Inotrope-Dependent Heart Failure Patients Who Are Ineligible for Transplantation Benefit from Long-Term Mechanical Circulatory Support

August 22, 2007 By Erin Lord [mailto:elord@perfuse.org]

Boston, MA, USA: Inotrope-dependent heart failure patients who are not transplant candidates may obtain a significant survival advantage from long-term mechanical circulatory support, according to results of the INTrEPID (Investigation of Nontransplant-Elegible Patients who are Inotrope Dependent) trial, published this week in the Journal of the American College of Cardiology [1].

The INTrEPID trial was a nonrandomized clinical trial conducted in 13 sites in the United States and Canada that had experience implanting the Novacor Left Ventricular Assist Device (LVAD) as a temporary bridge to sustain patients until cardiac transplantation. Adults with an ejection fraction of < 25%, inotrope-dependent stage D heart failure, New York Heart Association (NYHA) functional class IV symptoms for ≥ 3 months prior to enrollment, and who were ineligible for cardiac transplantation were considered for enrollment. Patients were not considered if there was a contraindication to chronic anticoagulation or if the body surface area was < 1.5 m².

Fifty-five patients were qualified to receive a Novacor LVAD, but 14 patients preferred not to receive one, and the device was unavailable to 4 patients due to a lack of financial resources. The 18 patients who did not receive a LVAD became the control arm of the trial and were administered optimal medical therapy (OMT). The LVAD and OMT patients were well matched on most baseline characteristics and disease severity measures. However, the OMT patients had a higher blood urea nitrogen than the LVAD patients (60 ± 34.0 mg/dl vs. 41 ± 25.9 mg/dl; p = 0.02), and lower serum sodium (128 ± 8.0 mmol/dl vs. 134 ± 4.3 mmol/dl; p < 0.001).

Rogers et al found that patients in the LVAD group had superior survival rates when compared with patients in the OMT group at 6 months (46% vs. 22%; p = 0.03) and at 12 months (27% vs. 11%; p = 0.02). Stroke (34%) and infection (24%) accounted for most of the deaths in the LVAD group, whereas cardiovascular dysfunction (primarily heart failure) was the only cause of death among the OMT group. Five patients in the LVAD group and 1 patient in the OMT group improved sufficiently and received a cardiac transplant.

In terms of adverse effects, bleeding was more common in the LVAD group and was most frequently seen during the perioperative period, whereas cardiovascular dysfunction and renal dysfunction were more commonly seen in the OMT group. During the study, 62% of LVAD patients and 11% of OMT patients experienced TIA or a stroke. In the OMT group, patients experienced no improvement in NYHA functional class. On the contrary, 85% of the patients in the LVAD group had either minimal or no heart failure symptoms at the time of the last assessment.

One limitation of the study is that it was nonrandomized. Because of this trial design, it is possible that either investigational or institutional bias influenced the patients to continue with medical therapy instead of receiving a LVAD. To date, only one other trial has demonstrated the value of mechanical circulatory support in a similar study population [2]. Also, it is possible that the differences in baseline BUN and serum sodium among the two arms of the study affected the outcome of the trial in ways that are difficult to measure.

The enrollment criteria of the INTrEPID trial identified a group of patients that were critically ill and had an extremely poor prognosis. Rogers et al speculate that the benefits of mechanical circulatory support may be greater in a population with less advanced cardiac disease, but further research needs to be done on the topic.

References

Joseph G. Rogers; Javed Butler; Steven L. Lansman; Alan Gass; Peer M. Portner; Michael K. Pasque; Richard N. Pierson III. Chronic Mechanical Circulatory Support for Inotrope-Dependent Heart Failure Patients Who Are Not Transplant Candidates: Results of the INTrEPID Trial. Journal of the American College of Cardiology. 21 August 2007. Volume 50, Issue 8: 741-747

Rose EA, Gelijns AC, Moskowitz AJ, et al., Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) Study Group. Long-term mechanical left ventricular assistance for end-stage heart failure. N Engl J Med 2001; 345:1435-43