Bernhard Unsoeld

Does CircuLite Synergy assist device as partial ventricular support have a place in modern management of advanced heart failure

The discrepancy between the number of patients on the waiting list and available donor hearts has led to the successful development of left ventricular assist devices (LVAD) as a bridge to transplantation. The conventional LVADs are designed to provide full hemodynamic support for the end-stage failing heart. However, full-support LVAD implantation requires major surgery, sternotomy and cardiopulmonary bypass in majority of cases. The Synergy Micro-pump is the smallest implantable LVAD and provides partial flow support up to 3 l/min. It was shown that early intervention with this device can provide substantial benefits to patients with severe heart failure not yet sick enough for a full-support LVAD. Due the small dimensions it can be implanted without cardiopulmonary bypass or a sternotomy. The purpose of this article is to review the clinical use of the Synergy Micro-pump as partial hemodynamic support.

First Experience With the Synergy Micro-Pump in Patients in INTERMACS Class 1–2 as a Bridge to Transplantation: Pushing the Limits?

The Synergy Micro-pump is the smallest implantable left ventricular assist device (LVAD) and provides partial flow support up to 4.25 L/min. It was shown that early intervention with this device can provide substantial benefits to patients with severe heart failure not yet sick enough for a full-support LVAD. However, as it can be inserted via small incisions with no need for sternotomy or cardiopulmonary bypass, it might be beneficial for selected high-risk patients. The aim of this study was to evaluate the efficacy of the Synergy Micro-pump in patients in INTERMACS class 1-2. From February 2012 to August 2013, 13 patients with severe heart failure were supported with the Synergy Pocket Micro-pump. Patients were divided into two groups according to INTERMACS class: the high-risk group (INTERMACS class 1-2) and the low-risk group (INTERMACS class 3-4). There were seven patients in INTERMACS class 1-2 and six in INTERMACS class 3-4. Patient demographics, perioperative characteristics, and postoperative outcomes were compared. There were no statistically significant differences in patient demographics, and mean support time was 108 ± 114 days in the high-risk group and 238 ± 198 days in the low-risk group. Also, there were no significant differences in perioperative characteristics or in the rate of postoperative adverse events. The overall survival was comparable between the two groups (one late death in each group, log-rank P = 0.608). Two patients from the high-risk group were upgraded to a full-support LVAD (P = 0.462) after 65 ± 84.9 days of mean support. One patient from the high-risk group and two patients from the low-risk group were successfully transplanted (P = 0.559). The use of the Synergy Micro-pump in INTERMACS 1-2 patients is feasible and is associated with similar postoperative outcome as in patients in INTERMACS 3-4. Carefully selected patients with severe heart failure could benefit due to the small size of the pump; however, further studies and medium-term follow-up are required.

Inhibition of PI3K improves contractility in alpha1-adrenergically stimulated myocardium

Recent studies have demonstrated that phosphoinositide 3-kinases (PI3Ks) play a fundamental role in regulating myocardial contractility. However, even though alpha1-adrenergic receptor stimulation is known to activate PI3Ks, the impact of this pathway on the inotropic effects of alpha1-stimulation is unclear. Isolated rabbit ventricular myocytes were preincubated with the PI3K inhibitor wortmannin (WM, 0.1 micromol/L). The alpha1 agonist phenylephrine (PE, 10 micromol/L) induced a significantly stronger increase in contractility in WM-treated versus control myocytes (Fractional shortening in percent of resting cell length: 6.14+/-0.33 percent; n=26 versus 4.85+/-0.33 percent; n=26, P less than 0.05). Furthermore, pretreatment with WM significantly increased the positive inotropic effect of PE in intact muscle strips from rabbit hearts. Mechanistically, we demonstrate that in WM-treated myocytes PE increased phospholamban (PLN) phosphorylation and intracellular Ca2+ transients to a significantly greater extent than in control myocytes. In summary, this is the first study to demonstrate that inhibition of PI3K by increasing PLN phosphorylation and Ca2+ transients significantly improves contractility in alpha1-adrenergically stimulated myocardium. This may have clinical implications for the treatment of decreased cardiac function in acute heart failure.