B. Louis

Noninvasive assessment of left ventricular assist devices with cardiovascular computed tomography and impact on management

BACKGROUND Left ventricular assist devices (LVADs) provide a bridge to recovery or heart transplantation but require serial assessment. Echocardiographic approaches may be limited by device artifact and acoustic window. Cardiovascular computed tomography (CCT) may provide improved non-invasive imaging of LVADs. We evaluated the diagnostic findings and clinical impact of CCT for non-invasive assessment of patients with LVADs. METHODS CCT examinations performed between 2005 and 2008 in patients with LVADs were identified. Acquisitions were completed on the identical 64-detector-row scanner with intravenous contrast administration. Electrocardiographic gating was used in patients with pulsatile devices, and peripheral pulse gating was used in patients with continuous-flow devices. Comparison was made between CCT results and 30-day outcomes, including echocardiographic and intraoperative findings. RESULTS We reviewed 32 CCT examinations from 28 patients. Indications included evaluation of low cardiac output symptoms, assessment of cannula position, low flow reading on the LVAD, and surgical planning. CCT identified critical findings in 6 patients, including thrombosis and inlet cannula malposition, all confirmed intraoperatively. CCT missed 1 case of intra-LVAD thrombus. Using intraoperative findings as the gold standard, CCTs sensitivity was 85% and specificity was 100%. Echocardiographic LVAD evaluation did not correlate with findings on CCT (kappa = -0.29, 95% confidence interval, -0.73 to 0.13). CONCLUSIONS This preliminary observational cohort study indicates that non-invasive imaging using CCT of LVADs is feasible and accurate. CCT warrants consideration in the initial evaluation of symptomatic patients with LVADs.

Placement of Long-term Implantable Ventricular Assist Devices Without the Use of Cardiopulmonary Bypass

BACKGROUND Implantation of ventricular assist devices for cardiac support is normally performed using cardiopulmonary bypass. Post-operative complications could be minimized by the placement of these devices without the use of cardiopulmonary bypass. METHODS We hypothesize that left ventricular assist devices (LVADs), in selected patients, can be implanted safely off-pump. RESULTS In 25 patients, LVADs were implanted off-pump (mean age 50 years; 64% male, 36% female; average left ventricular ejection fraction 15%). Pre-operatively 68% of patients were on inotropes, 25% had an intra-aortic ballon pump, and 44% had a previous sternotomy. Blood utilization intra- and post-operatively was relatively minimal with 1 re-exploration for bleeding. There were 3 deaths. CONCLUSIONS We describe a technique for successful placement of a left ventricular assist device without the use of cardiopulmonary bypass.

Intrathymic inoculation of donor bone marrow induces long-term acceptance of lung allografts

BACKGROUND We investigated whether intrathymic inoculation of donor bone marrow at the time of transplantation induced long-term acceptance of lung allografts. METHODS Four- to-six-week-old August Copenhagen Irish (ACI) and Wistar Furth (WF) rats were used as donors and recipients, respectively. After being inoculated intrathymically with either donor-specific (ACI) or third-party (F344) bone marrow (2.0 x 10(7) cells/lobe), the recipient (WF) animal received a left lung transplant from an ACI donor. A short course of tacrolimus (1 mg/kg per day for 5 days) was administered. Animals were sacrificed at timed intervals after transplantation, and rejection was graded on a scale of 0 (none) to 4 (severe). RESULTS At 28 days, animals receiving donor-specific bone marrow have lower (p < 0.01) median rejection grade (MRG = 0.25; n = 6) than those receiving third-party bone marrow (MRG = 3; n = 6) and controls (no bone marrow; MRG = 2.5; n = 6). Animals receiving intrathymic donor bone marrow accepted lung allografts up to 380 days with minimal rejection (MRG = 2; n = 6). Long-term lung recipients also accepted a challenging donor-specific heart graft (n = 4) for more than 150 days. In mixed lymphocyte reaction assays, T lymphocytes of WF recipients that had received intrathymic bone marrow (from ACI donor) exhibited low response (similar to self antigens) to donor (ACI) cells, but reacted strongly (five times higher) to third-party (F344) cells. CONCLUSIONS Intrathymic inoculation of donor bone marrow at the time of transplantation along with a short course of tacrolimus induces long-term acceptance of lung allografts in rats. This simple approach of tolerance induction may have clinical application.

