Author + information
- Received June 11, 2010
- Revision received January 6, 2011
- Accepted January 6, 2011
- Published online June 21, 2011.
- Robert M. Adamson, MD⁎ (, )
- Marcia Stahovich, RN,
- Suzanne Chillcott, BSN,
- Sam Baradarian, MD,
- Joseph Chammas, MD,
- Brian Jaski, MD,
- Peter Hoagland, MD and
- Walter Dembitsky, MD
- ↵⁎Reprint requests and correspondence:
Dr. Robert M. Adamson, Sharp Memorial Hospital, 7910 Frost Street, Suite 330, San Diego, California 92123
Objectives The primary objective of this study was to determine outcomes in left ventricular assist device (LVAD) patients older than age 70 years.
Background Food and Drug Administration approval of the HeartMate II (Thoratec Corporation, Pleasanton, California) LVAD for destination therapy has provided an attractive option for older patients with advanced heart failure.
Methods Fifty-five patients received the HeartMate II LVAD between October 5, 2005, and January 1, 2010, as part of either the bridge to transplantation or destination therapy trials at a community hospital. Patients were divided into 2 age groups: ≥70 years of age (n = 30) and <70 years of age (n = 25). Outcome measures including survival, length of hospital stay, adverse events, and quality of life were compared between the 2 groups.
Results Pre-operatively, all patients were in New York Heart Association functional class IV refractory to maximal medical therapy. Kaplan-Meier survival for patients ≥70 years of age (97% at 1 month, 75% at 1 year, and 70% at 2 years) was not statistically different from patients <70 years of age (96% 1 month, 72% at 1 year, and 65% at 2 years, p = 0.806). Average length of hospital stay for the ≥70-year age group was 24 ± 15 days, similar to that of the <70-year age group (23 ± 14 days, p = 0.805). There were no differences in the incidence of adverse events between the 2 groups. Quality of life and functional status improved significantly in both groups.
Conclusions The LVAD patients ≥70 years of age have good functional recovery, survival, and quality of life at 2 years. Advanced age should not be used as an independent contraindication when selecting a patient for LVAD therapy at experienced centers.
The utility and application of mechanical circulatory support (MCS) in patients with advanced heart failure has significantly progressed since the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial demonstrated superiority of the HeartMate I left ventricular assist device (LVAD) over optimal medical management (1). But these first-generation pulsatile devices were hindered by limited durability and high adverse event rates. A new era of MCS was ushered in by the development and subsequent Food and Drug Administration approval of the HeartMate II (HMII, Thoratec Corporation, Pleasanton, California) continuous-flow LVAD (2–5). With its excellent durability, improved patient survival, decreased incidence of adverse events, better patient satisfaction, and quality of life, it was shown to be a superior option to the HeartMate I for both bridge to transplant patients (2,3) and destination therapy patients (4). With an increasing population of elderly patients with advanced heart failure who have limited treatment options, there are unanswered questions pertaining to whether older patients can benefit from and are appropriate for this technology.
Congestive heart failure (CHF) is a common condition that increases with age. It is estimated that as many as 10% of people over the age of 70 years may be afflicted, and as many as 150,000 experience Class IV symptoms (6). Medical management of this population is expensive and offers limited survival and potential for functional recovery. Cardiac transplantation has traditionally been the gold standard for comparing end-stage heart failure management but with a small donor pool (approximately 2,000 per year in the United States), and the pragmatic restriction to patients under the age of 70 years, it appears that MCS will become the standard of care for older, refractory heart failure patients.
Patients with conditions such as advanced age, remote history of cancer, active infections, renal insufficiency, pulmonary artery hypertension, sensitization, and large body size especially with a common blood type could potentially be transplanted but their waiting times are typically prolonged. Older patients (age ≥70 years) are the largest potential group who could benefit from LVAD support, yet advanced age has consistently been identified as a risk factor for poor outcome (7–22). These studies have several limitations: 1) use of proven inferior technology (pulsatile devices); 2) registry data of LVADs in patients with diverse indications (i.e., failure to wean from cardiopulmonary bypass, deterioration while awaiting transplantation, and ongoing cardiogenic shock); and 3) data from a variety of mixed low-volume and high-volume centers. Therefore, extrapolation from these earlier results may not accurately reflect the expected outcome with the newer continuous-flow HMII device. Hence, the main objective of this study was to evaluate the outcomes of LVAD patients ≥70 years of age from a community hospital with an experienced LVAD team.
