Melissa C. Smallfield

Tolerability and Biological Effects of Long-Acting Octreotide in Patients With Continuous Flow Left Ventricular Assist Devices

Patients with implanted continuous, nonpulsatile, left ventricular assist devices (LVADs) have increased the occurrence of gastrointestinal bleeding (GIB). Although the pathophysiology is multifactorial, there are few treatments beyond supportive care. Octreotide acetate is a somatostatin analog that reduces GIB in various patient populations. However, there are sparse case series that suggest octreotide acetate may reduce GIB in LVAD patients. This 10 patient, 28 week phase I study evaluated the safety and tolerability of octreotide acetate long-acting release (LAR) 20 mg depot injection every 4 weeks until week 16 after LVAD placement. Secondary aims were occurrence of GIB and measurement of vascular endothelial growth factor, fibrinogen, von Willebrand factor, and platelet aggregation across the study period. Ten patients were enrolled, and eight completed the study. The two study dropouts were not related to octreotide. None of the patients experienced side effects or safety concerns related to octreotide nor did GIB occur in the study population. Vascular endothelial growth factor levels were maintained in the reference range throughout the duration of the study. There did appear to be laboratory evidence of acquired von Willebrand syndrome, with mildly low platelet aggregation studies. In conclusion, octreotide acetate LAR 20 mg depot injection was safe and effective in this population.

Surveillance Endomyocardial Biopsy in the Modern Era Produces Low Diagnostic Yield for Cardiac Allograft Rejection.

Background The changing epidemiology of cardiac allograft rejection has prompted many to question the yield of surveillance endomyocardial biopsy (EMB) in heart transplantation (HT) patients. We sought to determine the yield of EMB in the modern era. Methods We evaluated 2597 EMBs in 182 consecutive HT patients who survived to their first EMB. The EMBs were categorized as asymptomatic or clinically driven and were compared based on era of antiproliferative therapy use at our center (early azathioprine era: 1990–2000 vs modern mycophenolate era: 2000–2011). Results In the modern era, patients had a higher prevalence of risk factors for developing rejection (≥ International Society of Heart and Lung Transplantation grade 2R); however, the frequency of rejection was decreased at all times (0–6 months: 60.2% vs 21.5%, P < 0.001, 6–12 months: 26.8% vs 1.8%, P < 0.001, 12–36 months: 32.3% vs 10.5%, P = 0.006). The yield of asymptomatic EMB decreased in the modern era between 0 and 6 months (10.9% vs 3.12%), 6 to 12 months (17% vs 0%), and years 2 to 3 (6.1% vs 1.5%). In the early era, the odds ratio of rejection during asymptomatic EMB compared to a clinically driven EMB was 0.47 (95% confidence interval, 0.31–0.71) and was decreased in the modern era (0.17 [0.07–0.42], P = 0.04). The probability of detecting rejection on asymptomatic EMB was significantly reduced in the modern era, even after adjustment for tacrolimus and induction therapy (1% vs 8%, P < 0.001). Conclusions The clinical yield of surveillance EMB has decreased in the modern era. The EMB in asymptomatic patients longer than 6 months after HT warrants further scrutiny.

Gastrointestinal bleeding in patients with ventricular assist devices is highest immediately after implantation.

Ventricular assist device implantation is associated with gastrointestinal bleeding (GIB); however, outcomes in terms of initial and repeat GIB risk, severity, location of lesions, and endoscopic interventions need to be better defined. Consecutive patients from a database of adult patients with ventricular assist devices (VADs) implanted between January 1, 2000, and December 31, 2010, at a single center were reviewed and followed through May 31, 2011, in a retrospective manner. The GIB events were further classified by severity, lesion location, and lesion type. Hazard analysis models were calculated for the time to GIB events. Of 166 patients with a VAD, 38 patients experienced 84 GIB events. Seventeen patients experienced ≥2 GIB events. Maximal hazard for the first bleeding event was 2.23 events/patient-year at 21 days and declined to the constant hazard by 71 days postimplantation. The hazard for recurrent GIB was greatest immediately after the first GIB event. When considering all GIB events, most lesions (68%) were located in the proximal bowel. Angiodysplasia was the most common lesion type (17.5%) seen on endoscopy when all GIB events were considered, whereas ulcers were the most common type (13.8%) seen in initial GIB events. The actuarial risk of initial GIB events peaks in the first 3 months after VAD implantation followed by a stable lower risk of bleeding. The hazard for recurrent GIB events is substantially increased immediately after the initial GIB.

Impact of INTERMACS Profile on Clinical Outcomes for Patients Supported With the Total Artificial Heart

BACKGROUND Insufficient data delineate outcomes for Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 patients with the total artificial heart (TAH). METHODS We studied 66 consecutive patients implanted with the TAH at our institution from 2006 through 2012 and compared outcome by INTERMACS profile. INTERMACS profiles were adjudicated retrospectively by a reviewer blinded to clinical outcomes. RESULTS Survival after TAH implantation at 6 and 12 months was 76% and 71%, respectively. INTERMACS profile 1 patients had decreased 6-month survival on the device compared with those in profiles 2-4 (74% vs 95%, log rank: P = .015). For the 50 patients surviving to heart transplantation, the 1-year posttransplant survival was 82%. There was no difference in 1-year survival when comparing patients in the INTERMACS 1 profile with less severe profiles (79% vs 84%; log rank test P = .7; hazard ratio [confidence interval] 1.3 [0.3-4.8]). CONCLUSIONS Patients implanted with the TAH as INTERMACS profile 1 had reduced survival to transplantation compared with less sick profiles. INTERMACS profile at the time of TAH implantation did not affect 1-year survival after heart transplantation.

