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Adult Circulatory Support

Impact of Patient Distance From Ventricular Assist Device–Implanting Center on Short- and Long-Term Outcomes

Ravichandran, Ashwin K.*; Shah, Palak; Singh, Ramesh; Aaronson, Keith D.; Pagani, Francis D.; Stulak, John§; Dunlay, Shannon M.§; Dardas, Todd F.; Mokadam, Nahush A.; Salerno, Christopher T.*; Cowger, Jennifer A.*

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doi: 10.1097/MAT.0000000000000717
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Abstract

The advent of continuous flow left ventricular assist device (LVAD) technology has greatly increased the survival of patients with end-stage heart failure. With an insufficient number of cardiac transplant donors and improved LVAD short- and long-term survival, the number of patients living on LVAD support has steadily increased.1 Consequentially, an ambulatory population of LVAD patients are reintegrating into a diverse range of urban, rural, and suburban communities, bringing with them the medical complexities of assessing hemodynamic status on nonpulsatile flow and the consequences of device-related complications, including ischemic and hemorrhagic strokes, pump thrombosis, gastrointestinal (GI) bleeding, infection, as well as the need for interpreting device alarms and the maintenance of batteries, power modules, and drivelines.

In many countries including the United States, Canada, and the United Kingdom, the highly specialized care that LVAD patients require is often concentrated near urban areas, potentially limiting access to health care for patients living in rural areas. Conflicting data exist in the medical literature regarding the impact of distance traveled to receive medical care on patient outcomes.2–6 In a recent comprehensive review of several studies (n = 177) primarily looking at oncologic and primary care, 77% of studies demonstrated that close proximity to a variety of primary and secondary medical care services conferred a positive impact on patient outcomes, likely because of a higher utilization of health care services.3 This reduction in patient survival with greater distance from specialized care has been termed the “distance decay association.”2,3,5 Conversely, 18% of studies showed neutral outcomes, whereas 6% demonstrated improved patient survival in those who lived farther from a medical center.3 This latter observation is termed the “distance bias association” and is theorized to be a result of referral bias.2,3,5

Most studies examining outcomes based on patient distance focused on elective procedures or the detection and treatment of cancer. Left ventricular assist device patient care (in both the inpatient and outpatient setting) is resource intensive and enduring. As such, extrapolation of results from other disease processes could be erroneous. Using a multicenter research network of high-volume LVAD centers, this analysis examines the relationship of short- and long-term outcomes stratified by patient distance from the implanting center.

Methods

A retrospective analysis of data collected on patients (n = 1184 from 2007 to 2016) undergoing Food and Drug Administration–approved continuous flow LVAD implant as part of the Mechanical Circulatory Support Research Network (MCSRN) was performed. Centers contributing data to this MCSRN analysis included St. Vincent Heart Center of Indiana (n = 351), Mayo Clinic (n = 316), Inova Heart and Vascular (n = 166), and the University of Michigan (n = 351). Distance from the LVAD implant center was calculated from patient zip codes provided at the time of admission using the website https://www.zip-codes.com/distance_calculator.asp, which calculates driving distance. Patients were initially grouped into 30 mile distance increments from the medical center. The 90 mile threshold was chosen, representing approximately the top distance tertile (98 miles).

The primary outcome of interest was long-term survival (defined as survival at 3 years) based on patient distance from LVAD implant center. Secondary outcomes included 90 day survival (chosen based on highest hazard of early mortality1) and incident event rates for the following: GI bleeding (defined as heme-positive stool with acute drop in hemoglobin >2 g), infection requiring intravenous antibiotics (pneumonia, endocarditis, driveline infection, pump infection, sepsis), cerebral event (ischemic or hemorrhagic stroke or transient ischemic attack leading to admission), hemolysis (>2.5 times the lactate dehydrogenase (LDH) upper limit of normal requiring admission because of clinical concerns), or device exchange.

Patient Follow-Up

Each MSCRN institution has its own patient follow-up protocol:

  1. St Vincent: follow-up at weeks 1 and 5 after discharge, and every 2–3 months thereafter. Shared care is individualized to the patient’s needs.
  2. University of Michigan: follow-up biweekly for the first 3 months, monthly to the end of year 1, and every 2–3 months thereafter. Shared care is individualized to the patient’s needs.
  3. Inova Heart and Vascular Institute: follow-up weekly for 1 month, bi-weekly for 2 months, monthly to 6 months, and then every 3 months thereafter. Shared care is individualized to the patient’s needs.
  4. Mayo protocol: follow-up monthly for the first 3 months, then every 3 months until 1 year, then every 4 months until year 2, and every 6 months thereafter.

