3B or Not 3B? Should Patients Get an LVAD Before Reaching End-Stage HF?

Reed Miller

January 30, 2012

January 30, 2012 (Ft Lauderdale, Florida) — Surgeons and ventricular-device developers want to use mechanical circulatory support to prevent moderate heart failure from progressing to severe end-stage heart failure (NYHA class 4), but identifying non–end-stage patients who will benefit from mechanical circulatory support remains difficult.

In a staged debate here at the Society of Thoracic Surgeons (STS) 2012 Annual Meeting, Dr Valluvan Jeevanandam (University of Chicago, IL) and Dr Francis Pagani (University of Michigan, Ann Arbor) debated the merits of implanting left-ventricular assist devices (LVADs) in class 3B patients.

Dr Valluvan Jeevanandam Source: University of Chicago

"If you ask [whether] these devices are ready for implant into less sick patients, the answer is that we certainly have devices that are very durable and have good long-term results," Jeevanandam said in his presentation of the "pro" position.

In the REMATCH trial completed about a decade ago, the first HeartMate (Thoratec) pulsatile LVAD improved two-year survival of transplant-ineligible NYHA class 4 patients from 25% to 52%, compared with medical therapy alone. At the time, that modest survival benefit marked a major breakthrough in mechanical circulatory support, but the latest data on the continuous-flow HeartMate II shows 85% of patients supported by the device survive at least one year, and HeartWare is boasting a near 90% one-year survival with its VAD, he said.

"There's been a clear progression and, at this point, the devices are ready, but do we have the data [to support expanding LVADs' indication]?" Jeevanandam asked. "The market has already answered that, because the devices are already going into less sick patients," he said. The INTERMACS registry shows that the number of LVAD recipients with INTERMACS score 1 [the sickest patients] dropped from 35% to 17% from 2009 to 2010.

Also, one- and two-year survival rates of patients classified as NYHA 3B in the HeartMate II destination-therapy trial were 78% and 68%, respectively, comparing favorably with the survival rates of class 3B patients treated with medical therapy alone, he said.

Can 3B Even Be Defined?

However, Jeevanandam conceded that "one of the most difficult things is to define a class 3b patient." Jeevanandam and Pagani both pointed out that the patients called class 3B in the HeartMate II trial may not have been "true" 3B patients, because 10% were on balloon pumps and 68% were on inotropes, almost the same proportion of patients on inotropes in the NYHA class 4 population enrolled in the original REMATCH trial, Pagani said.

Dr Francis Pagani Source: University of Michigan

"This is not a 3B population of patients, yet we're justifying an inappropriate labeling of this class of patients to justify use of an LVAD in a less ill population of patients," he said. He calculated that the difference between the two-year survival of patients classified as NYHA 4 vs those classified as 3B is 4% and not statistically significant.

Pagani argued, "The debate [should not be] whether we should be doing VADs in less ill patients, but [determining] the correct way to identify these less ill patients and [whether] NYHA 3B is the correct way of [identifying them]."

He explained that the there has never been any formal recognition of NYHA class 3B and that the difference between class 3B heart failure and class 4 heart failure is "highly subjective" and based only on symptom assessment. "The New York Heart Association is a very poor way to identify prognosis for patients with heart failure," he said.

Finally, a Randomized Trial

"We have not rigorously evaluated LVAD therapy in the population of patients who are ambulatory and not inotrope dependent," Pagani said. "The real question is, what is the marginal benefit of LVAD therapy on less ill patients? And if survival is not improved in the less ill cohort of patients, what are the trade-offs with respect to functional outcomes and quality of life compared with the adverse-events profile of stroke, infection, and bleeding?" he asked "These questions are best asked in a randomized controlled trial."

Pagani is one of the principal investigators of the REVIVE-IT trial, which will randomize about 100 ambulatory, non–inotrope-dependent patients with NYHA class 3 heart failure to either the HeartWare VAD or optimal medical therapy. The primary end point will be a composite of survival, freedom from moderately disabling stroke, and improvement of six-minute-walk distance.

Jeevanandam serves as a consultant for Thoratec, HeartWare, and Vascutek, a Terumo company. Pagani has received research grants from HeartWare and the National Heart, Lung, and Blood Institute.