Patient inclusion criteria
All patients studied met the clinical trial enrollment criteria and the general criteria for bridge to transplantation/destination therapy LVAD implantation as published by the Centers for Medicare and Medicaid Services (23), including chronic end-stage heart failure (New York Heart Association [NYHA] functional class IV symptoms failing to respond to optimal medical management, end-stage left ventricular failure for at least 90 days, and a life expectancy of <2 years), left ventricular ejection fraction (LVEF) <25%, demonstrated functional limitation with peak volume of oxygen consumption (VO2) <12 ml/kg/min, continued need for intravenous inotropic therapy, and an appropriate body size to support LVAD implantation (23).
Through a National Coverage Determination issued on October 2003, Medicare began coverage of the destination therapy indication, and effective March 27, 2007, new facility criteria were established that require hospitals to receive certification from the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) (23). Facilities gaining JCAHO certification are placed on a list on the CMS website, which is continuously updated (23,24). During the current study, our facility achieved and maintained JCAHO certification as a Medicare-approved LVAD facility.
Pre-operative assessment and clinical optimization
The criteria adopted for selecting LVAD candidates are summarized in Table 1. All patients underwent comprehensive evaluation and treatment before LVAD placement that included clinical assessment of the severity of heart failure, hemodynamic state, cardiac anatomy, and operative risk. Inotropic support, diuresis or ultrafiltration, infection surveillance/treatment, and nutritional assistance were provided when needed. On the basis of response to treatment, it was determined whether the patient should continue medical treatment or hospice, high-risk surgical repair with LVAD standby, or become a candidate for destination LVAD therapy or transplantation. For nonresponders, the decision was whether they were appropriate LVAD candidates or too sick for support. Noncardiac considerations such as history of chronic or life-limiting illnesses, mental status, nutritional status, expectations (quality of life versus duration of life), and psychosocial and age-related considerations were assessed.
A neurological evaluation was ordered if necessary to rule out degenerative central nervous system diseases and dementia. Because it is imperative that candidates for LVAD therapy demonstrate the ability to operate the device safely, we assessed for stroke, psychiatric disorders, mental retardation, substance abuse, and other factors that could potentially impact compliance with medical regimen and clinic visit follow-ups (25).
Patient's baseline renal function was reviewed because poor baseline renal function is associated with worse outcomes after LVAD implantation (26–28). This review included assessment of renal parameters as well as pre-operative diuretics use and aggressive treatment of heart failure (inotropic support, ultrafiltration, or dialysis).
For each patient, a comprehensive assessment was made to define the degree of malnutrition and estimate the severity of illness. We typically use the Subjective Global Assessment and Severity of Illness scales to determine the level of malnutrition and to determine when to start nutritional support (29).
When evaluating the patient's social support network, we reviewed the presence and age of the caregiver, such as a spouse or family member, who could be available in case of device malfunction. We reviewed a plan of care for discharge that would ensure that the home environment was safe and allow the patient to receive adequate post-operative care. We looked at patients' ability to care for themselves, including eyesight, hearing, dexterity, and evidence of poor dentition, as well as any history of noncompliance with medical regimens. Social workers reviewed the availability of patient-related community resources. If significant questions were unanswered, then a trained home health nurse visited the patient's home to complete the assessment.
All patients received the information necessary to assist them in giving appropriate informed consent for the procedure. The patient and significant others signed a healthcare contract delineating the expectations for after care.
Prevention of right-side heart failure was implemented in all patients, and included the routine use of inhaled nitric oxide, biventricular pacing when necessary, and the use of inotropic drugs such as isoproterenol, dopamine, and milrinone in the immediate post-operative period. Patients with impaired right ventricular function were given sildenafil routinely, and the inhaled nitric oxide was weaned within 24 to 48 h in most cases. Nursing care in the cardiac step-down unit focused on strengthening, self-care, and education about LVAD management.
