During the last decade, the number of patients undergoing LVAD implantation for end-stage heart failure has markedly increased. Advances in device design, patient selection, and surgical experience have led to improved outcomes1–5; however, early readmission (defined as within 30 days) after LVAD implantation remains common. It negatively affects quality of life, is associated with increased healthcare costs, and, among the heart failure population, is associated with increased mortality.6–8
Previous LVAD studies have described pre- and postoperative risk factors for 30 day readmission and the financial costs; however, those studies included only small numbers of patients and were not powered to assess the impact of 30 day readmission on subsequent mortality. The only previous study to assess the impact of 30 day readmission on longer-term outcomes was a small, single-center study: it demonstrated a trend toward increased mortality.9 Perhaps 30 day readmission after LVAD implantation is a marker for a poor trajectory, including increased mortality, during mechanical support.
In this study, we sought to determine the causes of readmission, whether or not 30 day readmission was associated with increased mortality after LVAD implantation and to better understand the relationship between readmission and the rate of subsequent cardiac transplants.
Materials and Methods
The University of Minnesota institutional review board approved this retrospective analysis. Included in our study were 277 patients who were ≥18 years old when they underwent first-time continuous-flow LVAD implantation at our institution and who survived to hospital discharge. Our study period was 2005 through 2015. During this time period, there were no formal changes to our patient selection policy.
The baseline characteristics collected from the time of LVAD implantation included age, gender, type of cardiomyopathy, Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile, device type, creatinine, total bilirubin concentration, body mass index, and smoking history. The comorbidities collected included diabetes, hypertension, previous cardiothoracic surgery, and chronic obstructive pulmonary disease (COPD). We defined COPD either by a previous diagnosis or by a forced expiratory volume in 1 second of < 70% of the predicted value at the time of LVAD implantation. In addition, we noted whether LVAD implantation was a bridge-to-transplant (BTT) or destination therapy (DT). We also recorded baseline hemodynamic values, such as cardiac output and index, heart rate, right atrial pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure (PCWP). Pulmonary vascular resistance was calculated as mean pulmonary artery (PA) pressure minus PCWP divided by cardiac output (Wood units). Pulmonary artery compliance was approximated using the stroke volume divided by PA pulse pressure (ml·mm Hg−1).10,11 Pulmonary artery pressure index was calculated by using the following formula: (pulmonary artery systolic pressure − pulmonary artery diastolic pressure)/mean right atrial pressure. Preoperative Model for End Stage Liver Disease Excluding INR (MELD-XI) scores were calculated in the following way: MELD-XI = 5.11 × ln (serum bilirubin in mg/dl) ± 11.76 × ln (serum creatinine in mg/dl) ± 9.44 (REF).
Postoperative variables collected included the length of hospital stay, number of ventilator days, and length of vasopressor use. In-hospital complications including gastrointestinal (GI) bleeding and stroke were captured using INTERMACS definitions.12 Stroke and transient ischemic attacks (TIA) were defined as any new, temporary or permanent focal, or global neurological deficit ascertained by a standard neurological examination. Events were coded as a TIA if deficits fully reversed within 24 hours and if imaging was negative for infarction. Events were coded as a stroke if neurologic deficits lasted longer than 24 hours or if infarction was detected by imaging. Gastrointestinal bleeding was defined as any packed red blood cell transfusion more than 7 days after LVAD placement accompanied by clinical signs of GI bleeding. From the hospital discharge summaries, we extracted the primary reason for each 30 day readmission.
The primary outcome was all-cause mortality. From our chart review, we obtained vital status (current through October 2015). For patients who were still alive at the end of follow-up, we recorded the date of their last clinic visit. The secondary outcome was the cardiac transplant rate among BTT patients.
To perform all of our statistical analyses, we used STATA 13 (College Station, TX).
To compare baseline characteristics between the two groups—i.e., patients who were readmitted within 30 days versus those who were not—we used the Student’s t-test for normally distributed variables; the Wilcoxon rank-sum test, for nonnormally distributed continuous variables. For categorical variables, we used the Pearson χ2 test or Fisher’s exact test, where appropriate. In addition, we compared postoperative variables between the two groups.
