Outcome of out-of-hospital cardiac arrest after fibrinolysis with reteplase in comparison to the return of spontaneous circulation after cardiac arrest score in a geographic region without emergency coronary intervention.

Coronary occlusion and pulmonary embolism are responsible for the majority of cases of out-of-hospital cardiac arrest (OHCA). Despite previous favourable results of pre-hospital fibrinolysis in cases of OHCA, the benefit could not be confirmed in a large controlled study using the fibrinolytic tenecteplase. For reteplase (r-PA), there are hardly any data regarding pre-hospital fibrinolysis during ongoing resuscitation. The present study reported results using r-PA therapy in a German physician-supported Emergency Medical Services system. The data of OHCA patients who received pre-hospital fibrinolytic treatment with r-PA after an individual risk/benefit assessment were retrospectively analysed. To assess the effectiveness of this approach, the rate of patients with a return of spontaneous circulation (ROSC) was compared with the corresponding figure that was calculated with the help of the RACA (ROSC after cardiac arrest) score. The RACA algorithm predicts the probability of ROSC based on data from the German Resuscitation Registry. Further outcome data comprised hospital discharge rate and neurologic status at discharge. From 2001 to 2009, 43 patients (mean age, 58.5 years; 65.1% male; 58.1% ventricular fibrillation) received r-PA. Of these, 20 patients (46.5%) achieved ROSC, compared to a probability of 49.8% according to the RACA score (P=0.58). A total of 8 patients (18.6%) were discharged alive, including 5 (11.2%) with a good neurological outcome. For the analysed small patient collective, pre-hospital r-PA did not offer any benefits with regard to the ROSC rate. Further analyses of larger patient numbers on a nationwide registry basis are recommended.

Prostaglandin E1 testing in heart failure-associated pulmonary hypertension enables transplantation: the PROPHET study.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) is relevant to prognosis of congestive heart failure and heart transplantation. Proof of reversibility by pharmacologic testing in potential transplantation candidates is important because it indicates a reduced probability of right ventricular failure or death in the early post-transplant period. This study aimed to clarify the possible extent of acute reversibility of elevated PVR in a large, consecutive cohort of heart transplant candidates. METHODS: This study included 208 consecutive patients (age 52 +/- 10 years, 89% men and 11% women, ejection fraction 21 +/- 9%, Vo2max 12.6 +/- 4.2 ml/kg/min) being evaluated for heart transplantation in 7 transplant centers in Germany and Switzerland. Testing was performed with increasing intravenous doses of prostaglandin E1 (PGE1; average maximum dose 173 +/- 115 ng/kg/min for at least 10 minutes) in 92 patients exhibiting a baseline PVR of > 2.5 Wood units (WU) and/or a transpulmonary gradient (TPG) of > 12 mm Hg. RESULTS: PGE1 testing lowered PVR from 4.1 +/- 2.0 to 2.1 +/- 1.1 WU (p < 0.01), increased cardiac output from 3.8 +/- 1.0 to 5.0 +/- 1.5 liters/min (p < 0.01), and decreased TPG from 14 +/- 4 to 10 +/- 3 mm Hg (p < 0.01), mean pulmonary artery pressure (PAM) from 39 +/- 9 to 29 +/- 9 mm Hg (p < 0.01) and mean pulmonary capillary wedge pressure (PCWP) from 24 +/- 7 to 19 +/- 9 mm Hg (p < 0.01). Mean aortic pressure (MAP) decreased to 85% and systemic vascular resistance (SVR) to 65% of baseline values (p < 0.01). Symptomatic systemic hypotension was not observed. For the whole population the percentage of patients with PVR > 2.5 WU was reduced from 44.2% to 10.5% with PGE1. PVR decreased in each patient; only 2 patients (1%) remained ineligible for listing because of a final PVR of > 4.0 WU. TPG, ejection fraction and male gender were independent predictors of reversibility of PVR. CONCLUSIONS: Elevated PVR in heart transplant candidates is highly reversible and can be normalized during acute pharmacologic testing with PGE1.

Reduction of cyclosporine after introduction of mycophenolate mofetil improves chronic renal dysfunction in heart transplant recipients--the IMPROVED multi-centre study.

AIMS: This comparative prospective multi-centre study evaluated efficacy and safety of cyclosporine A downtitration in heart transplant recipients with chronic renal dysfunction potentially attributable to cyclosporine (n=161). METHODS: In the intervention arm (n=109, recruited from 9 centres), mycophenolate mofetil was introduced de novo or substituting azathioprine, followed by cyclosporine reduction (target trough levels 2-4 microg/ml and 50 ng/ml, respectively). In controls (n=52, recruited from 1 centre), immunosuppression remained unchanged. Renal function was recorded twelve, six, and three months before, and throughout the eight-month study period. RESULTS: At study entry, cyclosporine trough levels and renal function parameters were comparable. At study end, mean+/-SD cyclosporine in the intervention arm was 57+/-24 vs. 116+/-36 ng/ml in controls. During the study, creatinine decreased by 23.3+/-50.7 micromol/l (P<0.0001) in the intervention arm but increased by 7.3+/-46.9 micromol/l (P=0.992) in controls (P=0.0001 for comparison between groups). A creatinine reduction of at least 20% was found in 35% of subjects of the intervention arm but only in 4% in the control arm (P<0.0001 for comparison between groups). Improvement in renal function was not weakened after adjustment for baseline characteristics in multiple regression analysis. Renal function improved in strata of creatinine entry values from 150 to 310 micromol/l, regardless of the presence of diabetes. Myocardial biopsies at target levels for cyclosporine and mycophenolate mofetil showed three reversible subclinical rejection episodes. CONCLUSIONS: Cyclosporine downtitration improved renal dysfunction in diabetic and non-diabetic heart transplant recipients across a wide range of creatinine levels. The long-term benefit of this strategy deserves further study.