Impact of Postoperative Liver Dysfunction on Survival After Left Ventricular Assist Device Implantation.

BACKGROUND: Liver dysfunction in left ventricular assist device (LVAD) recipients is common both before and after implantation. Postoperative liver dysfunction (PLD) develops in some LVAD recipients without preoperative liver dysfunction. The aim of this study was to assess clinical outcomes in such patients. METHODS: Records of all patients undergoing implantation of a HeartMate II (HM II, St. Jude Medical, Inc, Minneapolis, MN) LVAD at a single center at the University of Minnesota from January 2005 through June 2014 were analyzed. PLD was defined by hypertransaminasemia or hyperbilirubinemia, or both, during the hospitalization for LVAD implantation. RESULTS: During the study period, 284 patients underwent HM II implantation. Excluded from analysis were 14 recipients with preoperative liver dysfunction. In the final cohort (n = 270), there were no major difference in preoperative characteristics among those patients with versus without PLD. PLD developed in 129 (47.8%) recipients: 16 (12.4%) had isolated hypertransaminasemia (group I), 76 (58.9%) had isolated hyperbilirubinemia (group II), and 37 (28.7%) had combined hypertransaminasemia and hyperbilirubinemia (group III). Group III LVAD recipients had significantly greater rates of 30-day, 90-day, and 1-year mortality, along with significantly higher transfusion requirements and higher rates of renal replacement therapy, prolonged ventilation, and vasopressor use. Moreover, their mortality risk was significantly higher than that of PLD-free LVAD recipients (hazard ratio, 4.6; 95% confidence interval, 2.1 to 10.1; p < 0.001). CONCLUSIONS: Isolated hyperbilirubinemia is common after LVAD implantation. In this study, it was not associated with an increase in early or midterm postoperative mortality. However, postoperative combined transaminasemia and hyperbilirubinemia was associated with a significant increase in early and midterm morbidity and mortality. Further research into the pathogenesis of post-LVAD PLD is necessary.

Clinical implications of donor age: A single-institution analysis spanning 3 decades.

BACKGROUND: We sought to clarify the effect of donor age as a continuous variable on morbidity and mortality in a single-institution experience. METHODS: From 1986 to 2016, 882 adult lung transplants were performed, including 396 in the lung allocation score era. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association of donor age with overall survival and bronchiolitis obliterans syndrome (BOS) score ≥1-free survival. Logistic regression was used to evaluate the association with primary graft dysfunction grade 3. Natural cubic splines were used to explore donor age in a continuous fashion to allow for nonlinear relationships. RESULTS: In the lung allocation score era, unadjusted 5-year survival was not significantly different between 3 a priori-defined donor age groups: age <40, 40 to 54, and age ≥55 years (64%, 61%, and 69%, P = .8). Unadjusted 5-year freedom from BOS ≥1 was not significantly different (34%, 20%, and 33%, respectively, P = .1). After we adjusted for comorbidities, cubic spline analysis demonstrated no effect between donor age as a continuous variable and hazard for mortality at 5 years. Similarly, no interaction was seen between donor age and risk of BOS or primary graft dysfunction 3. Adjusted analysis of all 882 transplants pre- and postinception of the lung allocation score also showed no effect of age on 10-year survival. CONCLUSIONS: Long-term survival of lung transplant recipients was not affected by the age of the donor. These findings support the notion that donor age could be relaxed.

Infective endocarditis, embolic stroke and splenic abscess: a case report.

We present the case of a patient presenting with embolic stroke secondary to aortic valve endocarditis, additionally complicated by splenic abscess, successfully treated by emergent valve replacement followed by delayed, robotic splenectomy.

Gender differences in long-term survival post-transplant: A single-institution analysis in the lung allocation score era.