To obtain survival estimates, we performed Kaplan–Meier survival analyses. To compare survival between the two groups, we used the log-rank test. To assess the impact of 30 day readmission on mortality, we used a Cox proportional hazards regression model. We tested covariates and then chose them on the basis of postulated associations and significance, per our univariate exploratory analysis (p < 0.2). To arrive at a final adjusted model, we incorporated covariates in a forward and backward stepwise fashion, using the likelihood ratio test for significance.
To assess the impact of 30 day readmission on the cardiac transplant rate, we calculated the incidence rate ratios for transplants among BTT patients in each of the two groups.
For all analyses, we considered a probability value of less than 0.05 as significant.
Of the 277 patients in our entire cohort, 221 (79.7%) were male; 217 (78.3%) were BTT patients. The median follow-up time was 563 days (interquartile range, 258–1139 days). Ischemic cardiomyopathy was the cause of heart failure in 154 (55.5%) of the patients. Ninety-two percent of the pumps in this cohort were HeartMate II devices (256/277) and 8% (21/277) were HVAD.
Of the 277 patients, 76 (27.4%) patients were readmitted within 30 days; the other 201 (72.6%) were not. The baseline characteristics of those two groups are compared in Table 1. Male gender, previous smoking, and a higher baseline creatinine level were each associated with 30 day readmission. There were no HVAD patients readmitted within 30 days (0/21) versus 30% of all HeartMate II patients (76/256), p < 0.05.
With regard to postoperative complications, patients who were readmitted within 30 days were more likely to have experienced, while still hospitalized for their LVAD implantation, GI bleeding, or strokes. Specifically, 23 (30.2%) of the 76 patients who were readmitted experienced GI bleeding before their initial hospital discharge, as compared with only 29 (14.4%) of the 201 patients who were not readmitted. Similarly, 16 (21%) of the 76 patients who were readmitted experienced strokes before their initial hospital discharge, as compared with only 16 (7.9%) of the 201 patients who were not readmitted. Other postoperative complications did not significantly differ between the two groups; the median hospital lengths of stay before LVAD and after LVAD implant were also similar (Table 2).
Reasons for Readmission
The reasons for 30 day readmission in the 76 patients are shown in Table 3. The most common reason for readmission was a cardiac-related complication, in 28 (37%) of the 76 patients who were readmitted—followed by bleeding in 15 (20%) and then by a LVAD-related issue (e.g., a lactic dehydrogenase [LDH] rise, power surges) in 14 (18%). Of the 28 patients readmitted for a cardiac issue, 18 (64%) had fluid overload, 6 (21%) had arrhythmia, and 4 (14%) had presyncope or syncope. Of note, 7 patients (9.2%) were readmitted because of infection and 2 patients (2.6%) were readmitted because of transient ischemic attacks. The remaining 10 patients were readmitted for a variety of other reasons.
There was no significant difference detected (p = 0.77) in baseline creatinine among patients readmitted for volume overload (mean: 1.48 mg/dl; standard deviation [SD]: 0.54) compared with patients readmitted for other causes (mean: 1.55 mg/dl; SD: 0.70). Among the patients readmitted for a GI bleed, there was no significant difference (p = 0.96) in baseline hemoglobin (mean: 11.2 g/dl; SD: 2.1) compared with patients readmitted for other causes (mean: 11.2 g/dl; SD: 1.9).
Survival, Mortality, and Transplant Rates
The two groups—i.e., patients who were readmitted within 30 days versus those who were not—significantly differed in terms of the survival rate at 6 months (87% vs. 94%), at 1 year (82% vs. 88%), and at 2 years (67% vs. 78%). The difference in survival was statistically significant over the full length of follow-up (log-rank p = 0.019; Figure 1). In our univariate Cox model, increased mortality was also associated with 30 day readmission (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.08–2.71; p = 0.02).
In our final multivariate model, increased mortality was still associated with 30 day readmission (HR, 1.60; 95% CI, 1.1–2.5; p = 0.04). We adjusted that model for age, BTT versus DT status, diabetes, COPD, INTERMACS profile, type of cardiomyopathy, and albumin level. Among the 217 BTT patients, the cardiac transplant rate was similar between the 2 groups: 18.7 transplants per patient-year among those who were readmitted within 30 days versus 19.7 transplants per patient-year among who were not (p = 0.26).