Fifty-five consecutive patients receiving HMII LVADs included in the bridge to transplantation or destination therapy clinical trials from October 2005 to January 2010 at a small community hospital with extensive MCS experience were evaluated. Patients were divided into 2 groups on the basis of age at the time of implant: patients <70 years of age (n = 25), and patients ≥70 years of age (n = 30). During the study period, 329 patients were referred for consideration of LVAD or transplantation, and of those, 15% (49 of 329) were age 70 years or older. The majority, 61% (30 of 49), of patients 70 years of age or older accepted and underwent HMII implant. Four patients (8%) were considered to be good candidates but refused our recommendation, 16% (8 of 49) were too well, whereas only 8% (4 of 49) were too ill. One patient underwent traditional heart surgery (coronary artery bypass graft) and mitral valve repair, 1 patient had insufficient psychosocial support, and 1 patient was lost to follow-up and the precise reason for refusal was unknown. In the younger than 70 years of age population, 46% (103 of 280) either received a HMII or underwent transplant, 14% (40 of 280) were too well, 5% (13 of 280) underwent a traditional cardiac operation, 4% (10 of 280) were too ill, 13% (37 of 280) were not considered to be good LVAD candidates, 8% (24 of 280) failed to keep their appointment, and 3% (9 of 280) refused to accept our advice for LVAD or transplant. Only patients implanted as part of the HMII trial were studied, as complete datasets were available only for these patients.
The groups were compared with regard to pre-operative patient characteristics and outcome measures, including Kaplan-Meier survival, prevalence and incidence of adverse events, quality of life metrics (Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores and Overall Summary Scores, Minnesota Living With Heart Failure questionnaire), and functional status (6-min walk distance, NYHA functional class, and patient activity levels with the Metabolic Equivalent Task Score) (5).
Statistical analyses except for Poisson regression were done using SYSTAT (Cranes Software, Chicago, Illinois). Poisson regression was performed using SAS (SAS Institute, Cary, North Carolina). Differences between groups of independent, normally distributed, continuous variables were evaluated using the t test. Variables that were not normally distributed were evaluated using the Mann-Whitney U test. Normality was checked using the Anderson-Darling test. Differences in categorical variables were evaluated using the Fisher exact test. Statistical comparisons were 2-sided, and the level of significance was set at p < 0.05. Survival analysis was performed using the Kaplan-Meier method, with patients censored for transplantation, recovery of native heart function with device removal, or withdrawal from the study. Comparison of survival between the 2 groups was performed using the log-rank test. Adverse events are presented as both percentages of patients and event rates (events per patient-year). Comparisons of adverse event rates between the 2 groups were performed using a Poisson regression model (Mantel-Haenszel), with the total duration of support as the exposure time and total number of events as the response variable. Quality of life comparisons were performed using linear mixed-effects modeling (MIXED subroutine in SYSTAT). The predictor variables were age group, time group (baseline, 1 month, 3 months, and 6 months), and age group by time group. Eight patients (4 in each group) had a previous pulsatile flow LVAD that was replaced with an HMII LVAD. Duration of support and survival for these patients was evaluated from the date of the first LVAD implant. Only adverse events that were observed when on the HMII device were included.
Baseline patient characteristics
The age distribution of LVAD patients in this study shows most were between the ages of 60 and 80 years (Fig. 1) Baseline characteristics were similar between groups except for age, nutritional status (pre-albumin), use of angiotensin-converting enzyme inhibitors, and ventilator support (Table 2). There was a tendency for a higher prevalence of ischemic etiologies and prior cardiac resynchronization therapy in the ≥70-year age group than in the <70-year age group, but these differences were not statistically significant. All patients were in NYHA functional class IV before LVAD implant. There was no difference in the mean Lietz-Miller destination therapy risk score (30) between the <70-year age group (10.5 ± 6.3) and ≥70-year age group (8.3 ± 5.8, p = 0.205), nor in the percentage of patients with high/very high risk scores or low risk scores.
Associated concomitant operative procedures are listed in Table 3. Four patients in each group had a prior HeartMate XVE exchanged for an HMII. There were no statistically significant differences between the 2 groups in the number of patients undergoing mitral valve repair/replacement, tricuspid valve repair/replacement, aortic valve patch closure, patent foramen ovale closure, or any other concomitant procedures performed at the time of surgery. One ≥70-year-old patient had a right ventricular assist device (Biomedicus pump, Medtronic, Minneapolis, Minnesota), which was removed after 2 days, compared with none in the <70-year age group. Cardiopulmonary bypass times were similar between the <70-year age group and ≥70-year age group (80 ± 32 min vs. 83 ± 41 min, p = 0.760).
