Clinical Investigation
Skeletal Muscle Perfusion During Mechanical Circulatory Support
Contrast Ultrasound Assessment of Skeletal Muscle Recruitable Perfusion after Permanent Left Ventricular Assist Device Implantation: Implications for Functional Recovery

https://doi.org/10.1016/j.echo.2021.12.014Get rights and content

Highlights

  • CEUS perfusion imaging can quantify vascular dysfunction in heart failure.

  • Limb exercise perfusion is associated with symptom reduction after LVAD.

  • Post-LVAD survival tends to be better in those with improvement in muscle perfusion.

Background

In heart failure with reduced ejection fraction (HFrEF), abnormal regulation of skeletal muscle perfusion contributes to reduced exercise tolerance. The aim of this study was to test the hypothesis that improvement in functional status after permanent left ventricular assist device (LVAD) implantation in patients with HFrEF is related to improvement in muscle perfusion during work, which was measured using contrast-enhanced ultrasound (CEUS).

Methods

CEUS perfusion imaging of calf muscle at rest and during low-intensity plantar flexion exercise (20 W, 0.2 Hz) was performed in patients with HFrEF (n = 22) at baseline and 3 months after placement of permanent LVADs. Parametric analysis of CEUS data was used to quantify muscle microvascular blood flow (MBF), blood volume index, and red blood cell flux rate. For subjects alive at 3 months, comparisons were made between those with New York Heart Association functional class I or II (n = 13) versus III or IV (n = 7) status after LVAD. Subjects were followed for a median of 5.7 years for mortality.

Results

Echocardiographic data before and after LVAD placement and LVAD parameters were similar in subjects classified with New York Heart Association functional class I-II versus functional class III-IV after LVAD. Skeletal muscle MBF at rest and during exercise before LVAD implantation was also similar between groups. After LVAD placement, resting MBF remained similar between groups, but during exercise those with New York Heart Association functional class I or II had greater exercise MBF (111 ± 60 vs 52 ± 38 intensity units/sec, P = .03), MBF reserve (median, 4.45 [3.95 to 6.80] vs 2.22 [0.98 to 3.80]; P = .02), and percentage change in exercise MBF (median, 73% [−28% to 83%] vs −45% [−80% to 26%]; P = .03). During exercise, increases in MBF were attributable to faster microvascular flux rate, with little change in blood volume index, indicating impaired exercise-mediated microvascular recruitment. The only clinical or echocardiographic feature that correlated with post-LVAD exercise MBF was a history of diabetes mellitus. There was a trend toward better survival in patients who demonstrated improvement in muscle exercise MBF after LVAD placement (P = .05).

Conclusions

CEUS perfusion imaging can quantify peripheral vascular responses to advanced therapies for HFrEF. After LVAD implantation, improvement in functional class is seen in patients with improvements in skeletal muscle exercise perfusion and flux rate, implicating a change in vasoactive substances that control resistance arteriolar tone.

Section snippets

Study Subjects

The study was approved by the investigational review board at Oregon Health & Sciences University and registered with ClinicalTrials.gov (NCT02105831). Subjects between 18 and 75 years of age with chronic stage D HFrEF and LV ejection fraction ≤ 35% who were referred for LVAD implantation for refractory symptoms between January 2014 and September 2015 were recruited. Exclusion criteria were moderate or greater peripheral arterial disease (claudication, ankle-brachial index < 0.6, history of

Baseline Clinical and Echocardiographic Data

A total of 22 subjects qualified for the study, consented, and underwent LVAD placement with either a HeartMate II (n = 16; Abbott Laboratories, Abbott Park, IL) or a HeartWare (n = 6; Medtronic, Minneapolis, MN) device. The baseline demographic and clinical characteristics of the study population are provided in Table 1. The study population was nearly evenly balanced between nonischemic and ischemic etiologies of HFrEF. The vast majority of subjects had NYHA functional class IV heart failure

Discussion

The inability to meet the oxygen requirements of working muscle during exertion is one of many contributors to exertional fatigue and dyspnea in patients with HFrEF. This deficit is not caused by impaired cardiac output alone. Peripheral vascular structural and functional abnormalities in HFrEF often impair the normal metabolic and shear-mediated increases in vascular conductance during muscle work.1,2 Although reversal of low-output states with LVAD would be predicted to improve peripheral

Conclusion

In summary, our findings provide evidence that exercise-mediated skeletal muscle blood flow is reduced in patients with severe HFrEF and is improved soon after placement of a permanent LVAD in the subgroup of patients who have substantial improvement in function class. Impairment in muscle perfusion during exercise in those with HFrEF occurs from both impaired microvascular flux rate and a near inability to recruit microvascular units. Post-LVAD improvements in perfusion are attributable almost

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  • Cited by (0)

    Drs. Soman and Hodovan contributed equally to this work.

    Dr. Soman was supported by a Fellowship Grant from the Oregon Health & Science University Tartar Trust. Dr. Lindner is supported by grants R01-HL078610, R01-HL130046, and P51-OD011092 from the National Institutes of Health, and grant 18-18HCFBP_2-0009 from NASA.

    Conflicts of interest: None.

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