Our results demonstrate that 30 day readmission after LVAD implantation is not only common but also a marker for increased mortality during mechanical support. Even after we adjusted for potential confounders, the association between 30 day readmission and increased mortality persisted. Risk factors for readmission included male gender, previous smoking, a higher baseline creatinine level, higher MELD-XI score, and postoperative GI bleeding or stroke. There was also a signal of HVAD patients having a lower risk of readmission however the sample size was very small. Thirty day readmission, however, was not associated with a lower cardiac transplant rate among BTT patients.
Previous studies of readmission in the LVAD population have highlighted the causes and financial costs.2,13–16 Our study includes the largest number of continuous-flow LVAD patients to date in such a study; moreover, we focused on the impact of 30 day readmission on clinical outcomes after LVAD implantation. The only other study, to our knowledge, that focused on 30 day readmission9 demonstrated a readmission rate of 26.1%—a rate very similar to ours (27.4%). That study noted an interesting, but statistically nonsignificant, trend toward increased mortality among patients readmitted within 30 days. In contrast, we found a statistically significant association between 30 day readmission and increased mortality, possibly because our study had twice the number of patients.
In our study, an LDH rise or power surge was the reason for readmission in 18% of our readmitted patients. An LDH rise within 30 days has been well described as a marker for pump thrombosis; furthermore, evidence supports an association with increased morbidity and mortality.17,18 The data from the PREVENT (PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management) trial19 are encouraging: the rate of 30 day hemolysis and pump thrombosis have decreased with improved pump positioning during surgery, with higher pump speeds, and with better anticoagulation strategies (including a higher international normalized ratio goal and bridging with heparin). There is also hope that, with the newer-generation pumps, the adverse impact of pump thrombosis on mortality will decrease as a result of better hemocompatibility.
We were intrigued by the impact on readmission by GI bleeding (a postoperative complication experienced by many LVAD patients before their initial hospital discharge). It is unclear how much this complication drove the increased mortality among readmitted patients. Older age, a lower hemoglobin level, and DT status have all been identified as risk factors for GI bleeding,20–22 yet we remain unable to predict risk factors for recurrent GI bleeding after LVAD implantation. As a community, we need better prediction models, as we would likely not recommend LVAD implantation to patients with a high enough risk for this outcome and were not eligible for a cardiac transplant. Further, these patients may be considered for less aggressive anticoagulation strategies. In our study, the cardiac transplant rate was similar among BTT patients who were versus were not readmitted, which suggests that many of them were able to recover from the setback of 30 day readmission.
We believe that more careful selection of patients and better timing of LVAD implantation might decrease perioperative complications; efforts to reduce readmission might also have a favorable impact. It may be that patients with higher level of acuity before implantation such as those with higher MELD-XI scores, lower INTERMACS profiles, or those who experience in-hospital complications should be considered for a more aggressive remote monitoring strategy upon discharge to try and prevent further early complications. Multicenter data are needed to better understand risk factors for readmission and to optimize strategies for reducing readmission.
Our single-center study has the inherent limitations of a retrospective analysis. Even though we adjusted for potential confounders of the relationship between 30 day readmission and mortality, unmeasured variables could have contributed to residual confounding. Given our study’s relatively small sample size, we are unable to address which cause of readmission (fluid overload, GI bleeding, pump thrombosis/LDH rise, or stroke) is the most predictive of negative long-term outcomes. We were also unable to comment on the relationship between early readmission and subsequent adverse event rates as not all adverse events for of our LVAD patients are captured in our dataset.
Among our study patients, 30 day readmission after LVAD implantation was frequent and was associated with increased mortality. It is currently unclear whether the general health of those patients (e.g., comorbidities) was a factor and whether efforts to reduce 30 day readmission would favorably affect longer-term patient outcomes. These findings require validation in a larger dataset.
The authors thank Mary E. Knatterud, PhD, for assistance in the preparation of this article.
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