Transvalvular Mechanical Circulatory Support Reverse Remodels the Ischemic Chronic Failing Heart in an Ovine Model

Figures

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  Figure 1. Ovine Animal Protocol Timeline (A) Following infarction of the mid-left anterior descending artery (LAD) and diagonals (D1, D2), (B) sheep were monitored for 2 months while heart failure developed, at which point they were stratified to receive Impella 5.5 or sham control. After 3 months of unloading or control, necropsy was performed. Magnetic resonance imaging (MRI) and hemodynamics (HD) were assessed at various timepoints. AO = aorta; LA = left atrium; PT = pulmonary trunk; RCX = ramus circumflex.

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  Figure 2. Cardiac Magnetic Resonance 3-Compartment Model and Regional Analysis (A) On each short-axis slice, 3 substrates are defined with infarct, border zone (BZ), and remote segments (when covered by that slice). Regional quantities can be analyzed, such as regional cavity volumes, defined as the volume subtending a certain substrate and other geometrical wall properties, such as substrate mass, wall thickening, and circumferential strain. The BZ is defined as a fix-sized (by angles) region adjacent to infarcted segments to limit including tethering effects between substrates. (B) Final quantities are obtained by summing all slices per substrate.

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  Figure 3. Transvalvular Unloading Improves Left Ventricular Volumes in Chronic Heart Failure Left ventricular volumes and function measured with cardiac magnetic resonance imaging at 2 months postinfarct and 3 months postintervention. Impella-treated hearts showed significantly reduced (A) left ventricular end-diastolic volume (LVEDV) and (B) left ventricular end-systolic volume (LVESV) in comparison to control, without altering the (C) stroke volume (SV) or (D) left ventricular ejection fraction (LVEF). Box plots show the median with 25-75th percentiles (n = 7 control, 7 Impella) ∗P < 0.05, 2-way repeated measures analysis of variance time × treatment interaction. Dots and thin lines represent individual animals for the control (black) and Impella (red) groups over time.

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  Figure 4. Transvalvular Unloading Improves Remote Function and Structure in CHF Regional functional measurements demonstrate a benefit of Impella on (A) regional ejection fraction (EF), (B) wall thickening, (C) circumferential end-systolic strain, (D) end-diastolic (ED) wall stress, and (E) end-systolic (ES) wall stress in the remote zone in the control and Impella groups. Box plots show the median with 25-75th percentiles (n = 7 control, 7 Impella) ∗P < 0.05, 2-way repeated measures analysis of variance time × treatment interaction. Dots and thin lines represent individual animals for the control (black) and Impella (red) groups over time.

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  Figure 5. Transvalvular Unloading Reduces Cardiomyocyte Hypertrophy in Chronic Heart Failure Compensating hypertrophy occurs in control animals but not in Impella-supported animals, as demonstrated by (A) wall volume of the remote zone and (B) myocyte hypertrophy. Representative image of the remote myocardium of a (C) control animal and (D) a pump-supported animal at ×400 magnification. Note the relatively lower number of nuclei (both of cardiomyocytes and interstitial cells) in the control frame caused by cardiomyocyte hypertrophy, and the relatively higher number of nuclei (both of cardiomyocytes and interstitial cells) in the pump-supported frame caused by reverse remodeling. Box plots show the median with 25-75th percentiles (n = 7 control, 7 Impella) ∗P < 0.05, 2-way repeated measures analysis of variance time × treatment interaction (A), Student’s t-test (B).