Deborah Budge

Red cell distribution width, C-reactive protein, the complete blood count, and mortality in patients with coronary disease and a normal comparison population.

BACKGROUND Red cell distribution width (RDW) is associated with morbidity and mortality in coronary artery disease (CAD), but the connection of RDW with chronic inflammation is equivocal. METHODS In 1,489 patients with CAD and 8.4-15.2 years of follow-up all-cause mortality and RDW were studied using Cox regression. RDW and its associations with inflammation, liver function, renal function, and body mass were assessed. A population of 449 normal (No-CAD) patients also was evaluated. RESULTS RDW predicted all-cause mortality in a step-wise manner (HR=1.37 per quintile; 95% CI=1.29, 1.46; p-trend<0.001). A significant but meaningless correlation between RDW and high-sensitivity C-reactive protein (hsCRP) was identified (r=0.181; p<0.001). With full adjustment, RDW remained significant (p-trend<0.001) and the strongest predictor of mortality among all factors included in the model. RDW also strongly predicted all-cause mortality in the normal control population (HR=1.33 per quintile, CI=1.15, 1.55; p-trend<0.001), but hsCRP did not predict mortality among normal controls. CONCLUSIONS RDW was associated with mortality in patients with CAD and may provide clinically useful prognostication. Although RDW was correlated with hsCRP, they were independent predictors of mortality. RDW has been incorporated into risk prediction tool using data from basic chemistries available at: http://intermountainhealthcare.org/IMRS.

End-of-life decision making and implementation in recipients of a destination left ventricular assist device

BACKGROUND The use of left ventricular assist devices (LVADs) as destination therapy (DT) is increasing and has proven beneficial in prolonging survival and improving quality of life in select patients with end-stage heart failure. Nonetheless, end-of-life (EOL) issues are inevitable and how to approach them underreported. METHODS Our DT data registry was queried for eligible patients, defined as those individuals who actively participated in EOL decision making. The process from early EOL discussion to palliation and death was reviewed. We recorded the causes leading to EOL discussion, time from EOL decision to withdrawal and from withdrawal to death, and location. Primary caregivers were surveyed to qualify their experience and identify themes relevant to this process. RESULTS Between 1999 and 2009, 92 DT LVADs were implanted in 69 patients. Twenty patients qualified for inclusion (mean length of support: 833 days). A decrease in quality of life from new/worsening comorbidities usually prompted EOL discussion. Eleven patients died at home, 8 in the hospital and 1 in a nursing home. Time from EOL decision to LVAD withdrawal ranged from <1 day to 2 weeks and from withdrawal until death was <20 minutes in all cases. Palliative care was provided to all patients. Ongoing assistance from the healthcare team facilitated closure and ensured comfort at EOL. CONCLUSIONS With expanding indications and improved technology, more DT LVADs will be implanted and for longer durations, and more patients will face EOL issues. A multidisciplinary team approach with protocols involving DT patients and their families in EOL decision making allows for continuity of care and ensures dignity and comfort at EOL.

Obesity and Left Ventricular Assist Device Driveline Exit Site Infection

Driveline exit site (DLES) infection is a persistent problem among the left ventricular assist device (LVAD) patients. This study investigated the relationship between obesity and DLES infection. Records of LVAD patients at two institutions from January 1999 to January 2009 were queried. Results were analyzed using t tests. Those with LVAD support ≥90 days were included. The body mass index (BMI) of each patient was measured at the time of implant and at the conclusion of LVAD support or currently, if the patient was ongoing. Other data included preimplant age, ejection fraction, blood urea nitrogen, creatinine, diabetes, New York Heart Association class, pulmonary capillary wedge pressure, VO2 max, and inotrope therapy. The 118 patients who qualified for the study were placed in an infection group (n = 36) or in the control group (n = 82). Both groups had similar preimplant characteristics. Variables with differences statistically significant between the groups included duration of LVAD support, indication for support, device type, and BMI. Patients who developed DLES infections had a significantly higher BMI and continued weight gain over the course of LVAD therapy compared with the control group. Although this association requires further study, implications for clinical practice may include the provision of nutrition and exercise counseling for patients undergoing LVAD therapy, especially if overweight. These results may warrant increased measures to prevent and treat infection in the preimplant and postimplant periods.

