Long-term mechanical circulatory support (destination therapy): on track to compete with heart transplantation?

Abstract

Objectives: Average 2-year survival after cardiac transplantation is approximately 80%. The evolution and subsequent approval of larger pulsatile and, more recently, continuous flow mechanical circulatory support (MCS) technology for destination therapy (DT) offers the potential for triage of some patients awaiting cardiac transplantation to DT.

Methods: The National Heart, Lung, and Blood Institute Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a national multi-institutional study of long-term MCS. Between June 2006 and December 2011, 127 pulsatile and 1160 continuous flow pumps (24% of total primary left ventricular assist devices [LVADs]) carried an initial strategy of DT therapy.

Results: By multivariable analysis, risk factors (P < .05) for mortality after DT included older age, larger body mass index, history of cancer, history of cardiac surgery, INTERMACS level I (cardiogenic shock), dialysis, increased blood urea nitrogen, use of a pulsatile flow device, and use of a right ventricular assist device (RVAD). Among patients with a continuous flow LVAD who were not in cardiogenic shock, a particularly favorable survival was associated with no cancer, patients not in cardiogenic shock, and blood urea nitrogen less than 50 mg/dL, resulting in 1- and 2-year survivals of 88% and 80%.

Conclusions: (1) Evolution from pulsatile to continuous flow technology has dramatically improved 1- and 2-year survivals; (2) DT is not appropriate for patients with rapid hemodynamic deterioration or severe right ventricular failure; (3) important subsets of patients with continuous flow DT now enjoy survival that is competitive with heart transplantation out to about 2 years.

Figure 1

Categorization of all 5,614 patients entered into INTERMACS between June 23, 2006 and December 31, 2011. The group Destination Therapy (n=1,287) constitutes the study group.

Figure 2

Primary device implant by year, stratified by device type, for the entire INTERMACS experience. LVAD, left ventricular assist device; RVAD, right ventricular assist device; TAH, total artificial heart; Cont, continuous flow; Intra, intracorporeal; Puls pulsatile; Para, paracorporeal.

Figure 3

Destination Therapy device implants by year, stratified by device type.

Figure 4

Competing outcomes depiction for pulsatile flow left ventricular assist devices (LVAD) implanted with a strategy of destination therapy. All outcome events are mutually exclusive, such that the some of all probabilities at any point in time equals 100%. *Includes LVAD only as well as LVAD plus an RVAD implanted for RV failure at original LVAD implant or anytime thereafter.

Figure 5

Competing Outcomes Depiction for continuous flow left ventricular assist devices implanted with a strategy of Destination Therapy. The depiction is as in Figure 4.

Figure 6

Actuarial freedom from device exchange or death secondary to device malfunction or device complication, stratified by device type. The lower curves represent the hazard function for this event for each device type. The dashed lines enclose the 70% confidence limits. *See notation in Figure 4.

Figure 7

Actuarial survival among 1,287 patients receiving destination therapy LVAD support. Patients are censored at time of transplant or explant due to recovery. The lower curve represents the hazard function. The dashed lines enclose the 70% confidence limits. *See notation in Figure 4.

Figure 8

Actuarial survival following Destination Therapy LVAD, stratified by age at implant. Patients are censored at transplant or explant for recovery. LVAD, left ventricular assist device; BIVAD, biventricular assist device. *See notation in Figure 4.

Figure 9

Actuarial survival following Destination Therapy LVAD, stratified by INTERMACS level at time of implant. The INTERMACS levels are defined in Appendix 3. LVAD, left ventricular assist device; BIVAD, biventricular assist device. *See notation in Figure 4.

Figure 10

Actuarial survival following Destination Therapy LVAD, stratified by device location and pump type. Patients are censored at transplant or device explant for recovery. LVAD, left ventricular assist device; CFP, continuous flow pump PFP; pulsatile flow pump; BiVAD, biventricular assist device (implanted at time of LVAD implant).

Figure 11

Bar chart indicating the timing of RVAD implant. LVAD, left ventricular assist device; RVAD, right ventricular assist device.

Figure 12

Actuarial survival among Destination Therapy patients, stratified by device type. Patients are censored at time of transplant or explant due to recovery. LVAD, left ventricular assist device; BIVAD, biventricular assist device. *See notation in Figure 4.

Figure 13

Percent of patients with some and extreme problems with self care before and at intervals after Destination Therapy with a continuous flow (CF) left ventricular assist device (LVAD). See Materials and Methods for definition of EQ5D. RVAD, right ventricular assist device.

Figure 14

Percent of patients with some or extreme problems with usual activities before and at intervals after Destination Therapy with a continuous flow pump. The depiction and abbreviations are as in Figure 14.

Figure 15

EQ5D visual analog scale (see Materials and Methods for definition) before and at intervals after Destination Therapy with a continuous flow pump. The abbreviations are as in Figure 13.

Figure 16

Survival after cardiac transplantation, stratified by era. Reproduced with permission, International Society for Heart and Lung Transplantation Registry.

Figure 17

Solutions to the multivariable equation (see Appendix 5). The nomograms are generated with variables set as indicated for 2 patients according to age at implant. The dashed lines indicate the 70% confidence limits around the solution curve. BMI, body mass index; Bi-VAD, biventricular support; BUN, blood urea nitrogen.

Figure 18

Solutions to the multivariable equation (see Appendix 5). The nomograms are generated with variables set as indicated for 2 patients according to Body Mass Index. Depiction is as in Figure 17.

Figure 19

Actuarial survival stratified by high, medium, and low risk patients. “Risk factors” include presence of biventricular support (BiVAD), previous cancer, body mass index (BMI) greater than 32, serum sodium less than 130, or blood urea nitrogen (BUN) greater than 50.