Mechanical unloading related to left ventricular assist devices (LVAD) substantially improved myocardial structure, and systolic and diastolic function in patients with both ischemic and nonischemic cardiomyopathy, according to research published in the Journal of the American College of Cardiology.1

LVADs have been used to manage patients with advanced heart failure who are nonresponsive to traditional therapies, improving symptoms, exercise tolerance, and survival. In some cases, patients can even experience reverse remodeling and substantial improvement in myocardial function. If LVAD-associated mechanical unloading of the failing heart can be harnessed as a potential therapeutic strategy, patients may be able to avoid heart transplantation altogether.2-6

Researchers from the Utah Transplantation Affiliated Hospitals Cardiac Transplant Program in Salt Lake City sought to determine the effect of ischemic cardiomyopathy heart failure on LVAD-associated improvement of cardiac structure and function with patients who had nonischemic cardiomyopathy as a control group.


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A total of 154 patients with end-stage cardiomyopathy who had implantation of a continuous-flow LVAD as bridge therapy to transplantation or as destination therapy were enrolled in the prospective study. The researchers excluded patients with acute forms of heart failure, including acute myocardial infarction (MI), acute myocarditis, and post-cardiotomy cardiogenic shock. Patients with ischemic cardiomyopathy were older (mean age: 63 years) and had higher prevalence of diabetes and hypertension compared to the nonischemic cardiomyopathy patients (mean age: 52 years).

By 6 months, left ventricular ejection fraction (LVEF) increased from 20% to 24% in patients with ischemic cardiomyopathy (P =.03) and by 9 months, LVEF increased from 17% to 27% in patients with nonischemic cardiomyopathy (P <.01). When supported with an LVAD for 6 months or longer, 5% of patients with ischemic cardiomyopathy and 21% of patients with nonischemic cardiomyopathy achieved an LVEF ≥40% (P =.034).

Left ventricular end-diastolic and end-systolic volumes also decreased in both groups as soon as 30 days after LVAD implantation. Both groups also experienced a decrease in LV mass index (ischemic cardiomyopathy: 133 g/m2 to 92 g/m2 and nonischemic cardiomyopathy: 135 g/m2 to 95 g/m2; P <.01 for both comparisons) at 1-year post-implantation.

The maximum LVEF values reached in both groups were not significantly different after adjustment for baseline LVEF (ischemic cardiomyopathy adjusted mean: 25%; 95% confidence interval [CI], 22%-28% and nonischemic cardiomyopathy adjusted mean: 28%; 95% CI, 25%-30%; P =.14).

LVAD speed decreased resulting in a reduced flow and increased LV loading, as confirmed by turn-down echocardiographic studies. In addition, LV structure and systolic function improvements were maintained in both groups while under increased loading conditions.

While the ischemic cardiomyopathy group was less likely to experience sustained recovery compared to the nonischemic cardiomyopathy group, the difference between them did not reach statistical significance (unadjusted odds ratio [OR]: 0.67; 95% CI, 0.22-2.04; P= .49 and OR: 0.77; 95% CI, 0.22-2.69; P =.068).

“The prospective design of our study and the use of serial post-LVAD hemodynamic and echocardiographic monitoring allowed us to more accurately assess the time course and true incidence of myocardial functional and structural improvement in ICM [ischemic cardiomyopathy] and NICM [nonischemic cardiomyopathy],” the researchers wrote. “We also observed that the improvement in myocardial function was not an ‘all or none’ phenomenon but rather a continuum, similar to other biological phenomena.”

Further studies are necessary to investigate the ischemic and nonischemic cardiomyopathy-specific characteristics that may help predict long-lasting cardiac recovery after LVAD explantation.

Study Limitations

  • LVAD turn-down studies as reliable predictors of long-term myocardial recovery sustainability have not been established.
  • Observations at each prespecified time point decreased as patients either died or were transplanted. 
  • Patients were not assigned to standard heart failure drug therapy vs no drug therapy so the researchers were unable to determine potential contributions of medical therapy during LVAD support to the observed degree of cardiac improvement.
  • Routine cardiopulmonary testing was not included, which means the researchers could not correlate structural and functional changes with exercise response and peak oxygen consumption.

Disclosures: Dr Stehlik has received research support from St. Jude Medical as well as speaker honoraria from St. Jude and Heartware. Dr Drakos has received research support from Abiomed and is a consultant for Heartware.

References

  1. Wever-Pinzon J, Selzman CH, Stoddard G, et al. Impact of ischemic heart failure etiology on cardiac recovery during mechanical unloading. J Am Coll Cardiol. 2016;68(16):1741-1752. doi:10.1016/j.jacc.2016.07.756.
  2. Birks EJ, Tansley PD, Hardy J, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006;355:1873-1884.
  3. Matsumiya G, Monta O, Fukushima N, et al. Who would be a candidate for bridge to recovery during prolonged mechanical left ventricular support in idiopathic dilated cardiomyopathy? J Thorac Cardiovasc Surg. 2005;130:699-704.
  4. Birks EJ, George RS, Hedger M, et al. Reversal of severe heart failure with a continuous-flow left ventricular assist device and pharmacological therapy: a prospective study. Circulation. 2011;123:381-390.
  5. Patel SR, Saeed O, Murthy S, et al. Combining neurohormonal blockade with continuous-flow left ventricular assist device support for myocardial recovery: a single-arm prospective study. J Heart Lung Transplant. 2013;32:305-312.
  6. Frazier OH, Baldwin AC, Demirozu ZT, et al. Ventricular reconditioning and pump explantation in patients supported by continuous-flow left ventricular assist devices. J Heart Lung Transplant. 2015;34:766-772.