CSD on LA remodeling was

Conclusions

The results of the present study indicate chronic CSD therapy, in addition to improving LV function and preventing progressive LV remodeling, also afford considerable benefits on LA function and remodeling. The benefits of CSD therapy on LA function and chamber remodeling appears to be present regardless of the severity of LV dysfunction and, hence severity of HF. The extent to which such benefits of CSD therapy on LA remodeling can lead to reduced risk of adverse cardiovascular events and

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    Supported, in part, by grants from Acorn Cardiovascular, Inc., and by a grant from the National Heart, Lung, and Blood Institute, PO1-HL074237-04.

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