Abstract Background Small-scale studies focused mainly on nonischemic cardiomyopathy (NICM) have shown that a subset of left ventricular assist device (LVAD) patients can achieve significant ...improvement of their native heart function, but the impact of ischemic cardiomyopathy (ICM) has not been specifically investigated. Many patients with acute myocardial infarction are discharged from their index hospitalization without heart failure (HF), only to return much later with overt HF syndrome, mainly caused by chronic remodeling of the noninfarcted region of the myocardium. Objectives This study sought to prospectively investigate the effect of ICM HF etiology on LVAD-associated improvement of cardiac structure and function using NICM as control. Methods Consecutive patients (n = 154) with documented chronic and dilated cardiomyopathy (ICM, n = 61; NICM, n = 93) requiring durable support with continuous-flow LVAD were prospectively evaluated with serial echocardiograms and right heart catheterizations. Results In patients supported with LVAD for at least 6 months, we found that 5% of subjects with ICM and 21% of subjects with NICM achieved left ventricular ejection fraction ≥40% (p = 0.034). LV end-diastolic and end-systolic volumes and diastolic function were significantly and similarly improved in patients with ICM and NICM. Conclusions LVAD-associated unloading for 6 months resulted in a substantial improvement in myocardial structure, and systolic and diastolic function in 1 in 20 ICM and 1 in 5 NICM patients. These specific incidence and timeline findings may provide guidance in clinical practice and research design for sequencing and prioritizing advanced HF and heart transplantation therapeutic options in patients with ICM and NICM.
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.
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.
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.
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.
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.
The United Network for Organ Sharing database was queried for cardiac transplants, comparing characteristics and outcomes for PPCM, other women, and all others.
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).
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.
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.
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.
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%.
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.
Little is known about mixed cellular and antibody-mediated rejection (MR) in heart transplantation. It remains unclear whether cardiac MR has distinctive pathologic and clinical features beyond those ...of simultaneous cellular rejection (CR) and antibody-mediated rejection (AMR). In this study we systematically explore the pathologic and clinical characteristics of MR in heart transplantation.
The UTAH Cardiac Transplant Program database was queried for transplant recipients who survived long enough to have at least one endomyocardial biopsy (EMB) between 1985 and 2014. Only EMBs with both CR and AMR scores documented were included. In addition to detailed pathologic analyses, we also examined the incidence and prevalence of MR, the likelihood to transition from and to MR, and mortality associated with MR.
Patients (n = 1,207) with a total of 28,484 EMBs met the study inclusion criteria. The overall prevalence of MR was 7.8% and it was nearly twice as frequent within the first year post-transplant. Mild MR was by far the most common occurrence and was typically preceded by an immune active state. When CR increased in severity, AMR tended to follow, but the reverse was not true. On pathology, individual features of CR and AMR were more easily separated in cases of mild MR, whereas they substantially overlapped in more severe cases. MR was associated with a significant cardiovascular death risk that was incremental with severity.
MR is not common, usually occurs early after transplant, and is associated with worse outcomes. MR reflects a complex interplay between cellular and humoral processes, which varies with rejection severity.
There is greater awareness of the pathologic features and clinical implications of antibody-mediated rejection (AMR) after heart transplantation (HT). Yet, compared with adults, the lack of routine ...surveillance for AMR has limited the growth of evidence in the pediatric population. Herein, we compared outcomes of pediatric HT recipients with and without AMR.
All recipients ≤18 years of age with at least 1 endomyocardial biopsy (EMB) between 1988 and 2009 were included in this study. Assessment for AMR was routine. AMR severity was assigned retrospectively using the proposed 2011 ISHLT grading schema for pathologic AMR (pAMR). Outcome comparisons were made between patients with histologic and immunopathologic evidence for AMR (pAMR 2), those with severe AMR (pAMR 3), and those without evidence of AMR (pAMR 0) or without both histologic and immunopathologic findings (pAMR 1).