Would access to device therapies improve transplant outcomes for adults with congenital heart disease? Analysis of the United Network for Organ Sharing (UNOS)

BACKGROUND Patients with congenital heart disease (CHD) now survive into adulthood and often present with end-stage heart failure (HF). HF management and approach to orthotopic heart transplant (OHT) may differ from adults without CHD. We sought to compare OHT waitlist characteristics and outcomes for these 2 groups. METHODS The Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database was used to identify adults (≥18 years) listed for OHT from 2005 to 2009. The cohort was divided into those with or without CHD. RESULTS Of 9,722 adults included, 314 (3%) had CHD. Adults with CHD were younger (35 ± 13 vs 52 ± 12 years, p < 0.01) and more often had undergone prior cardiac surgery (85% vs. 34%, p < 0.01). Patients with CHD were less likely to have a defibrillator (44% vs 75%, p < 0.01) or ventricular assist device (5% vs 14%, p < 0.01) and were more likely to be listed at the lowest urgency status than patients without CHD (64% vs 44%, p < 0.01). Fewer CHD patients achieved OHT (53% vs 65%, p < 0.001). Although overall waitlist mortality did not differ between groups (10% vs 8%, p = 0.15), patients with CHD were more likely to experience cardiovascular death (60% vs 40%, p = 0.03), including sudden in 44% and due to HF in 16%. CONCLUSIONS Despite lower urgency status, patients with CHD have greater cardiovascular mortality awaiting OHT than those without. Increased defibrillator use could improve survival to OHT, because sudden death is common. VAD support may benefit select patients, but experience in CHD is limited. Referral to specialized adult congenital heart centers can enhance utilization of device therapies and potentially improve waitlist outcomes.

Genome-Wide Significance and Replication of the Chromosome 12p11.22 Locus Near the PTHLH Gene for Peripartum Cardiomyopathy

Background— Peripartum (PP) cardiomyopathy (CM) is a rare condition of unknown etiology that occurs in late pregnancy or early postpartum. Initial evidence suggests that genetic factors may influence PPCM. This study evaluated and replicated genome-wide association of single nucleotide polymorphisms with PPCM. Methods and Results— Genome-wide single nucleotide polymorphisms in women with verified PPCM diagnosis (n=41) were compared separately with local control subjects (n=49 postmenopausal age-discordant women with parity ≥1 and no heart failure) and iControls (n=654 women ages 30 to 84 years with unknown phenotypes). A replication study of independent population samples used new cases (PPCM2, n=30) compared with new age-discordant control subjects (local2, n=124) and with younger control subjects (n=89) and obstetric control subjects (n=90). A third case set of pregnancy-associated CM cases not meeting strict PPCM definitions (n=29) was also studied. In the genome-wide association study, 1 single nucleotide polymorphism (rs258415) met genome-wide significance for PPCM versus local control subjects (P=2.06×10−8; odds ratio [OR], 5.96). This was verified versus iControls (P=7.92×10−19; OR, 8.52). In the replication study for PPCM2 cases, rs258415 (ORs are per C allele) replicated at P=0.009 versus local2 control subjects (OR, 2.26). This replication was verified for PPCM2 versus younger control subjects (P=0.029; OR, 2.15) and versus obstetric control subjects (P=0.013; OR, 2.44). In pregnancy-associated cardiomyopathy cases, rs258415 had a similar effect versus local2 control subjects (P=0.06; OR, 1.79), younger control subjects (P=0.14; OR, 1.65), and obstetric control subjects (P=0.038; OR, 1.99). Conclusions— Genome-wide association with PPCM was discovered and replicated for rs258415 at chromosome 12p11.22 near PTHLH. This study indicates a role of genetic factors in PPCM and provides a new locus for further pathophysiological and clinical investigation.

Peripartum cardiomyopathy: post-transplant outcomes from the United Network for Organ Sharing Database.

BACKGROUND Nearly 25% of patients with peripartum cardiomyopathy (PPCM) will require cardiac transplantation. Whether post-transplant outcomes differ among patients with PPCM compared with other recipients remains unsettled. METHODS The United Network for Organ Sharing database was queried for cardiac transplants, comparing characteristics and outcomes for PPCM, other women, and all others. RESULTS Between 1987 and 2010, 42,406 patients (9,419 women and 32,987 men) received a heart transplant. Of these, 485 women who had PPCM as the indication were younger (p < 0.001), had higher sensitization (p < 0.001), required higher intensity of cardiovascular support pre-transplant (p = 0.026), and had higher listing status (p < 0.001). Those with PPCM had more post-transplant rejection during the index transplant hospitalization (p < 0.001) and during the first year (p = 0.003). Comparing PPCM with other women and all others, graft survival was inferior (p = 0.004 and p < 0.003, respectively) and age-adjusted survival was lower (p < 0.001 and p = 0.02, respectively). CONCLUSIONS This large report shows outcomes of graft failure and death are inferior for recipients with PPCM, which may be partly explained by younger age, higher allosensitization, higher pre-transplant acuity, and increased rejection. More research is needed to determine management strategies to improve outcomes in PPCM heart transplant recipients.

