Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI.

Essentials Relationship of acquired von Willebrand disease (VWD) and platelet dysfunction is explored. Patients with ventricular assist devices and on extracorporeal membrane oxygenation are investigated. Acquired VWD and platelet receptor shedding is demonstrated in the majority of patients. Loss of platelet adhesion receptors glycoprotein (GP) Ibα and GPVI may increase bleeding risk. SUMMARY: Background Ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are associated with bleeding that is not fully explained by anticoagulant or antiplatelet use. Exposure of platelets to elevated shear in vitro leads to increased shedding. Objectives To investigate whether loss of platelet receptors occurs in vivo, and the relationship with acquired von Willebrand syndrome (AVWS). Methods Platelet counts, coagulation tests and von Willebrand factor (VWF) analyses were performed on samples from 21 continuous flow VAD (CF-VAD), 20 ECMO, 12 heart failure and seven aortic stenosis patients. Levels of platelet receptors were measured by flow cytometry or ELISA. Results The loss of high molecular weight VWF multimers was observed in 18 of 19 CF-VAD and 14 of 20 ECMO patients, consistent with AVWS. Platelet receptor shedding was demonstrated by elevated soluble glycoprotein (GP) VI levels in plasma and significantly reduced surface GPIbα and GPVI levels in CF-VAD and ECMO patients as compared with healthy donors. Platelet receptor levels were also significantly reduced in heart failure patients. Conclusions These data link AVWS and increased platelet receptor shedding in patients with CF-VADs or ECMO for the first time. Loss of the platelet surface receptors GPIbα and GPVI in heart failure, CF-VAD and ECMO patients may contribute to ablated platelet adhesion/activation, and limit thrombus formation under high/pathologic shear conditions.

Outcomes following de novo CNI-free immunosuppression after heart transplantation: a single-center experience.

Renal impairment at the time of heart transplantation complicates the choice of subsequent immunosuppressive therapy. Calcineurin (CNI)-free regimens utilizing proliferation signal inhibitors (PSI) may mitigate against nephrotoxicity in this group; however, their effectiveness remains unclear. We present our 7-year experience with de novo CNI-free, PSI-based immunosuppression after heart transplantation. Of the 152 patients transplanted between July 1999 and July 2006, de novo immunosuppression regimens were 49 CNI-free, PSI-based, 88 CNI, 15 combination of CNI+PSI. Pretransplant creatinine clearance improved within 6 months in the PSI group (0.69 +/- 0.34 mL/s vs. 1.00 +/- 0.54 mL/s, p < 0.05) but not the CNI (1.32 +/- 0.54 mL/s vs. 1.36 +/- 0.53 mL/s, p = ns) or CNI+PSI (1.20 +/- 0.24 mL/s vs. 1.20 +/- 0.41 mL/s, p = ns) groups. The PSI group had more episodes of early (

Post-cardiac transplantation gout: incidence of therapeutic complications.

OBJECTIVE: To study the clinical impact of gout treatment following cardiac transplantation. METHODS: We performed an audit of all cardiac transplant recipients of the Alfred Hospital before August 1998 who lived in Victoria. RESULTS: We studied 225 patients (81% men), with a mean post-transplant follow-up of 50.8 months (SD 36). Forty-three (19%) had pre-transplant gout, 19 recurring post-transplantation. Twenty-three patients developed gout de novo. Of the 24 patients who received allopurinol, 6 developed pancytopenia and required hospitalization. Fourteen received a change in immunosuppression: in 5 patients following pancytopenia, and in 9 to enable safe use of allopurinol. Thirty-two patients received colchicine; 5 developed neuromyopathy. Impaired renal function, diuretic use, and hypertension were more common in this sub-group. Non-steroidal anti-inflammatory agents, used in 16 patients, caused serious complications in 1 patient (life-threatening peptic ulceration and hemorrhage, precipitating dialysis-dependent chronic renal failure). CONCLUSIONS: Cardiac transplant recipients, when treated for gout, are at high risk of therapeutic complications. Thus, gout treatment significantly affects care, health, and immunosuppression of these patients.

The limited role of myocardial fluorine-18 fluorodeoxyglucose imaging in candidates for cardiac transplantation: a planar imaging study.

This study compares the incidence and extent of hibernating myocardium (defined by myocardial perfusion/metabolism mismatch) in 28 cardiac transplant candidates with ischaemic cardiomyopathy and in 16 other patients with coronary artery disease (CAD) undergoing viability assessment. It then reviews the impact of myocardial perfusion metabolism imaging on management decisions in the transplant candidates at 6 months after scintigraphy. Each patient underwent a planar myocardial thallium-201 and fluorine-18 fluorodeoxyglucose scan on a modified gamma camera. Perfusion/metabolism mismatch was sized semi-quantitatively and each patient was assigned a global mismatch score. Transplant candidates had a lower left ventricular ejection fraction (LVEF) (P < 0.0002) and extent of hibernation myocardium (lower global mismatch score: P = 0.005) than other CAD patients but the difference in respect of mismatch frequency (8/28 vs 9/16 patients) did not reach statistical significance. Transplant candidates with LVEF < 20% had a lower global mismatch score (P < 0.02) than those with an LVEF > or = 20%. Interestingly two of three other CAD patients with LVEF < 20% had a moderate mismatch. Follow-up studies revealed the lack of impact of metabolic imaging as none of the three transplant candidates who eventually underwent revascularisation had hibernating myocardium and transplantation was offered to one of only two candidates with more than one minor mismatch. Thus metabolic imaging in potential transplant candidates may be of limited value because of the very low extent of hibernating myocardium, particularly if LVEF is below 20% and where clinical decisions are often based on many other factors.

Successful long-term outcome with prolonged ischemic time cardiac allografts.

BACKGROUND: The limited availability of cardiac allografts together with the increasing number of patients on the waiting list restricts treatment of this population with heart transplantation. An increase in the available donor pool has been facilitated by the use of allografts with prolonged ischemic time (> 240 minutes). METHODS: Short- and long-term outcomes were compared in 150 heart transplant recipients on the basis of allograft ischemic time (< 241 minutes, 241 to 300 minutes, and > 300 minutes). RESULTS: No difference was found in allograft functional capacity, the development of transplant-associated coronary disease, or actuarial survival in the short and long term. CONCLUSIONS: Improved population treatment with prolonged ischemic time cardiac allografts can be safely undertaken without long-term risk to heart transplant recipients.

Successful heart transplantation with cardiac allografts exposed to carbon monoxide poisoning.

The procurement of cardiac allografts from brain-dead donors who have suffered acute carbon monoxide poisoning has, in the past, been considered inadvisable. Two patients have recently undergone successful transplantation at our institution with cardiac allografts from donors who had suffered acute carbon monoxide poisoning. Carbon monoxide poisoning is not a contraindication to cardiac allograft procurement in the setting of clinical and objective evidence of satisfactory cardiac function.