Christopher T. Holley

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.

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.

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.

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.

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.

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.

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).

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.

Magnetic resonance imaging assessment of cardiac function in a swine model of hibernating myocardium 3 months following bypass surgery

Objective: Clinical studies demonstrate delayed recovery of hibernating myocardium (HM) following coronary artery bypass graft (CABG) surgery. Cardiac magnetic resonance (CMR) imaging is effective in identifying HM in clinical settings. Our animal model of HM shows partial but incomplete functional recovery 1 month following CABG using echocardiography. This study uses CMR imaging to determine completeness of recovery 3 months post‐CABG. Methods: Swine (N = 12) underwent left anterior descending artery (LAD) 1.5‐cm constrictor placement creating a territory of HM over 12 weeks. CMR at 12 weeks confirmed hibernation without infarction (N = 12). Off‐pump left internal thoracic artery (LITA) to the LAD was performed in 9 animals. Three animals were killed as HM controls. CMR imaging was repeated in revascularized animals before death at 1 (n = 4) or 3 months (n = 5). CMR imaging was performed at baseline and with dobutamine infusion (5 &mgr;g/kg/min). Results: Twelve weeks after constrictor placement, CMR imaging confirmed viability in LAD region and LAD stenosis in all animals. In HM, wall thickening is reduced at baseline but with contractile reserve present during dobutamine infusion. Following revascularization, CMR imaging confirmed patent LITA graft (n = 9). Analysis of baseline regional function shows incomplete recovery of HM following CABG, with reduced contractile reserve at both 1 and 3 months post‐CABG. Conclusions: CMR imaging provides accurate spatial resolution of regional contractile function and confirms the presence of HM at 12 weeks following instrumentation of the LAD. Three months following CABG, partial recovery of HM with contractile reserve is present in the single LAD territory.

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

Abstract 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.