Statistical Analysis

Continuous variables were evaluated for normality and are presented as mean ± standard error or median (25th, 75th), as appropriate. Continuous data were compared with parametric (Student’s t testing) or nonparametric (Mann–Whitney U test) tests. Categorical data were compared with Fisher’s exact testing or Pearson’s χ2 test for >2 × 2 comparisons.

Survival estimates were obtained using the Kaplan–Meier method. Patients were censored at the time of transplant, transfer of care to another center, or device explant for recovery. Standard log-rank p values were used when comparing survival at the 90 mile threshold, and Cox regression was used to generate hazard ratios (HR; 95% confidence interval) for survival. Log-rank p values for linear trend were used to compare survival across multiple zip code groupings. The log-rank linear trend tests the null hypothesis that there is no linear trend between the ordered patient distance groupings and median survival. An adjusted HR for mortality was calculated controlling for known clinical correlates for ventricular assist device (VAD) mortality (age, destination therapy [DT] indication at time of implant, preoperative creatinine, albumin and prior sternotomy,1,7 as well as implant center and patient distance. Incident events were calculated for secondary end points. For all analyses, a p value ≤0.05 was considered statistically significant.

At all centers, internal review board approval was obtained for MCSRN data collection and analysis.

Results

There were 1184 patients supported for a median 486 (202, 937) days. Table 1 shows the baseline characteristics and demographics of the MCSRN cohort. Overall survival was 91 ± 0.8% at 90 days and 61 ± 1.9% at 3 years. Median distance from implant center across the four institutions was 62 (28, 136) miles and a mean of 122 miles. Figure 1 shows the percentage of patients in each of seven distance categories. Over 50% of patients lived within 60 miles of the VAD implant center.

Table 1.
Table 1.:
Baseline Characteristics and Demographics of the Total MCSRN Cohort and by Distance From VAD Implant Center
Figure 1.
Figure 1.:
Numbers of patients in each distance sector by 30 mile increments. VAD, ventricular assist device.

Average survival according to the distance between a patient’s home and the VAD implant center is shown in Figure 2. As distance increased, patient survival decreased (log rank for linear trend p = 0.018). Compared with patients living within 30 miles of their VAD implant center, survival was inferior at distances of 91–120 miles (HR = 1.4; [1.1–1.9]) and distances more than 180 miles (HR = 1.4; [1.0, 2.1]; Figure 2) on pairwise comparisons. There was no difference in survival between patients living 0–30, 31–60, or 61–90 miles from a VAD implant center (p > 0.05 for all comparisons).

Figure 2.
Figure 2.:
Survival according to distance between patient’s home and ventricular assist device (VAD) implant center. Survival was worse in patients living farther from the VAD implant center.

Outcomes by 90 Miles Distance Thresholds

There were 746 (63%) patients who lived within 90 miles of the VAD implant center and 438 (37%) beyond 90 miles. Groups were similar with regard to sex, INTERagency for Mechanically Assisted Circulatory Support (INTERMACS) profile, vasopressor use, and cardiomyopathy etiology (Table 1). Patients living >90 miles from an implant center were older, more likely to be implanted for DT support, had required a prior sternotomy, and had worse renal function than those living closer (p < 0.05 for all).

Of the 325 deaths during the 3 years of follow-up, 149 occurred early (within 90 days). Of the early deaths, 41% occurred in those living ≤90 miles from an LVAD center and 36% occurred in those living >90 miles away (p = 0.32). There was no difference in survival to hospital discharge either (p = 0.2). At 3 years, survival was worse in patients living >90 vs. ≤90 miles from the VAD implant center (55 ± 3.0% vs. 64 ± 2.5%, p = 0.019; Figure 3). Survival curves appeared to separate later (>1 year) after implant. The unadjusted HR for patients living more than 90 miles from the LVAD hospital was 1.25 (1.03–1.53; p = 0.023). After adjusting for center of implant, age, DT indication, creatinine, albumin, and prior sternotomy, the mortality HR for living >90 miles from a VAD implant center was of similar magnitude but not of statistical significance (adjusted HR = 1.2 [0.95, 1.4]; p = 0.14). Table 2 shows the causes of death by distance grouping. Patients who lived >90 miles away had more unknown causes of death, and more deaths from strokes, ventricular arrhythmias, multisystem organ failure, and right ventricular failure than those patients who lived closer (p = 0.003 for overall cause of death comparison by distance).

