Federico Pappalardo

Management of Ventricular Tachycardia in the Setting of a Dedicated Unit for the Treatment of Complex Ventricular Arrhythmias Long-Term Outcome After Ablation

Background— We investigated the impact of catheter ablation on ventricular tachycardia (VT) recurrence and survival in a large number of patients with structural heart disease treated in the setting of a dedicated multiskilled unit. Methods and Results— Since January 2007, we have implemented a multidisciplinary model, aiming for a comprehensive management of VT patients. Programmed ventricular stimulation was used to assess acute outcome. Primary end points were VT recurrence and the occurrence of cardiac and sudden cardiac death. Overall, 528 patients were treated by ablation (634 procedures; 1–4 procedures per patient). Among 482 tested with programmed ventricular stimulation after the last procedure, a class A result (noninducibility of any VT) was obtained in 371 patients (77%), class B (inducibility of nondocumented VT) in 12.4%, and class C (inducibility of index VT) in 10.6%. After a median follow-up time of 26 months, VT recurred in 164 (34.1%) of 472 patients. VT recurrence was documented in 28.6% of patients with a class A result versus 39.6% of patients with class B and 66.7% with class C result (log-rank P<0.001). The incidence of cardiac mortality was lower in class A patients than in those with class B and class C (8.4% versus 18.5% versus 22%, respectively; log-rank P=0.002). On the basis of multivariate analysis, postprocedural inducibility of index VT was independently associated both with VT recurrence (hazard ratio, 4.030; P<0.001) and with cardiac mortality (hazard ratio, 2.099; P=0.04). Conclusions— Within a dedicated VT unit, catheter ablation prevents long-term VT recurrences, which may favorably affect survival in a large number of patients who have VT.

Desmopressin reduces transfusion needs after surgery: a meta-analysis of randomized clinical trials.

Background:Perioperative pathologic microvascular bleeding is associated with increased morbidity and mortality and could be reduced by hemostatic drugs. At the same time, safety concerns regarding existing hemostatic agents include excess mortality. Numerous trials investigating desmopressin have lacked power to detect a beneficial effect on transfusion of blood products. The authors performed a meta-analysis of 38 randomized, placebo-controlled trials (2,488 patients) investigating desmopressin in surgery and indicating at least perioperative blood loss or transfusion of blood products. Methods:Pertinent studies were searched in BioMed Central, CENTRAL, and PubMed (updated May 1, 2008). Further hand or computerized searches involved recent (2003–2008) conference proceedings. Results:In most of the included studies, 0.3 &mgr;g/kg desmopressin was used prophylactically over a 15- to 30-min period. In comparison with placebo, desmopressin was associated with reduced requirements of blood product transfusion (standardized mean difference = −0.29 [−0.52 to −0.06] units per patient; P = 0.01), which were more pronounced in the subgroup of noncardiac surgery and were without a statistically significant increase in thromboembolic adverse events (57/1,002 = 5.7% in the desmopressin group vs. 45/979 = 4.6% in the placebo group; P = 0.3). Conclusions:Desmopressin slightly reduced blood loss (almost 80 ml per patient) and transfusion requirements (almost 0.3 units per patient) in surgical patients, without reduction in the proportion of patients who received transfusions. This meta-analysis suggests the importance of further large, randomized controlled studies using desmopressin in patients with or at risk of perioperative pathologic microvascular bleeding.

Extracorporeal membrane oxygenation (ECMO) in patients with H1N1 influenza infection: a systematic review and meta-analysis including 8 studies and 266 patients receiving ECMO

IntroductionH1N1 influenza can cause severe acute lung injury (ALI). Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients failing conventional mechanical ventilation, but its role is still controversial. We conducted a systematic review and meta-analysis on ECMO for H1N1-associated ALI.MethodsCENTRAL, Google Scholar, MEDLINE/PubMed and Scopus (updated 2 January 2012) were systematically searched. Studies reporting on 10 or more patients with H1N1 infection treated with ECMO were included. Baseline, procedural, outcome and validity data were systematically appraised and pooled, when appropriate, with random-effect methods.ResultsFrom 1,196 initial citations, 8 studies were selected, including 1,357 patients with confirmed/suspected H1N1 infection requiring intensive care unit admission, 266 (20%) of whom were treated with ECMO. Patients had a median Sequential Organ Failure Assessment (SOFA) score of 9, and had received mechanical ventilation before ECMO implementation for a median of two days. ECMO was implanted before inter-hospital patient transfer in 72% of cases and in most patients (94%) the veno-venous configuration was used. ECMO was maintained for a median of 10 days. Outcomes were highly variable among the included studies, with in-hospital or short-term mortality ranging between 8% and 65%, mainly depending on baseline patient features. Random-effect pooled estimates suggested an overall in-hospital mortality of 28% (95% confidence interval 18% to 37%; I2 = 64%).ConclusionsECMO is feasible and effective in patients with ALI due to H1N1 infection. Despite this, prolonged support (more than one week) is required in most cases, and subjects with severe comorbidities or multiorgan failure remain at high risk of in-hospital death.

Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial

IMPORTANCE No effective pharmaceutical agents have yet been identified to treat acute kidney injury after cardiac surgery. OBJECTIVE To determine whether fenoldopam reduces the need for renal replacement therapy in critically ill cardiac surgery patients with acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-blind, placebo-controlled, parallel-group study from March 2008 to April 2013 in 19 cardiovascular intensive care units in Italy. We randomly assigned 667 patients admitted to intensive care units after cardiac surgery with early acute kidney injury (≥50% increase of serum creatinine level from baseline or oliguria for ≥6 hours) to receive fenoldopam (338 patients) or placebo (329 patients). We used a computer-generated permuted block randomization sequence for treatment allocation. All patients completed their follow-up 30 days after surgery, and data were analyzed according to the intention-to-treat principle. INTERVENTIONS Continuous infusion of fenoldopam or placebo for up to 4 days with a starting dose of 0.1 μg/kg/min (range, 0.025-0.3 µg/kg/min). MAIN OUTCOMES AND MEASURES The primary end point was the rate of renal replacement therapy. Secondary end points included mortality (intensive care unit and 30-day mortality) and the rate of hypotension during study drug infusion. RESULTS The study was stopped for futility as recommended by the safety committee after a planned interim analysis. Sixty-nine of 338 patients (20%) allocated to the fenoldopam group and 60 of 329 patients (18%) allocated to the placebo group received renal replacement therapy (P = .47). Mortality at 30 days was 78 of 338 (23%) in the fenoldopam group and 74 of 329 (22%) in the placebo group (P = .86). Hypotension occurred in 85 (26%) patients in the fenoldopam group and in 49 (15%) patients in the placebo group (P = .001). CONCLUSIONS AND RELEVANCE Among patients with acute kidney injury after cardiac surgery, fenoldopam infusion, compared with placebo, did not reduce the need for renal replacement therapy or risk of 30-day mortality but was associated with an increased rate of hypotension. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00621790.

Miniaturized cardiopulmonary bypass improves short-term outcome in cardiac surgery: a meta-analysis of randomized controlled studies

OBJECTIVE To investigate whether the use of miniaturized cardiopulmonary bypass translates into decreased morbidity and mortality in patients having cardiac surgery. METHODS We independently conducted a systematic review and meta-analysis of data pooled from existing trials listed in PubMed and conference proceedings. Sixteen studies were identified, including 1619 patients having cardiac surgery. Inclusion criteria were random allocation to treatment and comparison of a miniaturized cardiopulmonary bypass system versus conventional cardiac surgery. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no outcome data. The end points were the rate of neurologic and myocardial damage and the number of patients transfused. RESULTS Miniaturized cardiopulmonary bypass was associated with significant reductions of neurologic damage (4/548 [0.7%] vs 19/555 [3.4%], odds ratio = 0.30 [0.12-0.73], P = .008), reduction in peak cardiac troponin (weighted mean difference = -0.15 ng/dL [-0.18, -0.11], P < .001), and in the number of transfused patients (55/552 [9.9%] vs 101/563 [17.9%], odds ratio = 0.42 [0.28-0.63], P < .001). No difference in mortality was noted (8/758 [1.0%] vs 14/771 [1.8%], odds ratio = 0.60 [0.26-1.39]). CONCLUSIONS Miniaturized cardiopulmonary bypass has beneficial effects resulting in decreased transfusion rate and cardiac and neurologic damage.

Levosimendan for Hemodynamic Support after Cardiac Surgery

BACKGROUND Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta‐analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS We conducted a multicenter, randomized, double‐blind, placebo‐controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30‐day mortality. RESULTS The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30‐day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], ‐5.7 to 5.9; P=0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, ‐2 hours; 95% CI, ‐5 to 1; P=0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, ‐12 hours; 95% CI, ‐21 to 2; P=0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, ‐1 to 2; P=0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS In patients who required perioperative hemodynamic support after cardiac surgery, low‐dose levosimendan in addition to standard care did not result in lower 30‐day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825.)

Concomitant implantation of Impella® on top of veno‐arterial extracorporeal membrane oxygenation may improve survival of patients with cardiogenic shock

Veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) support stabilizes patients with cardiogenic shock. Despite improved oxygenation and peripheral circulation, LV unloading may be impeded due to the increased afterload, resulting in a failing static left ventricle and in high mortality.