The purpose of this study was to clarify the significance of recipient gender status on lung transplant outcomes in a large single-institution experience spanning three decades, we analyzed data from all lung transplants performed in our institution since 1986. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate the effect of recipient characteristics on survival and BOS score ≥1-free survival. Logistic regression analysis was used to explore the association of gender with short-term graft function. About 876 lung transplants were performed between 1986 and 2016. Kaplan-Meier survival estimates at 5 years post-transplant for females vs males in the LAS era were 71% vs 58%. In the LAS era, females showed greater unadjusted BOS≥1-free survival than males (35% vs 25%, P=.02) over 5 years. Female gender was the only factor in the LAS era significantly associated with improved adjusted 5-year survival [HR 0.56 (95% CI 0.33, 0.95) P=.03]. Conversely, in the pre-LAS era female gender was not associated with improved survival. Female recipients showed significantly improved survival over 5 years compared to males in the LAS era. A prospective analysis of biologic and immunologic differences is warranted.

Aortic insufficiency in continuous-flow left ventricular assist device support patients is common but does not impact long-term mortality.

BACKGROUND: Aortic insufficiency (AI) is a significant long-term complication of continuous-flow left ventricular assist device (CF-LVAD) implantation. We sought to evaluate its impact on clinical outcomes and mortality in CF-LVAD recipients. METHODS: We retrospectively analyzed 237 patients implanted with HeartMate II CF-LVADs at our institution from June 2005 through June 2013. We evaluated recipients' baseline characteristics and annual echocardiograms, grading AI severity as either none, trace, mild, moderate or severe. Only moderate or severe AI was considered clinically significant. Recipients who underwent concomitant aortic valve surgery or who had undergone previous prosthetic aortic valve implantation were excluded. RESULTS: Moderate or severe AI occurred in 32 (15.2%) patients. Risk factors that significantly affected the development of AI included older age at the time of implantation, female gender, longer duration of LVAD support and destination therapy designation. Freedom from moderate or severe AI was 94%, 76% and 65% of patients at 1, 3 and 5 years, respectively. Overall cohort survival based on Kaplan-Meier analysis was 78%, 59% and 42% at 1, 3 and 5 years, respectively. There was no difference in survival between recipients who developed significant AI and those who did not (log-rank test, p = 0.73). CONCLUSIONS: In this large, single-institution study, the overall rate of AI was low, but increased in frequency with longer duration of LVAD support. Although AI development remains a concern for patients on long-term CF-LVAD support, AI development does not appear to impact long-term mortality.

A Decade of Experience With Continuous-Flow Left Ventricular Assist Devices.

The use of continuous-flow left ventricular assist devices (CF-LVADs) has revolutionized the landscape of mechanical circulatory support for patients with heart failure. Clinical trials are already testing the next generation of CF-LVADs. In this study, our objective was to review our long-term experience with the current generation of CF-LVADs, specifically, the HeartMate (HM) II (Thoratec Corp, Pleasanton, CA). In this single-center retrospective analysis, we evaluated the records of 278 consecutive patients who underwent a total of 302 HM II placements from June 2005 through June 2014. We excluded 11 patients from our final study group, who had previously undergone placement of a HM XVE that failed. We divided the remaining 267 patients into 3 equal groups of 89 patients each, by time period: group 1, June 2005 through May 2009; group 2, June 2009 through January 2012; and group 3, February 2012 through June 2014. To examine differences in survival between our 3 groups, we used time-to-event analysis, including the Kaplan-Meier method. To examine secondary outcomes (including stroke, hemolysis, gastrointestinal bleeding, pump thrombus, and transplant), we used one-way analysis of variance. For our final study group of 267 patients, the total follow-up time was 479.01 patient-years (median, 469 days). The mean age of patients was 57 years; 81.4% were male. In all, 209 (78.9%) patients underwent HM II placement as a bridge to transplant; 58 (21.1%), as destination therapy (DT). The overall survival rate was 94% at 30 days, 77% at 1 year, 65% at 2 years, 60% at 3 years, 50% at 4 years, and 48% at 5 years. In bridge to transplant patients, the survival rate was 78% at 1 year and 66% at 2 years; in DT patients, 70% and 60%. In group 1 patients, the survival rate was 94% at 30 days, 64% at 1 year, and 48% at 2 years; in group 2, 93%, 88%, and 76%; and in group 3, 94%, 77%, and 73% (P = 0.003). In the later years of our study period, from June 2009 onwards (ie, in groups 2 and 3), we noted a statistically significant increase in HM II placement as DT, a reduction of driveline infections, increasing pump exchange, increasing hemolysis, a reduced frequency of transplants, and an improved survival rate (as compared with the earlier group 1). The HM II has favorably influenced the outcomes of patients with end-stage heart failure, yet major complications still limit their survival. Improving compatibility between the pump and the individual host patient, enhancing anticoagulation strategies, and developing a totally implantable pump might further reduce complications thereby improving survival times and allowing CF-LVAD placement to be a true long-term alternative to a heart transplant.