Table 2.
Table 2.:
Causes of Death Based on Distanced From VAD Implant Center
Figure 3.
Figure 3.:
Survival in patients living within and outside 90 miles of the ventricular assist device (VAD) implant center.

At 3 years, patients living within 90 miles of the implant center were more likely to be transplanted (41 ± 2.5%) than patients living farther away (32 ± 2.9%, log-rank p = 0.018). Restricting the analysis to those who were considered bridge-to-transplant (BTT) at implant, there was no difference in the frequency of transplant by distance (35 ± 3.4% vs. 32 ± 4.9%, p = 0.71). Except for GI bleeds, events were more common in patients living closer to the implanting center (Table 3).

Table 3.
Table 3.:
Incidence and Rates of Events Based on Distance From VAD Implant Center

Discussion

In this multicenter study, patients who lived farther away from their LVAD implanting center had worse unadjusted survival, with a clear dichotomization of outcomes for those living greater than 90 miles away. Ninety day survival was similar across patient distances, suggesting that the reductions noted in survival were driven by events occurring after the operative period. Except for GI bleeding, the event rates and frequency of secondary outcomes were greater for those living closer to the implanting center. Additionally, patients traveling longer distances were less likely to be transplanted, a finding that can be attributed to older patient age and a higher frequency of DT device intent. After controlling for covariates of LVAD mortality, patient distance did not reach statistical significance (p = 0.14) as a correlate of death. However, the direction and magnitude of the HR (1.2) were similar to unadjusted values. It cannot be determined from the data herein if power limited statistical significance. However, the absence of significant differences in operative mortality (the period of highest mortality hazard) makes trends for inferior outcomes with increasing patient distance worth noting.

The trend toward improvements in survival gained by living closer to the LVAD implant center could be consistent with the concept of “distance decay,” such that LVAD patients living nearer to the implanting center enjoy greater access to healthcare resources and LVAD specialty care.3 In addition, patients living further from the LVAD center also had a greater burden of risk factors for post-LVAD mortality, including older age, prior sternotomy, and preoperative renal dysfunction. Of these risk factors, however, only age has been shown to be a predictor of long-term survival.7 Preoperative creatinine and prior sternotomy, thus far, have only been shown to be predictive of early LVAD mortality and do not forecast survival in analyses restricted to patients who have survived the operative period.7 In the present analysis, early survival (90 days) was similar across patient distances, and the survival curves did not begin to separate until >1 year after LVAD implant, implying that factors other than operative risk/mortality are potential drivers for the tendency toward worse outcomes in those living further from their implant center.

In contrast to these survival trends, a paradoxical increased frequency of adverse events (except GI bleeding) was found in those living closer to the implant center. There are several potential explanations for these findings. Distant patients may have received care at local, non-LVAD facilities. In this scenario, enumeration of events could be falsely low if complications were unrecognized or not made aware to the implanting center. However, this seems less likely since patients were censored upon last follow-up, and all other patients had time on support ended at the last patient encounter (phone or clinic). Alternatively, patients who lived closer to their LVAD center may have had improved identification of adverse events compared with those living further away. In some medical conditions, this finding can result from diagnosis bias, in which a physician’s diagnostic approach is more aggressive because of knowledge about disease-specific complications, leading to increased recognition of complications early in the disease course. With diagnosis bias, however, outcomes are not improved because of detection of insignificant disease.8 In the current study, patients living closer to the LVAD center had more complications but also had an inclination toward greater survival than those living >90 miles out. As such, it is more likely that patients living further away from an implant center may have had delayed care with associated increased mortality from unaddressed complications. This hypothesis is supported by the increased death from unknown causes and multisystem organ failure. This study was not designed to answer whether and why patients living farther from an LVAD center were less likely to seek timely medical care.