Fulminant Neisseria meningitidis: role for extracorporeal membrane oxygenation.

Invasive meningococcal disease is often associated with complications of septic shock and central nervous system dysfunction. Extracorporeal membrane oxygenation is more commonly being used for respiratory failure and sepsis, but neurologic injury and potential coagulopathy are often considered relative contraindications. We report a successful case of complicated Neisseria meningitidis septic shock with disseminated intravascular coagulopathy requiring extracorporeal support.

Extracorporeal Membrane Oxygenation for Pandemic (H1N1) 2009

To the Editor: As the world struggles with the challenges of influenza A pandemic (H1N1) 2009, it is clear that treatment options for critically ill infected patients are suboptimal because deaths continue to be reported in otherwise young and healthy patients. Extracorporeal membrane oxygenation (ECMO) is an established therapeutic option for patients with medically refractory cardiogenic or respiratory failure. We describe the successful use of ECMO in a patient with complicated pneumonia and influenza A pandemic (H1N1) 2009 virus infection. Our patient, a 21-year-old woman who was 4 months postpartum, had poorly controlled insulin-dependent diabetes (hemoglobin A1C level 13.2 mg/dL). She sought treatment at another hospital after 3 days of respiratory symptoms, a productive cough after working in her garden, and a fever >103°F. Her condition rapidly deteriorated, and she required mechanical ventilation, vasoactive medications, and drotecogin-α (Xigris; Eli Lilly and Company, Indianapolis, IN, USA) for profound shock. The patient was then transferred to Ohio State University Medical Center on August 24, 2009; at admission she exhibited hypotension (83/43 mm Hg) and tachycardia (159 bpm), despite having received high doses of vasoactive medications (norepinephrine 1.0 µg/kg/min, phenylephrine 2.0 µg/kg/min). A transthoracic echocardiograph showed severe biventricular failure (ejection fraction 5%–10%); peak tropinin level was 6 mg/dL. Arterial blood gas confirmed metabolic acidosis (pH 7.12, partial carbon dioxide pressure [pCO2] 48 mm Hg, pO2 117 mm Hg, HCO3 15.3 mmol/L). Despite fluid resuscitation and administration of epinephrine (0.06 µg/kg/min), her condition failed to improve, and she was given femoral vein–femoral artery ECMO. A comprehensive search for infectious causes was undertaken. Treatment with broad-spectrum empiric antimicrobial drugs such as linezolid (Pfizer, Inc, New York, NY, USA), piperacillin/tazobactam (Wyeth, Madison, NJ, USA), and doxycycline (Pfizer, Inc) and the antiviral drug oseltamivir (Tamiflu; Roche Laboratories Inc., Nutley, NJ, USA), 150 mg 2×/d, was started. Respiratory cultures were positive for methicillin-sensitive Staphylococcus aureus and Aspergillus glaucus. Nafcillin and voriconazole were added to the treatment regimen. PCR of a bronchoalveolar lavage specimen later identified pandemic (H1N1) 2009 virus. The patient was weaned from ECMO on hospital day (HD) 10 and extubated on HD11. Repeat cardiovascular evaluation showed normal biventricular function and no coronary disease. She was discharged from hospital for rehabilitation on September 15, 2009 (HD 22), with an oxygen saturation of 98% on room air and is now fully recovered. The use of ECMO is an established option for patients with medically refractory acute and reversible cardiopulmonary failure (Table) (1–3). For isolated respiratory failure, veno–veno support can be used by femoral vein to femoral vein or femoral vein to right internal jugular vein cannulation. With concomitant cardiogenic shock, veno–arterial cannulation may be required with cannulation of the right internal jugular or femoral vein for outflow, and for inflow, the femoral artery directly or the axillary artery by a surgically placed side graft. Central venous (right atrium) and arterial (ascending aorta) cannulation is an option but requires median sternotomy. Table Relative indications and contraindications for extracorporeal membrane oxygenation* This case is not the first reported use of ECMO for respiratory failure secondary to viral pneumonia (4), and recently, ECMO was used with limited success for complications of pandemic (H1N1) 2009 (5). Its broader use in treating critically ill patients has been limited, however, because ECMO requires substantial institutional and multidisciplinary commitment for implementation and is typically only available at major medical centers offering cardiovascular surgery. Although we cannot say specifically why our patient survived, clearly, aggressive and comprehensive empiric treatment, physiologic support, and close multidisciplinary communication were vital to managing the condition of this critically ill patient. ECMO may have assisted in organ recovery and patient survival. However, further studies should be conducted to critically evaluate ECMO in the armamentarium of therapeutic options for severe pandemic (H1N1) 2009 respiratory failure.