Gastrointestinal Bleeding during Continuous-Flow Left Ventricular Assist Device Support is Associated with Lower Rates of Cardiac Transplantation.

Gastrointestinal bleeding (GIB) remains a significant problem after continuous-flow left ventricular assist device (CF-LVAD) implantation. We hypothesized that the subsequent need for blood transfusions in patients with GIB may reduce rates of cardiac transplantation. We performed a retrospective review of 232 patients implanted with the HeartMate II (HM II) CF-LVAD from June 2005 through May 2013 at our center to determine risk factors for GIB and assess its effect on cardiac transplantation. Over a total LVAD follow-up time of 364 person-years, 62 GIB episodes occurred in 49 patients (27%), for an event rate of 0.45 gastrointestinal bleeds/patient-year of LVAD support. Women made up 15% of our cohort, yet contributed 29% of the GIB (p = 0.06). Survival at 6 month, 1 year, and 2 years was not statistically different in patients who developed GIB and those who did not (77% vs 78%, 74% vs 71%, and 61% vs 54%, respectively). In transplant-eligible patients, GIB was associated with a 27% lower rate of cardiac transplantation (rate ratio 0.73, p < 0.05). Although the mechanism behind this finding is unclear, GIB appears to be linked to higher transfusion rates, which may cause the development of subsequent allosensitization.

The Recovery of Hibernating Hearts Lies on a Spectrum: from Bears in Nature to Patients with Coronary Artery Disease.

Clinicians often use the term "hibernating myocardium" in reference to patients with ischemic heart disease and decreased function within viable myocardial regions. Because the term is a descriptor of nature's process of torpor, we provide a comparison of the adaptations observed in both conditions. In nature, hearts from hibernating animals undergo a shift in substrate preference in favor of fatty acids, while preserving glucose uptake and glycogen. Expression of electron transport chain proteins in mitochondria is decreased while antioxidant proteins including uncoupling protein-2 are increased. Similarly, hibernating hearts from patients have a comparable metabolic signature, with increased glucose uptake and glycogen accumulation and decreased oxygen consumption. In contrast to nature however, patients with hibernating hearts are at increased risk for arrhythmias, and contractility does not fully recover following revascularization. Clearly, additional interventions need to be advanced in patients with coronary artery disease and hibernating myocardium to prevent refractory heart failure.

Echocardiographic Ramp test for continuous-flow left ventricular assist devices: do loading conditions matter?

OBJECTIVES: This study investigated whether continuous AI and/or elevated mean arterial pressure (MAP) were associated with false positive results for flow obstruction in echocardiographic ramp speed tests in patients with a continuous-flow left ventricular assist device. BACKGROUND: Failure to reduce the left ventricular end-diastolic diameter (LVEDD) with increasing device speeds in a ramp test is predictive of pump obstruction. Aortic insufficiency (AI) or increased MAP can diminish the ability to unload the left ventricle. METHODS: LVEDD was plotted against device speed, and a linear function slope was calculated. A flat LVEDD slope (≥-0.16) was considered abnormal (suggestive of obstruction). Ramp test results were compared in patients with or without either AI or increased MAP at baseline speed, and receiver-operator characteristic (ROC) curves were constructed for predictors of device obstruction. Device thrombosis was confirmed by direct visualization of clot at explantation or on inspection by the manufacturer. RESULTS: Of 78 ramp tests (55 patients), 36 were abnormal (18 true positive, 18 false positive), and 42 were normal (37 true negative, 5 false negative). In patients with AI, LVEDD slope was -0.14 ± 0.17, which was consistent with device obstruction (vs. -0.25 ± 0.11 in patients without AI; p < 0.001), despite no difference in mean lactate dehydrogenase concentration between the 2 groups (1,301 ± 1,651 U/l vs. 1,354 ± 1,365 U/l; p = 0.91). Area under the ROC curve (AUC) for LVEDD slope was 0.76 and improved to 0.88 after removal of patients with AI from the study. LVEDD slope in patients with MAP ≥85 mm Hg was similar to that for device obstruction (-0.18 ± 0.07) and was abnormal in 6 of the 12 ramp tests performed. Combining LVEDD slope with lactate dehydrogenase concentration increased the AUC to 0.96 as an indicator of device obstruction. CONCLUSIONS: Abnormal loading conditions due to AI or elevated MAP may result in false positive ramp tests.