Mechanical Circulatory Support Devices in the ICU

The medical community has used implantable mechanical circulatory support devices at increasing rates for patients dying from heart failure and cardiogenic shock. Newer-generation devices offer a more durable and compact option when compared with bulky early-generation devices. This article is a succinct introduction and overview of the hemodynamic principles and complications after device implantation for ICU clinicians. We review the concepts of device physiology, clinical pearls for perioperative management, and common medical complications after device implantation.

Total Lymphoid Irradiation in Heart Transplantation: Long-Term Efficacy and Survival—An 18-Year Experience

Background. Total lymphoid irradiation (TLI) has been used in transplantation for over 20 years and is currently used in a number of major heart transplant centers as a secondary therapy for recalcitrant recurrent rejection or rejection with hemodynamic compromise. The purpose of this study is to evaluate the long-term risks and efficacy of TLI in the treatment of rejection. Methods. Between 1990 and 1996, 73 adult patients (from 211 adult transplant recipients) received TLI for recurrent rejection (71%), rejection with hemodynamic compromise (25%), and rejection with vasculitis (4%). The treatment consisted of 80 cGy twice per week for 5 weeks. Fifty-five patients received at least 80% of the full dose (>640 cGy). Follow-up ended December 31, 2007, comprising a total 18 year experience. Results. Patients treated with TLI exhibited a short-term decrease in hazard for rejection in the first 12 months posttransplantation (relative risk, 0.36) but exhibited increased cumulative rejection over the long term. There were no differences in the rates of infection, allograft coronary disease, or malignancy, but seven patients developed myelodysplasia or acute myelogenous leukemia, four of those being the rare but uniformly fatal acute megakaryocytic leukemia type 7. Conclusions. Patients treated with TLI seemed to experience a reduction in the early hazard for rejection, but long-term outcomes indicate that such patients continued to accumulate more rejection and rejection-death events, likely because these patients were overall at much higher risk for rejection than the other patient groups. We observed minimal long-term complications, except for the unique occurrence of myelodysplasia and acute megakaryocytic leukemia type 7.

Renal Function Recovery with Total Artificial Heart Support.

Heart failure patients requiring total artificial heart (TAH) support often have concomitant renal insufficiency (RI). We sought to quantify renal function recovery in patients supported with TAH at our institution. Renal function data at 30, 90, and 180 days after TAH implantation were analyzed for patients with RI, defined as hemodialysis supported or an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2. Between January 2008 and December 2013, 20 of the 46 (43.5%) TAH recipients (age 51 ± 9 years, 85% men) had RI, mean preoperative eGFR of 48 ± 7 ml/min/1.73 m2. Renal function recovery was noted at each follow-up interval: increment in eGFR (ml/min/1.73 m2) at 30, 90, and 180 days was 21 ± 35 (p = 0.1), 16.5 ± 18 (p = 0.05), and 10 ± 9 (p = 0.1), respectively. Six patients (30%) required preoperative dialysis. Of these, four recovered renal function, one remained on dialysis, and one died. Six patients (30%) required new-onset dialysis. Of these, three recovered renal function and three died. Overall, 75% (15 of 20) of patients’ renal function improved with TAH support. Total artificial heart support improved renal function in 75% of patients with pre-existing significant RI, including those who required preoperative dialysis.

Device Management and Flow Optimization on Left Ventricular Assist Device Support

The authors discuss principles of continuous flow left ventricular assist device (LVAD) operation, basic differences between the axial and centrifugal flow designs and hemodynamic performance, normal LVAD physiology, and device interaction with the heart. Systematic interpretation of LVAD parameters and recognition of abnormal patterns of flow and pulsatility on the device interrogation are necessary for clinical assessment of the patient. Optimization of pump flow using LVAD parameters and echocardiographic and hemodynamics guidance are reviewed.

Pulmonary Hypertension After Heart Transplantation in Patients Bridged with the Total Artificial Heart.

Pulmonary hypertension (PH) among heart transplant recipients is associated with an increased risk of mortality. Pulmonary hemodynamics improves after left ventricular assist device (LVAD) implantation; however, the impact of PH before total artificial heart (TAH) implantation on posttransplant hemodynamics and survival is unknown. This is a single center retrospective study aimed to evaluate the impact of TAH implantation on posttransplant hemodynamics and mortality in two groups stratified according to severity of PH: high (≥3 Woods units [WU]) and low (<3 WU) baseline pulmonary vascular resistance (PVR). Hemodynamic data were obtained from right heart catheterization performed at baseline (before TAH) and posttransplant at 1 and 12 months. Patients in the high PVR group (n = 12) experienced improvement in PVR (baseline = 4.31 ± 0.7; 1-month = 1.69 ± 0.7, p < 0.001; 12-month = 48 ± 0.9, p < 0.001) and transpulmonary gradient (baseline = 15.8 ± 3.3; 1-month = 11.57 ± 5.0, p = 0.07; 12-month = 8.50 ± 4.0, p = 0.008) after transplantation, reaching similar values as the low PVR group at 12 months. The filling pressures improved in the high PVR group after heart transplantation (HT), but remained elevated. There was no significant difference in survival between the two groups at 12 months follow-up. Patients with high PVR who are bridged to transplant with TAH had improvement in PVR at 12 months after transplant, and the degree of PVR did not impact posttransplant survival.

Safety and Efficacy of Ibutilide in Heart Transplant Recipients

In this report we describe our experience with ibutilide, a relatively new Class III anti-arrhythmic agent, in 8 heart transplant patients with supraventricular tachycardia in various settings (3 patients with rejection, 2 after endomyocardial biopsy). Ibutilide treatment was successful in all patients, with the arrhythmia recurring early in 1 patient. There were no complications.