Duration of support
Patients in the <70-year age group were supported for an average of 678 ± 676 days (median 415 days, range 8 days to 8 years), and patients in the ≥70-year age group were supported for 539 ± 475 days (median 482 days, range 19 days to 5.6 years; p = 0.630). Thirteen patients in the <70-year age group were supported with an LVAD for >1 year, including 9 patients for >2 years, 4 patients for >3 years, 3 patients for >4 years, and the longest, for 8 years. Comparatively, 16 patients in the ≥70-year age group were supported for >1 year, including 8 patients for >2 years, 4 patients for >3 years, 2 patients for >4 years, and the longest, for 5.6 years.
The Kaplan-Meier survival for both groups were comparable (log-rank p = 0.806) (Fig. 2A). Survival rates for the <70-year age group versus ≥70-year age group were similar at 30 days (96% vs. 97%), 6 months (88% vs. 83%), 1 year (72% vs. 75%), and 2 years (65% vs. 70%). Survival rates for patients receiving the HMII as their initial device, after excluding those who received it as an exchange for the XVE, were also similar (p = 0.898) at 1 year (65% vs. 70%) and 2 years (65% vs. 70%) (Fig. 2B). In the <70-year age group, 6 patients (24%) died, 2 patients (8%) were transplanted, 1 patient (4%) recovered cardiac function and had the LVAD removed, and 16 patients (64%) were still receiving ongoing LVAD support (3 for <1 year, 13 for >1 year) at 1 year. Similarly, in the ≥70-year age group, 7 patients (23%) died, none underwent transplant or recovered cardiac function, and 23 (77%) were still receiving ongoing LVAD support (7 for <1 year, 16 for >1 year) at 1 year. No significant differences in the causes of death were observed between the 2 groups (Table 4).
Length of stay and hospital course
The average length of stay in the hospital was similar for the <70- and ≥70-year age groups (23 ± 14 days vs. 24 ± 15 days, respectively; p = 0.805). Some patients stayed longer in the intensive care unit, primarily for respiratory care and right ventricular weaning of intravenous inotropic medications. Non–device-related rehospitalizations included infirmaries related to orthopedic surgery, cholesystectomy, transurethral resection of the prostate, and Clostridium difficile infection.
Quality of life and functional status
Outcomes associated with the quality of life and functional status are shown in Table 5. The percentage of patients in NYHA functional class I or II improved from 0% at baseline to 100% (<70-year age group) and 89% (≥70-year age group) at 6 months. There were statistically significant improvements in the 6-min walk distance from baseline (for those able to walk) to 6 months for the <70-year age group (256 to 275 m) and the ≥70-year age group (233 to 295 m). There were also significant improvements by approximately 36 (<70-year age group) and 42 points (≥70-year age group) at 6 months in heart failure-related quality of life metrics using the Minnesota Living With Heart Failure Questionnaire. Similarly, there was a 32-point increase (<70-year age group) and a 42-point increase (≥70-year age group) in mean values of the Kansas City Cardiomyopathy Questionnaire overall summary score (Table 5). Patient activity levels significantly increased in this period as well. The percent of patients achieving a Metabolic Equivalent Task Score of 3 (moderate activity) or higher improved from 12% at baseline to 63% at 6 months (<70-year age group) compared with 7% to 52% (≥70-year age group). Overall, there was no difference in any of the quality of life or functional status metrics between the 2 groups.
The incidence of adverse events (Table 6) was similar between the <70-year and ≥70-year age groups for bleeding requiring packed red blood cells (0.33 vs. 42 events per patient-year, p = 0.591) and requiring surgery (0.15 vs. 0.11, p = 0.583), device-related infection (0.15 vs. 0.13 events per patient-year, p = 0.813), and incidence of hemorrhagic stroke (0.03 vs. 0.05 events per patient-year, p = 0.557) and ischemic stroke (0.03 vs. 0.03 events per patient-year, p = 0.985).
This study shows that excellent results can be obtained with LVAD support as destination therapy for advanced heart failure patients over the age of 70 years. We believe that this type of mechanical support should be considered as an attractive option for select patients refractory to maximal medical therapy, and that age should not be an absolute contraindication to LVAD support. The results also indicate that very good results can be achieved in a community hospital setting with a focused effort from a dedicated team.