Anti-factor Xa and activated partial thromboplastin time measurements for heparin monitoring in mechanical circulatory support.

OBJECTIVES: This study investigated the relationship between anti-factor Xa (anti-FXa) and activated partial thromboplastin time (aPTT) for monitoring intravenous unfractionated heparin (IV-UFH) in patients with continuous-flow left ventricular assist devices (CF-LVADs). BACKGROUND: CF-LVADs have become mainstream therapy for patients with advanced heart failure. Thromboembolic events, device thrombosis, and bleeding continue to be a challenge with this technology. Adequate anticoagulation is required to prevent these adverse events. METHODS: A prospective study of consecutive patients implanted with a CF-LVAD was conducted. Paired samples were considered concordant if aPTT values fell into expected ranges for subtherapeutic, therapeutic, and supratherapeutic anti-FXa levels. Heparin dosing was on the basis of anti-Xa levels. RESULTS: A total of 340 paired values from 38 patients were evaluated. Anti-FXa and aPTT were discordant in 253 samples (74.4%), with a high degree of variability in aPTT for any given anti-FXa level (r(2) = 0.57). Results were discordant in 104 samples (63.8%) from patients undergoing bridging therapy with warfarin and in 149 samples (84.2%) from patients with device obstruction and/or hemolysis (p < 0.001). The most common pattern of discordance was a supratherapeutic aPTT value despite a therapeutic anti-FXa level (49.1% for bridging vs. 75.8% for device obstruction and/or hemolysis; p < 0.001). CONCLUSIONS: Levels of aPTT were disproportionately prolonged relative to the corresponding anti-FXa levels in CF-LVAD patients, particularly those with device obstruction. Hemolysis and warfarin administration may falsely elevate aPTT, resulting in overestimation of heparin concentration and under-anticoagulation. Use of aPTT and anti-FXa to guide heparin therapy may lead to different estimates of heparin concentration in the same patient.

Mitochondrial fusion proteins in revascularized hibernating hearts.

BACKGROUND: Hibernating myocardium is characterized by viable yet dysfunctional myocardium secondary to chronic ischemia, with studies demonstrating incomplete early recovery after coronary artery bypass graft (CABG). We tested whether mitochondrial fusion proteins, an indicator of mitochondrial biogenesis, are increased in hibernating myocardium post-CABG. METHODS: A constrictor was placed on the left anterior descending (LAD) artery of nine pigs. Four of these pigs additionally underwent CABG 12 wk later with a left internal mammary artery graft to the LAD distal to the constrictor. Five pigs had a constrictor placed but did not undergo CABG (Hib). Five pigs did not have a constrictor placed (control). Computerized tomography angiography was used to confirm stenosis at the site of constrictor placement and patency of left internal mammary artery grafts. Regional blood flows were determined at baseline and during 40 µg/kg/min dobutamine infusion. Mitochondrial proteins were quantified by Western blot. RESULTS: Blood flow in the LAD region after CABG was lower than remote regions during dobutamine infusion (2.54 ± 0.24 versus 3.46 ± 0.33 mL/min/g; P < 0.05). Electron transport chain proteins were ∼70% lower in Hib compared with those in control and failed to normalize after CABG. Post-CABG, PGC1α nuclear-bound content was increased compared with Hib (9.02 ± 0.48 versus 5.54 ± 0.98 arbitrary units, respectively; P < 0.05), and expression of mitofusins-1 and 2 and optic atrophy-1 more than doubled. CONCLUSIONS: PGC1α and mitochondrial fusion proteins are increased 4 wk post-CABG in hibernating hearts, indicating mitochondrial fusion has begun to occur and signaling early mitochondrial recovery. Future studies should address changes in maximal myocardial oxygen consumption relative to mitochondrial protein expression.