A longitudinal study of the course of asymptomatic antibody-mediated rejection in heart transplantation

BACKGROUND Growing evidence suggests worse cardiac allograft vasculopathy and mortality in patients with asymptomatic antibody-mediated rejection (AMR). Debate continues about whether therapeutic intervention is warranted to avoid adverse outcomes. In this study we examine the course of individual episodes of untreated asymptomatic AMR on follow-up endomyocardial biopsy (EMB). METHODS The U.T.A.H. Cardiac Transplant Program database was queried for transplant recipients between 1985 and 2009 who survived beyond 1 year and had at least 1 episode of lone AMR with a follow-up EMB. All EMBs were screened for AMR by immunofluorescence and graded for severity. Data were analyzed based on time from transplant (early, ≤12 months; late, >12 months). RESULTS Nine hundred fifty-eight patients with a total of 15,448 biopsies qualified for the study. Average age at transplant was 46.7 years; 13% of the patients were female. Within the first year post-transplant, asymptomatic AMR was diagnosed in 13.6% of biopsies compared with 5.2% beyond 1 year. AMR resolved in 65% (early) vs 75% (late) on follow-up EMB. More severe AMR was less likely to improve regardless of time from transplant. Furthermore, after an episode of AMR had resolved, the recurrence rate at 3, 6 and 12 months was 44%, 50.1% and 56.2%, respectively. CONCLUSIONS The incidence of AMR is higher in the first year post-transplant and the likelihood of resolution is less on follow-up EMB, especially when more severe. A small but significant number of cases became worse or did not change. These new findings may be helpful in planning future studies that test whether therapeutic interventions on asymptomatic AMR favorably impact outcomes.

The impact of bridge-to-transplant ventricular assist device support on survival after cardiac transplantation

OBJECTIVE To determine the impact of bridge-to-transplant ventricular assist device support on survival after cardiac transplantation. METHODS From January 1, 1993, to April 30, 2009, a total of 525 cardiac transplants were performed. Ventricular assist devices were placed as a bridge to transplant in 110 patients. We focused our analysis on the 2 most common causes of end-stage heart failure requiring transplantation: idiopathic dilated cardiomyopathy (n = 201) and coronary artery disease (n = 213). Data including gender, age, date of transplant, cause of heart failure, prior heart transplant, placement of a ventricular assist device, type of ventricular assist device, and panel-reactive antibody sensitization were analyzed to derive Kaplan-Meier survival probabilities and multivariable Cox regression models. RESULTS In patients with idiopathic dilated cardiomyopathy who received a ventricular assist device as a bridge to transplant, survival was decreased at 1 year (P = .008) and 5 years (P = .019), but not at 10 years, posttransplant. In patients with coronary artery disease, the use of a ventricular assist device as a bridge to transplant did not influence survival at 1, 5, and 10 tears posttransplant. In patients with idiopathic dilated cardiomyopathy who received a Heartmate I (Thoratec Corp, Pleasanton, Calif) ventricular assist device as a bridge to a cardiac transplant, elevation in the pretransplant panel-reactive antibody correlated with a decrease in long-term survival. CONCLUSION In patients with idiopathic dilated cardiomyopathy, placement of a Heartmate I ventricular assist device as a bridge to a cardiac transplant is associated with an elevation in the pretransplant panel-reactive antibody and a decrease in 1- and 5-year survivals after cardiac transplantation.

Automated identification and predictive tools to help identify high-risk heart failure patients: pilot evaluation

OBJECTIVE Develop and evaluate an automated identification and predictive risk report for hospitalized heart failure (HF) patients. METHODS Dictated free-text reports from the previous 24 h were analyzed each day with natural language processing (NLP), to help improve the early identification of hospitalized patients with HF. A second application that uses an Intermountain Healthcare-developed predictive score to determine each HF patients risk for 30-day hospital readmission and 30-day mortality was also developed. That information was included in an identification and predictive risk report, which was evaluated at a 354-bed hospital that treats high-risk HF patients. RESULTS The addition of NLP-identified HF patients increased the identification scores sensitivity from 82.6% to 95.3% and its specificity from 82.7% to 97.5%, and the models positive predictive value is 97.45%. Daily multidisciplinary discharge planning meetings are now based on the information provided by the HF identification and predictive report, and clinicians review of potential HF admissions takes less time compared to the previously used manual methodology (10 vs 40 min). An evaluation of the use of the HF predictive report identified a significant reduction in 30-day mortality and a significant increase in patient discharges to home care instead of to a specialized nursing facility. CONCLUSIONS Using clinical decision support to help identify HF patients and automatically calculating their 30-day all-cause readmission and 30-day mortality risks, coupled with a multidisciplinary care process pathway, was found to be an effective process to improve HF patient identification, significantly reduce 30-day mortality, and significantly increase patient discharges to home care.

Differential impact on post‐transplant outcomes between pulsatile‐ and continuous‐flow left ventricular assist devices

Ventura PA, Alharethi R, Budge D, Reid BB, Horne BD, Mason NO, Stoker S, Caine WT, Rasmusson B, Doty J, Clayson SE, Kfoury AG. Differential impact on post‐transplant outcomes between pulsatile‐ and continuous‐flow left ventricular assist devices.
Clin Transplant 2011: 25: E390–E395.