If these findings are supported by other independent analyses, the clinical implications are important for patients with advanced heart failure living remotely from LVAD centers. Certainly, improved outcomes may be seen if patients are implanted at an LVAD center that is closer to their homes. In this analysis, long patient distances may partially be explained by aberrant referral patterns. For some patients, payor rules mandated in-state device implant even if a closer VAD implant center existed across state lines. Additionally, insurance policies, Medicaid expansion, and the advent of health exchanges vary across state lines and are not accounted for in this analysis.

Although improving access to LVAD specialty care within the United States and abroad may lead to improved patient outcomes, this is undoubtedly no small endeavor. Recent evidence has shown that low center surgical LVAD volumes (<10 devices a year) are associated with increased short- and long-term mortality after LVAD implant.7,9,10 Further, the intricate, multidisciplinary care required of LVAD inpatients encompass not only cardiology but also other disciplines such as gastroenterology, infectious diseases, and hematology who are familiar with LVAD physiology and complications.11 Unlike procedures such as complex valve interventions and transcatheter aortic valve replacements, where outpatient follow-up care after the operative intervention is short, follow-up of the LVAD patient is life-long and frequent (every 1–4 months at MCSRN centers). The complexities of managing LVAD outpatients are not negligible (lab monitoring, device alarms, equipment maintenance) and are not restricted to daylight hours. As such, staffing requirements for LVAD clinics and inpatient programs are higher than that of general cardiology.11 Although guidelines exist regarding the shared care of heart transplant recipients, the same cannot be said for LVAD recipients.12 Single-center protocols and expert proposals have been created in an attempt to provide the framework within which to propose the optimal care for this challenging patient population, but studies are lacking regarding outcomes.13

Although unadjusted survival is worse in patients who live further from an LVAD implant center, these findings do not support restricting implant to those within a 90 miles radius of an LVAD surgical center. From a practitioner point of view, relocation of patients closer to the LVAD implanting center would seem optimal; however, this is not a realistic option for many patients and their families. Rather, the findings highlight the need for an even greater intensity of remote monitoring for distant LVAD patients. Potential interventions could include improved remote monitoring capabilities such as wireless telemonitoring services similar to those available for defibrillators/pacemakers, reliable ambulatory monitoring of blood pressure in continuous flow LVADs, virtual clinic encounters using live video teleconferencing software and applications, or identifying a local physician who will act as a general care bridge to “lay eyes on patients” between LVAD specialty appointments and to serve as a communication fulcrum with the implanting center. Other options include identifying socioeconomic forces that may limit access to care, such as transportation barriers or frailty of patients or their caregivers.14

Limitations

This study has the limitations inherent to its study design and its retrospective nature. As previously discussed, power may have limited an ability to detect statistical differences in adjusted mortality. Patients living farther from an implant center were older and less likely to be bridged to transplant or transplanted. As such, censoring of patients at the time of transplant may have the results toward those living closer to their implant center. To address this, we controlled for DT intent on multivariable analysis. On a separate analysis of DT patients, distance remained a significant predictor of outcomes (data not shown). This analysis also lacked granular data on other potentially important contributors to patient outcome, including socioeconomic status, access to reliable transportation, insurance statuses, and caregiver support.14 The zip codes used were those at the time of index admission for LVAD implantation and do not account for any change in residence after the surgical hospitalization. Additionally, although the centers included in this analysis are regional destinations for LVAD therapy, they have varying catchment areas with differing patient populations and geographical considerations. The high volume of LVAD implants at these centers must also be taken into account when applying these findings to lower volume institutions.

Conclusions

Patients living farther away from their LVAD implant hospital have 20% worse unadjusted survival than those living within 90 miles. However, adjusted survival differences did not reach statistical significance. As the technology and utilization of LVAD therapy in an increasingly sizable heart failure population grows, a better understanding of the barriers to success for those patients residing further away from implanting LVAD centers is required to improve mortality, morbidity, and the important metrics of quality of life and patient satisfaction. As regionalization of specialized care continues, more frequent remote monitoring and closer partnering with health care systems local to LVAD patients living far from implant may be warranted.

References

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2. Goddard M, Smith P. Equity of access to health care services: theory and evidence from the UK. Soc Sci Med 2001.53: 11491162.
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Keywords:

LVAD; distance; shared care

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