Recovery of hibernating myocardium: what is the role of surgical revascularization?

Myocardial responses to chronic ischemia represent a continuum of adaptations resulting, over time, in a stress-resistant phenotype. One such adaptation, hibernating myocardium (HM), has increased antioxidant capacity that protects against ischemia-induced oxidative stress. Studies have suggested that revascularization alone may not fully restore cardiac function, highlighting the need for targeted therapies to serve as adjuncts to the innate healing process following revascularization. In our review, we discuss current understanding of HM and the recovery process following surgical revascularization, focusing on animal models of HM to understand implications for human patients.

Expression of uncoupling protein-2 remains increased within hibernating myocardium despite successful coronary artery bypass grafting at 4 wk post-revascularization.

BACKGROUND: We have previously shown that mitochondrial uncoupling protein-2 (UCP-2) is increased in a swine model of hibernating myocardium (HM). Although UCP-2 reduces oxidant stress, it can promote inefficiency of the electron transport chain. In this study, we tested whether UCP-2 remains increased in revascularized HM (RHM) after coronary artery bypass grafting (CABG). METHODS: Seven swine underwent thoracotomy with placement of a constrictor on the left anterior descending artery (LAD). Twelve weeks later, a left internal mammary artery graft was placed on the distal LAD. Four weeks post-CABG, computed tomography angiography documented patent grafts and function. At the terminal study, blood flow to the LAD and remote territories were assessed during high dose dobutamine and mitochondria isolated from both regions for analysis. Comparisons were made to a group of swine with HM who underwent constrictor placement without bypass grafting (n = 4). RESULTS: During dobutamine infusion, RHM demonstrated lower blood flows (2.44 ± 0.23 versus 3.43 ± 0.30 mL/min/g; P < 0.05) and reduced wall thickening (33 ± 9% versus 52 ± 13%; P < 0.05) compared with remote regions. RHM had lower respiratory control indices (3.7 ± 0.3 versus 4.3 ± 0.4; P < 0.05) with persistently increased UCP-2 content. CONCLUSIONS: Despite patent grafts, RHM demonstrates a submaximal response to dobutamine infusion and increased mitochondrial UCP-2 expression. These data support the notion that recovery of the mitochondria in RHM is delayed early post-CABG and may contribute to impaired oxygen consumption and contractile reserve during catecholamine challenges.

Gastrointestinal bleed after left ventricular assist device implantation: incidence, management, and prevention.

BACKGROUND: Continuous-flow left ventricular assist devices (CF-LVADs) have become the standard of care for patients with end-stage heart failure (HF). While these devices have improved durability compared to earlier generation left ventricular assist devices (LVADs), increased frequency in some complications has been seen, including gastrointestinal bleeding (GIB), pump thrombosis and hemolysis. We discuss the incidence, management and prevention of GIB after CF-LVAD implantation. METHODS: We reviewed the current literature available on the incidence, management and prevention of GIB after CF-LVAD implantation with a focus on our experience at the University of Minnesota, with data on nearly 300 patients who received a CF-LVAD from 2005 to 2013. RESULTS: The incidence of GIB after CF-LVAD varies between 18-40% in numerous studies. At the University of Minnesota, out of 233 patients who underwent HeartMate II (HMII) implantation between 2005-2013, 60 GIB episodes occurred in 51 patients (22%), with an event rate of 0.17 gastrointestinal bleeds/patient-year of support. The etiology of GIB appears to be multifactorial. The main factors which have been identified include the need for chronic anticoagulation, acquired von Willebrand syndrome, platelet dysfunction and increased incidence of arteriovenous malformations due to chronic low pulse pressure. When managing an LVAD patient with GIB, a multi-disciplinary approach is needed. The main goals of treatment are evaluating the location and severity of the bleed, holding anti-coagulants and resuscitation to maintain stable hemodynamics. CONCLUSIONS: GIB is a complication with considerable morbidity. Future efforts to further understand the etiology of GIB and optimize anti-coagulation are needed to improve outcomes following CF-LVAD implantation.

