News
"When patients are on the cusp of inotrope dependence [before they reach level 3], I start to think about implanting," said Dr. Jeffrey J. Teuteberg, a cardiologist and associate director of the cardiac transplant program at the University of Pittsburgh. "It’s nice to get patients who are pre–inotrope dependent – profile 4, 5, or 6 – but are symptom limited and quality of life limited. For destination therapy, you want patients with function and good quality of life. Mechanical support provides more than just improved survival; it also reduces adverse events and raises quality of life."
Dr. Jeffrey J. Teuteberg
"For level 2 patients, there is no question that an LVAD as bridge to transplant is better than continued medical treatment," said Dr. Taylor. "For level 3 patients, it’s a little trickier, but I think the majority would say that if a patient is stable and inotropic dependent, use an LVAD unless you believe a transplant will occur quickly. An LVAD would reduce the risk for developing cardiogenic shock. The patient who does the best with an LVAD is the one who is [relatively] healthy when implanted, but the patient who needs it most is the one who is literally dying."
"Everyone knows that if you take patients who are sicker [for LVADs], you’ll have trouble reaching 80% survival after 2 years. But there is not yet enough confidence in the treatment to extend it to INTERMACS level 4, 5, or 6 patients," said Dr. Kirklin. "That’s where the big potential is. The action currently is in INTERMACS 2 and 3. For patients who are INTERMACS 3, there is no question that if they can’t get a transplant they need a VAD. The sweet spot will be patients at INTERMACS 4."
The INTERMACS registry numbers show that the field is currently stuck when it comes to INTERMACS levels, with the greatest number of LVADs going into level 2 patients, who received 34% of U.S LVADS during January-March 2012. The 34% level in early 2012 was down from 38% of LVAD recipients in 2011 and 47% in 2010, but growth in less-severe levels has been slow. At the start of 2012, 30% of LVAD recipients were at level 3, a small increase from the 27% rate in 2011 and 2010. Level 4 patients constituted 14% of LVAD recipients in early 2012, essentially unchanged from the prior 2 years, and level 5, 6, or 7 patients have consistently been a small slice of the U.S. LVAD pie, roughly 5% of recipients each year.
Beyond the INTERMACS Level
Heart failure specialists now recognize that INTERMACS level tells just part of the story.
"INTERMACS profiles depend on heart failure symptoms but not comorbidities. Severe diabetes, obstructive pulmonary disease, cardiorenal syndrome, chronic malnourishment, morbid obesity, and other factors all fall outside the INTERMACS profile criteria," said Dr. Kirklin.
He and his associates are formulating a risk assessment equation that will take comorbidities into account for a more global patient assessment. The most recently published INTERMACS registry analysis, which he first authored using data through the end of June 2011 with a total of 4,366 patients who received left ventricular support since 2006 (J. Heart Lung Transplant 2012;31:117-26), identified several comorbidity markers that each significantly linked with increased mortality. For example, a 1-unit increase in bilirubin linked with a 10% boost in mortality, a 1-unit increase in creatinine raised mortality by 16%, and a 0.5-unit increase in body surface area linked with a 48% rise in deaths. One of the strongest risk factors was being at INTERMACS level 1, which linked with a more-than-threefold higher mortality rate.
But more work must be done before the risk assessment formula is ready for clinical use. Right now, the formula "is not very reliable yet, because the maximum patient follow-up is 2 years. We need a little more follow-up," Dr. Kirklin said.
Growing the LVAD Numbers
Further growth in LVAD placements will happen on two fronts: broader use in patients at INTERMACS levels 2 and 3, and possibly level 4, where a strong consensus exists for LVAD support; and new evidence to document efficacy and safety in patients with less-severe disease at INTERMACS levels 4, 5, 6, and 7.
For the existing population, it’s a matter of physician and patient awareness. "We need to educate physicians that this is an option," said Dr. Lanfear. "Awareness is lacking. There is a lot of heart failure out there that is underrecognized and underreferred. Neither patients nor their physicians realize how sick they are, and that they are at a high enough risk to justify this."