Slaughter et al 2009: Continuous-flow LVADs

Slaughter MS, et al; HeartMate II Investigators. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009 Dec 3;361(23):2241-51. doi: 10.1056/NEJMoa0909938. Epub 2009 Nov 17. PubMed PMID: 19920051.

• Are continuous flow LVADs more efficacious than pulsatile flow LVADs in patients with heart failure refractory to medical therapy?

TYPE OF STUDY

• Randomised unblinded prospective trial

POPULATION

• 200 patients with advanced heart failure were enrolled

Inclusion criteria:

• left ventricular ejection fraction of less than 25%
• a peak oxygen consumption of less than 14 ml/ kg/min, or less than 50% of the predicted value; and
• New York Heart Association (NYHA) class IIIB or IV symptoms for at least 45 of the 60 days before enrollment or dependence on an intraaortic balloon pump for a period of 7 days or inotropes for a period of at least 14 days before enrollment

Exclusion criteria

• irreversible, severe renal, pulmonary, or hepatic dysfunction or active infection

INTERVENTIONS/ COMPARISONS

• Patients were randomised to either pulsatile flow (PF) or continuous flow (CF) on a 1:2 ratio.

OUTCOMES

Primary outcome

• The primary outcome measure was a composite endpoint of survival at 2 years, free of disabling stroke and reoperation.
• 46% of CF LVAD group reached primary endpoint vs 11% of PF LVAD group (95% CI 0.27-0.54, p<0.001)
• continuous-flow left ventricular assist devices were replaced at a rate of 6 events per 100 patient-years, almost one eighth the incidence seen with the pulsatile-flow device, and was mainly required because of damage to the percutaneous lead. 

Secondary outcomes

• Overall survival and adverse events (including stroke, bleeding, reoperation, sepsis) favoured continuous flow VADs over pulsatile flow VADs. There was no significant difference in rates of strokes, but decreased rates of replacement and infection were seen in the continuous flow VAD group.
• There was a notable functional improvement in both groups (measured by NYHA class, 6 minute walk test, QoL questionnaire) which was not associated with the type of device therapy.
• At 2 years only 2/59 patients had a pulsatile flow LVAD still in situ (18 of original PF LVAD group had been replaced with CF LVAD device)
• 1.7 years median duration of CF LVAD therapy versus 0.6 years median for PF LVAD therapy.

Strengths

• Clear outcome measures
• adequately powered
• clearly comparable groups at baseline
• good adverse event data
• adequate follow up (2 year period)
• survival rates of pulsatile flow VADs in this study were similar to those of the previous REMATCH study

Limitations

• Unblinded
• some irregularities in randomisation
• not generalisable (no of patients screened for entry not reported)
• potential for reporting bias of functional outcomes and quality of life outcomes due to lack of blinding
• the composite outcome primarily reflected decreased rates of reoperation in patients with continuous flow VADs, rather than strokes
• data analysed by LVAD manufacturer (Thoratec) and study investigators had received grant support and/ or fees from VAD manufacturers

• “Pulsatile flow – is no go… Continuous flow – that’s the show”
• Provision of a continuous-flow left ventricular assist device, compared with a pulsatile device, significantly improved the probability of survival free from stroke and device failure at 2 years in patients with advanced heart failure.
• Both types of LVAD significantly improved this patient group’s quality of life and functional capacity.