Left ventricular assist devices as a bridge to cardiac transplantation.

Heart failure remains a significant cause of morbidity and mortality, affecting over five million patients in the United States. Continuous-flow left ventricular assist devices (LVAD) have become the standard of care for patients with end stage heart failure. This review highlights the current state of LVAD as a bridge to transplant (BTT) in patients requiring mechanical circulatory support (MCS).

Retained catheter dilator in right ventricular outflow tract for 22 years.

We report the case of a 61-year-old male with a retained catheter dilator in the right ventricular outflow tract for over 22 years. The management of retained intravascular foreign objects in the myocardium is reviewed.

Who's covering our loved ones: surprising barriers in the sign-out process.

BACKGROUND: The aims of this study were to characterize obstacles affecting current sign-out practices and to evaluate the potential impact of standardized sign-out guidelines. METHODS: In June 2011, detailed guidelines for transitions of care were implemented, and a 29-item multiple-choice survey was developed to assess sign-out practices, attitudes, and barriers to effective communication. Surveys were administered to residents and nurses at 3 time points. Comparisons between time points were assessed using t tests and χ(2) tests (α = .05). RESULTS: Guideline implementation achieved nonsignificant improvements in satisfaction with sign-outs, perceptions of patient safety, adequacy of information provided in sign-out, and patient knowledge by on-call residents. On follow-up, concerns surfaced regarding less complete sign-out processes due to new duty-hour restrictions. CONCLUSIONS: Guideline implementation mildly improved perceptions of safety and adequacy of sign-out; however, persistent barriers to continuity of care remain. Sign-out standardization may not adequately ensure patient safety, and further efforts to improve handoff processes are in need.

Impact of childhood inguinal hernia repair in adulthood: 50 years of follow-up.

BACKGROUND: Short-term follow-up of pediatric inguinal herniorrhaphies has yielded low morbidity and recurrence rates. Nonetheless, the impact of childhood inguinal herniorrhaphy on the adulthood risk for repeat groin operation, chronic groin pain, and infertility has not been established. STUDY DESIGN: A survey was mailed to all patients who underwent a primary inguinal hernia repair as a child at our institution from 1956 to 1960. The survey inquired about repeat groin operation, chronic groin pain, and fertility status. Demographic and operative information from respondents was obtained from medical record review. RESULTS: Of 332 eligible patients, 213 (66%) responded to the survey, accounting for 252 inguinal herniorrhaphies (174 unilateral, 33 bilateral, and 6 sequential contralateral). All hernias were indirect, more common on the right (right, 49%; left, 25%; bilateral, 26%), with males predominating (91%). History of premature birth was present in 5 (2%) patients. High ligation of the hernia sac was performed in 90% of the repairs. Hydrocelectomy was performed in 25 (13%) and orchidopexy in 37 (19%) patients. With a median follow-up of 49 years (range 47.2 to 52.1 years), a total of 21 (8.4%) repeat and 13 (6%) contralateral groin operations were observed. Chronic groin pain and a medical diagnosis of infertility were reported by 7 (3%) and 10 (5%) patients, respectively. CONCLUSIONS: Childhood inguinal hernia repairs do not appear to decrease or increase the risk of inguinal hernia development in adulthood. Parents and children undergoing a childhood inguinal hernia repair should be informed that although the risk for a true indirect hernia recurrence is low, the risk of repeat groin operation (8.4%) and chronic groin pain (3%) remain present in adulthood.