Even though heart failure is a major public health problem affecting >5 million Americans, with an estimated 250,000 in NYHA functional class IV heart failure, and early LVAD technology was proven superior to medical therapy, there was only a modest increase in the number of patients receiving LVADs. Lietz et al. (15) reported that only 451 patients underwent destination therapy device placement with pulsatile LVADs during the first 5 years after the REMATCH trial, and destination therapy accounted for only 17% of the devices implanted. Also, with the incidence of NYHA functional class IV heart failure increasing with age, one would expect national LVAD volumes to dramatically increase among elderly patients, but that has not been the case.
The main reason for this discrepancy is that the pulsatile devices had poor reliability and significant adverse events rates. Although there was a survival advantage demonstrated in the REMATCH study, the outcomes led many to question whether the increased length of life was worth the expense to both the patients and the health care system. Another factor is age, which has consistently been identified in multiple studies as a risk factor for decreased survival and increased adverse events after LVAD placement (7–22). However, these previous studies have significant limitations. First, the impact of comorbidities and the presence of irreversible cardiogenic shock were not controlled. Second, many studies used a mixture of devices in their review that may confound the overall analysis, and some of the data come from registries for which the robustness of the data is suspect. Given these shortcomings, we do not have sufficient published data on continuous-flow devices implanted at experienced centers to conclude that advanced age should be a contraindication to LVAD therapy.
One important positive factor in the use of LVAD therapy for older patients is that they are very appreciative of the improved quality of life afforded by the LVAD. Whereas younger patients want to live longer, older patients want to live better. Older patients are also typically more compliant with medications and instructions from caregivers, and do not have increased adverse events just because of their age. Selecting the right older patient is critical. Older patients can have more associated illnesses and other concomitant problems with the native heart that need to be considered. Rigorous assessment and optimization of pre-operative status should be undertaken, including neurological, nutritional, psychosocial, and renal assessments. Optimal outcomes in LVAD patients can be achieved with a dedicated LVAD team organized and charged with implantation, early post-operative management, and outpatient management, as outlined in a recent publication on clinical management of continuous flow LVADs (31). Our study shows that if such practices are adopted, then good outcomes can be achieved.
Center experience has been shown to play an important role in determining outcomes with LVAD therapy (15). Our implant techniques, patient selection, and management protocols are constantly improving. This study demonstrates that destination therapy LVAD therapy can safely be delivered to an older patient population in a small community hospital with an experienced team. In fact, our survival rates are higher and the rates of adverse events were lower in both groups when compared with the results of the multicenter HMII trials (2–4). Similar outcomes can be achieved in other hospital settings as well.
Patient selection is an important question to be answered if these results are to be duplicated in other centers. The majority of referred patients age 70 years or older (61%) were considered to be good candidates and successfully received their LVADs. From epidemiologic data, we know that the number of elderly patients with terminal heart failure is much larger, so one must assume that only a very small and select sample of this population is being referred. We have no way to evaluate why physicians do not refer some patients, but we can say that on 3 occasions patients were self-referred from hospice and successfully implanted, implying that many patients who are acceptable candidates are not referred.
The main limitation of this study is that observations were based on small numbers of patients from a single center participating in a multicenter clinical trial. The review of patients referred for terminal heart failure evaluation was retrospective, and therefore the numbers are less reliable for total patients referred and identifying the precise reasons for refusal.
Advanced heart failure patients receiving an HMII LVAD who were older than 70 years had outcomes similar to those of patients younger than 70 years. Older patients had acceptable length of hospital stays, adverse events, and functional recovery. Advanced age should not be used as an independent contraindication when selecting a patient for LVAD therapy. As this technology continues to improve, increasing numbers of older patients will seek centers for destination therapy. Analysis of the referral data suggests that more patients should be referred for LVAD evaluation at an experienced center, because good outcomes can be achieved in this patient cohort.
All authors are on the Speakers' Bureau for Thoratec Corporation. Sharon A. Hunt, MD, served as Guest Editor for this paper.
- Abbreviations and Acronyms
- congestive heart failure
- Destination Therapy Risk Score
- Joint Commission on Accreditation of Healthcare Organizations
- left ventricular assist device
- left ventricular ejection fraction
- mechanical circulatory support
- New York Heart Association
- Received June 11, 2010.
- Revision received January 6, 2011.
- Accepted January 6, 2011.
- American College of Cardiology Foundation
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