Management of the sensitized cardiac recipient: the use of plasmapheresis and intravenous immunoglobulin.

Previously, we reported that the combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIg) allow sensitized patients to undergo orthotopic heart transplantation (OHT), even across a positive crossmatch. In the current study, the effect of that combination, PP+IVIg, on survival of a larger group of such recipients is investigated. The latter group (I) consisted of 35 sensitized patients who received PP+IVIG together with standard immunosuppressive drugs. Rejection was seen in 11 patients, findings strongly suggestive of a vascular (humoral) being identified in five of those cases. Four deaths occurred, two of them in the immediate post-operative period, one after almost six months, and one after almost two yr post-OHT. Follow-up range 4.5 months to 7.8 yr post-OHT (average=1.1 yr). Patient survival was analyzed after generation of a Kaplan-Meier plot. Comparison with a control OHT group (II) given standard immunosuppressive drugs only (N=276) showed enhanced survival of group I (p=0.0414 by log-rank test). We conclude that the combination of PP and IVIG (i) is associated with declines in T- and B-percent-reactive antibody and in crossmatch positivity, and (ii) is very useful in the management of the sensitized cardiac patient undergoing OHT, often allowing a successful outcome to transplantation in the face of a positive crossmatch.

Mechanisms whereby rapid RV pacing causes LV dysfunction: perfusion-contraction matching and NO.

Incessant tachycardia induces dilated cardiomyopathy in humans and experimental models; mechanisms are incompletely understood. We hypothesized that excessive chronotropic demands require compensatory contractility reductions to balance metabolic requirements. We studied 24 conscious dogs during rapid right ventricular (RV) pacing over 4 wk. We measured hemodynamic, coronary blood flow (CBF), myocardial O(2) consumption (MVO(2)) responses, myocardial nitric oxide (NO) production, and substrate utilization. Early pacing (6 h) resulted in decreased heart rate (HR)-adjusted coronary blood flow (CBF), MVO(2) (CBF/beat: 0.33 +/- 0.02 to 0.19 +/- 0.01 ml, P < 0.001, MVO(2)/beat: 0.031 +/- 0.002 to 0.016 +/- 0.001 ml O(2), P < 0.001), and contractility [left ventricular (LV) first derivative pressure (dP/dt)/LV end-diastolic diameter (EDD): 65 +/- 4 to 44 +/- 3 mmHg x s(-1) x mm(-1), P < 0.01], consistent with flow-metabolism-function coupling, which persisted over the first 72 h of pacing (CBF/beat: 0.15 +/- 0.01 ml, MVO(2)/beat: 0.013 +/- 0.001 ml O(2), P < 0.001). Thereafter, CBF per beat and MVO(2) per beat increased (CBF/beat: 0.25 +/- 0.01 ml, MVO(2)/beat: 0.021 +/- 0.001 ml O(2) at 28 days, P < 0.01 vs. 72 h). Contractility declined [(LV dP/dt)/LVEDD: 19 +/- 2 mmHg x s(-1) x mm(-1), P < 0.0001], signifying flow-function mismatch. Cardiac NO production, endothelial NO synthase expression, and fatty acid utilization decreased in late phase, whereas glycogen content and lactate uptake increased. Incessant tachycardia induces contractile, metabolic, and flow abnormalities reflecting flow-function matching early, but progresses to LV dysfunction late, despite restoration of flow and metabolism. The shift to flow-function mismatch is associated with impaired myocardial NO production.

When cancer and heart failure cross paths: a case report of severe cardiorenal compromise associated with the anti-CD20 monoclonal antibody rituximab in a patient with dilated cardiomyopathy.

The authors describe the case of a 41-year-old man with end-stage, nonischemic dilated cardiomyopathy of 11 years' duration. The patient had been deemed ineligible for transplantation, despite his young age, when he was diagnosed with non-Hodgkin's lymphoma 7 years previously. Since he had survived the lymphoma without significant chemotherapy, while his cardiovascular and renal status continued to deteriorate, the issue was revisited. In an attempt to at least render him eligible for an assist device, a novel, promising, and reportedly nontoxic immunomodulation therapy for his lymphoma was employed. This consisted of infusion of the monoclonal antibody rituximab, specifically targeting the CD20 antigen on B cells. Despite testimonials concerning the benign nature of the treatment, the patient was unable to tolerate it and his clinical condition deteriorated rapidly, eventually leading to his death. The authors discuss potential mechanisms that might have accounted for the patient's cardiorenal compromise, with a focus on a very rare "cytokine release" syndrome attributed to this type of monoclonal antibody therapy and the probable interplay of cytokines in advanced heart failure. (c)2001 CHF, Inc.

Acute pancreatitis as the first manifestation of hyperparathyroidism in an otherwise asymptomatic patient.

Acute pancreatitis as a manifestation of hyperparathyroidism (HPT) has been reported in the literature but the concept of causal relationship has been disputed. We report a case of acute pancreatitis where the presence of hypercalcemia led to the diagnosis of primary HPT. No other current risk factors for pancreatitis were identified and no symptoms of HPT were present prior to this episode. We review the literature regarding the role of HPT in the pathogenesis of acute pancreatitis.