Among 1,406 EMBs, pAMR 2 or higher was present in 258 (18%), occurring in 45 of 76 (59%) patients. Of the 17 episodes of pAMR 3 in 9 patients, 6 (35%) were sub-clinical. Mortality was not different between groups. Patients with at least 1 pAMR 3 episode had lower freedom from cardiovascular (CV) mortality or cardiac allograft vasculopathy within 5 years of HT than those without pAMR 3 (45% vs 91%, p < 0.001).
Biopsy findings of AMR (pAMR 2 or higher) are common after pediatric HT. Like cellular rejection, biopsy grading of AMR seems important to delineate those at risk of adverse events. Our results suggest that pAMR 3 is associated with worse CV outcomes. Widespread surveillance for pAMR with a uniform grading system is an important next step to further validate these findings in the pediatric HT population.
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 > or =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.
The Intermountain Risk Score (IMRS), composed of the complete blood count (CBC) and basic metabolic profile (BMP), predicts mortality and morbidity in medical and general populations. Whether ...longitudinal repeated measurement of IMRS is useful for prognostication is an important question for its clinical applicability.
Females (N = 5,698) and males (N = 5,437) with CBC and BMP panels measured 6 months to 2.0 years apart (mean 1.0 year) had baseline and follow-up IMRS computed. Survival analysis during 4.0±2.5 years (maximum 10 years) evaluated mortality (females: n = 1,255 deaths; males: n = 1,164 deaths) and incident major events (myocardial infarction, heart failure HF, and stroke).
Both baseline and follow-up IMRS (categorized as high-risk vs. low-risk) were independently associated with mortality (all p<0.001) in bivariable models. For females, follow-up IMRS had hazard ratio (HR) = 5.23 (95% confidence interval CI = 4.11, 6.64) and baseline IMRS had HR = 3.66 (CI = 2.94, 4.55). Among males, follow-up IMRS had HR = 4.28 (CI = 3.51, 5.22) and baseline IMRS had HR = 2.32 (CI = 1.91, 2.82). IMRS components such as RDW, measured at both time points, also predicted mortality. Baseline and follow-up IMRS strongly predicted incident HF in both genders.
Repeated measurement of IMRS at baseline and at about one year of follow-up were independently prognostic for mortality and incident HF among initially hospitalized patients. RDW and other CBC and BMP values were also predictive of outcomes. Further research should evaluate the utility of IMRS as a tool for clinical risk adjustment.
The use of continuous-flow left ventricular assist devices (LVAD) have markedly improved outcomes in patients with advanced heart failure (HF). The HeartWare LVAD is a miniaturized centrifugal pump ...implanted within the pericardial space. Implantable cardioverter-defibrillators (ICDs) are susceptible to oversensing of extracardiac signals (electromagnetic interference EMI). We report two cases of EMI in patients that received a HeartWare LVAD as destination therapy for advanced HF. The patients were 75 and 78 years old, both with severe ischemic dilated cardiomyopathy (ejection fraction < 0.20) and New York Heart Association class 4 heart failure. Both patients had a St. Jude Medical Unify ICD with a 7 Fr dual coil St. Jude Medical Durata ICD lead. In both patients, the lead location was in the right ventricular apex with an inferior orientation. Both patients experienced immediate ICD therapies after LVAD placement, requiring the tachytherapies to be disabled. ICD programming changes to increase sensitivity and the detection windows were ineffective. Both patients underwent ICD system revision. In one patient, the existing lead was moved to an anteroseptal location that stopped the EMI. In the other patient, the ICD system was changed to allow a separate right ventricular sensing lead in an anteroseptal location and a dual coil ICD lead placed in an apical location, a strategy used to obtain an acceptable defibrillation threshold. The patients have had no subsequent EMI detected on clinical and remote monitoring. Patients with a right ventricular apical ICD lead placement that undergo placement of a HeartWare LVAD are susceptible to EMI and inappropriate ICD therapies. These cases suggest the primary mechanism is proximity of the ICD lead to the device and as such relocation to an anteroseptal location can overcome the problem. These data suggest that all patients that receive a HeartWare LVAD with an ICD should have the device carefully checked at maximum LVAD output to determine if EMI may be present. ASAIO Journal 2013;59:136-139. Key Words: left ventricular assist device, electromagnetic interference, improper ICD shocks, end-stage heart failure.
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).
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).
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.
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.
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