Recombinant Activated Factor VII in Cardiac Surgery: A Meta-analysis

OBJECTIVE Perioperative microvascular bleeding is associated with increased morbidity and mortality and could be reduced by hemostatic drugs such as recombinant activated factor VII (rFVIIa). Few trials have investigated rFVIIa and each individually lacked power to detect a beneficial effect on transfusion of blood products or thromboembolic side effects. DESIGN Meta-analysis. SETTING Hospitals. PARTICIPANTS The authors performed a meta-analysis of 5 clinical trials (1 randomized, 3 propensity matched, and 1 case matched) that included 298 patients and indicated major clinical outcome (survival and thromboembolic events). INTERVENTIONS Four of the 5 studies used rFVII in refractory blood loss. Doses varied between 17 and 70 microg/kg (repeatable) and 90 microg/kg for a single dose. MEASUREMENTS AND MAIN RESULTS The authors observed a nonsignificant reduction in the rate of surgical re-exploration (10/76 [13%] in the rFVIIa group v 42/74 [57%] in the control group, odds ratio [OR] = 0.25 [0.01-7.01], p for effect = 0.42), with a trend toward an increase in the rate of perioperative stroke (8/150 [5%] in the rFVIIa v 2/148 [1.4%] in the control arm, OR = 3.17 [0.83-12.10], p = 0.09) and no effect on mortality that was similar in the 2 groups (22/150 [15%] in the rFVIIa group and 22/148 [15%] in the control group [OR = 0.96 (0.50-1.86), p for effect=0.90]). CONCLUSIONS This analysis suggests that the hemostatic properties of rFVIIa could reduce the rate of surgical reexploration after cardiac surgery even if an increase of hazardous side effects (eg, perioperative stroke) could not be excluded. Because meta-analyses are hypothesis generating, this issue should be investigated further in large randomized controlled trials.

Bivalirudin Versus Heparin as an Anticoagulant During Extracorporeal Membrane Oxygenation: A Case-Control Study

OBJECTIVE Heparin-based anticoagulation for patients undergoing extracorporeal membrane oxygenation has many limitations, including a high risk of heparin-induced thrombocytopenia. However, little experience with other anticoagulants in these patients has been described. The aim of this study was to compare bivalirudin-based anticoagulation with heparin-based protocols in a population of patients treated with venovenous or venoarterial extracorporeal membrane oxygenation. DESIGN In this case-control study, 10 patients received bivalirudin (cases) and 10 heparin (controls). The target activated partial thromboplastin time (aPTT) was 45 to 60 seconds. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS aPTT variations >20% of the previous value were much more frequent in patients treated with heparin than in patients receiving bivalirudin (52 v 24, p < 0.001). The number of corrections of the anticoagulant dose was higher in the heparin group compared with the bivalirudin group (58 v 51), although it did not reach statistical significance. Bleeding, thromboembolic complications, extracorporeal membrane oxygenation (ECMO) support duration, mortality, and the number of episodes of aPTT >80 seconds were not different between the 2 groups. A further analysis was performed in the bivalirudin group according to the presence of acute renal failure requiring continuous venovenous hemofiltration. The median bivalirudin dose in patients with or without hemofiltration was 0.041 (0.028-0.05) mg/kg/h and 0.028 (0-0.041) mg/kg/h, respectively (p = 0.2). CONCLUSIONS Bivalirudin-based anticoagulation may represent a new method of anticoagulation for reducing thromboembolic and bleeding complications, which still jeopardize the application of extracorporeal membrane oxygenation. Moreover, bivalirudin is free from the risk of heparin-induced thrombocytopenia. Higher doses of bivalirudin may be needed in patients undergoing hemofiltration.

Recombinant Activated Factor VII Increases Stroke in Cardiac Surgery: A Meta-analysis

OBJECTIVES Recombinant activated factor VII (rFVIIa) is used in various surgical procedures to reduce the incidence of major blood loss and the need for re-exploration. Few clinical trials have investigated rFVIIa in cardiac surgery. The authors performed a meta-analysis focusing on the rate of stroke and surgical re-exploration. DESIGN Meta-analysis. SETTING Hospitals. PARTICIPANTS A total of 470 patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Four investigators independently searched PubMed and conference proceedings including backward snowballing (ie, scanning of reference of retrieved articles and pertinent reviews) and contacted international experts. A total of 470 patients (254 receiving rFVIIa and 216 controls) from 6 clinical trials (2 randomized, 3 propensity matched, and 1 case matched) were included in the analysis. The use of rFVIIa was associated with an increased rate of stroke (12/254 [4.7%] in the rFVIIa group v 2/216 [0.9%] in the control arm, odds ratio [OR] = 3.69 [1.1-12.38], p = 0.03) with a nonsignificant reduction in rate of surgical re-exploration (13% v 42% [OR = 0.27 (0.04-1.9), p = 0.19]). The authors observed a trend toward an increase of overall perioperative thromboembolic events (19/254 [7.5%] in the rFVIIa group v 10/216 [5.6%] in the control arm [OR = 1.84 (0.82-4.09), p = 0.14]). No difference in the rate of death was observed. CONCLUSIONS The administration of rFVIIa in cardiac surgery patients could result in a significant increase of stroke with a trend toward a reduction of the need for surgical re-exploration. The authors do not recommend routine use in cardiac surgery patients. rFVIIa may be considered with caution in patients with refractory life-threatening bleeding.