Profound thrombocytopenia with glycoprotein IIb/IIIa inhibitors plus heparin for pump thrombus.

espite aggressive anti-coagulation, thrombotic compliations of rotary long-term ventricular assist devices emain a formidable challenge. Recently, Thomas reorted successful treatment with tirofiban, a glycoproein IIb/IIIa inhibitor. In response, we report a case of cute left ventricular assist device (LVAD) thrombosis nd a concern for glycoprotein IIb/IIIa inhibitor–inuced thrombocytopenia with worsening thrombosis. Our patient, a 61-year-old man underwent implantaion of a HeartMate II LVAD as a bridge to transplant for evere ischemic cardiomyopathy. His initial post-operaive course was uncomplicated and his anti-thrombotic egimen consisted of warfarin (4 mg/day, goal Internaional Normalized Ratio [INR] 2 to 3), aspirin (81 g/day) and persantine (75 mg three times daily). On ay 196 post-implant he was admitted with a 2-week istory of dark urine. Laboratory studies suggested VAD-induced hemolysis (Table 1). Pump flows were .0 liters/min and power was 9.0 watts (normal 7.5 atts), consistent with VAD thrombosis. He was started n eptifibatide (Integrilin; Schering-Plough), dosed at 2 g/kg/min for 84 hours, and heparin (goal activated artial thromboplastin time [aPTT] 57 to 70 seconds) rips. Within 17 hours after discontinuing the eptifiatide, severe thrombocytopenia developed (Figure 1) nd all anti-platelet agents were stopped. His pump ower remained elevated and serum creatinine inreased from 1.07 to 3.25 mg/dl. Platelet factor (PF)-4 nd aggregation assays were positive suggestive of eparin-induced thrombocytopenia (HITs). A direct hrombin inhibitor, argatroban, was started and within everal days his platelet count normalized as did renal unction, pump flows and power and lactate dehydroenase (LDH). Long-term warfarin dose was increased goal INR: 2.5 to 3.5) and clopidogrel was started (75 g/day).

Aging and transplant arteriosclerosis in absence of alloreactivity and immunosuppressive drugs in a rat aortic model: recipient age's contribution.

Background. Almost half of all transplanted vascularized organ grafts will be lost to transplant arteriosclerosis sometime posttransplantation. Organ shortage for primary transplants and retransplants has led to donor-pool expansion to include elderly donors, knowing that aging per se promotes arteriosclerosis. The current understanding that donor age negatively affects organ and/or patient survival outcome is undermined by variables such as the use of immunosuppressive drugs, their toxicity to the graft, degree of donor-recipient histocompatibility, and the resulting chronic rejection. The purpose of this study was to determine whether the donor’s age or recipient’s age matters the most in transplant arteriosclerosis in the absence of such variables. Methods. A syngeneic combination was used where young (2-month-old) and old (22-month-old) donor aortas were injured to initiate neointimal thickening, then transplanted into age-mismatched recipients for 14, 60, and 90 days and then assessed for neointimal thickening. Base level injury response due ischemia and surgery was evaluated in age-matched and noninjured aortic grafts, respectively. Results. Young aortas invariably developed thicker neointima when transplanted into old recipients than when transplanted into young ones. Correspondingly, old aortas transplanted in young recipients consistently developed less neointimal thickening than when transplanted into old recipients. Conclusions. Our findings strongly suggest that the severity of age-related neointima formation is primarily determined by the recipient’s age rather than the donor’s age. Therefore, in addition to focusing on donor-specific tolerance induction, strategies aiming at increasing the lifespan of vascularized organ grafts also have to take into consideration the recipient’s aging milieu.

Long-term mechanical support for complex left ventricular postinfarct pseudoaneurysms.

Left ventricular free wall rupture can be a catastrophic problem. Although small lacerations can be managed with various techniques of primary closure, larger and more complex defects can be difficult to treat. We present and discuss 2 cases of chronic, complex ventricular pseudoaneurysms managed successfully with long-term mechanical support.