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. 2021 May;14(5):e007991.
doi: 10.1161/CIRCHEARTFAILURE.120.007991. Epub 2021 May 5.

Framework to Classify Reverse Cardiac Remodeling With Mechanical Circulatory Support: The Utah-Inova Stages

Palak Shah #  1 , Mitchell Psotka #  1 , Iosif Taleb #  2   3 , Rami Alharethi  2 , Mortada A Shams  1   4 , Omar Wever-Pinzon  2   3 , Michael Yin  2   3 , Federica Latta  1   5 , Josef Stehlik  2 , James C Fang  2 , Guoqing Diao  6 , Ramesh Singh  7 , Naila Ijaz  1 , Christos P Kyriakopoulos  2   3 , Wei Zhu  1 , Christopher W May  1 , Lauren B Cooper  2 , Shashank S Desai  2 , Craig H Selzman  2   3 , Abdallah G Kfoury  2 , Stavros G Drakos  2   3
Affiliations

Framework to Classify Reverse Cardiac Remodeling With Mechanical Circulatory Support: The Utah-Inova Stages

Palak Shah et al. Circ Heart Fail. 2021 May.

Abstract

Background: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD.

Methods: The study enrolled consecutive LVAD patients across 4 study sites. A blinded echocardiographer evaluated the degree of structural (LV internal dimension at end-diastole [LVIDd]) and functional (LV ejection fraction [LVEF]) change after LVAD. Patients experiencing an improvement in LVEF ≥40% and LVIDd ≤6.0 cm were termed responders, absolute change in LVEF of ≥5% and LVEF <40% were termed partial responders, and the remaining patients with no significant improvement in LVEF were termed nonresponders.

Results: Among 358 LVAD patients, 34 (10%) were responders, 112 (31%) partial responders, and the remaining 212 (59%) were nonresponders. The use of guideline-directed medical therapy for heart failure was higher in partial responders and responders. Structural changes (LVIDd) followed a different pattern with significant improvements even in patients who had minimal LVEF improvement. With mechanical unloading, the median reduction in LVIDd was -0.6 cm (interquartile range [IQR], -1.1 to -0.1 cm; nonresponders), -1.1 cm (IQR, -1.8 to -0.4 cm; partial responders), and -1.9 cm (IQR, -2.9 to -1.1 cm; responders). Similarly, the median change in LVEF was -2% (IQR, -6% to 1%), 9% (IQR, 6%-14%), and 27% (IQR, 23%-33%), respectively.

Conclusions: Reverse cardiac remodeling associated with durable LVAD support is not an all-or-none phenomenon and manifests in a continuous spectrum. Defining 3 stages across this continuum can inform clinical management, facilitate the field of myocardial plasticity, and improve the design of future investigations.

Keywords: cardiomyopathy; heart failure; left ventricular remodeling; myocardial recovery; ventricular assist device.

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Figures

Figure 1.
Figure 1.. Echocardiographic Measurements at Baseline and After LVAD Implantation
Visual depiction of change in each patient’s left ventricular cavity size and ejection fraction at baseline before LVAD and at follow-up. The blue circles represent the intersection of the patient LVEF and LVIDd at baseline before LVAD and the orange triangles represent the values at follow-up while on LVAD support. The LVIDd is graphed on the x-axis and LVEF on the y-axis. Dashed lines mark left ventricular end-diastolic internal diameter (LVIDd) of 6.0 cm and left ventricular ejection fraction (LVEF) of 40%.
Figure 2.
Figure 2.. Development of Stages for Myocardial Reverse Remodeling with Mechanical Unloading
Flow diagram to assist in categorizing the stages of response to mechanical unloading using baseline and follow-up left ventricular size and function. In the general LVAD population patients are classified as: Responders, LVEF ≥ 40% & LVIDd ≤ 6.0cm (10%),– Partial Responders (31%), and Non-Responders (59%), based on change in ventricular function and structure with ventricular unloading.
Figure 3.
Figure 3.. Slope of Reverse Cardiac Remodeling based on Responder Stage.
Visual depiction of the change in each patient’s left ventricular cavity size on the x-axis (LVIDd) and ejection fraction on the y-axis (LVEF) at baseline before and after mechanical unloading with an LVAD. The circle indicates the baseline LVIDd and LVEF and the arrow tip represents the final LVIDd and LVEF. Each color group represents the three responder categories. The slope of the change in LVEF over the change in LVIDd is provided. Increasing negative numbers suggest more significant reverse remodeling.
Figure 4.
Figure 4.. Time Course for Change in Left Ventricular Function and Structure after LVAD Based on Responder Stage
By comparing the baseline and last follow-up echocardiogram, changes in LVEF and LVIDd were used to categorize LVAD patients into three distinct groups: Responders (blue), Partial Responders (green), and Non-Responders (red). Using serial echocardiography, the change in function (LVEF) and structure (LVIDd) after LVAD implant are depicted by responder category.
Figure 5:
Figure 5:. Conceptual Framework for Clinical Trial Design Incorporating the U-NOVA Reverse Remodeling Stages
Reverse left ventricular remodeling is not an all or none phenomenon and as many other biological phenomena manifests as a continuous spectrum. We describe a new framework to characterize stages of reverse remodeling with mechanical unloading. We identified three distinct HF sub-populations and their cardiac functional and structural response to durable mechanical circulatory support. This framework for grading reverse remodeling allows for heart failure clinicians and investigators to readily recognize the stages of reverse remodeling and identify subpopulations for personalized management. This functional/structural reverse cardiac remodeling staging may also facilitate advancing the field of myocardial plasticity by informing the study design of future clinical and translational investigations. GDMT: Guideline directed medical therapy.
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