Gilbert Kirkorian

Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction

BACKGROUND Experimental evidence suggests that cyclosporine, which inhibits the opening of mitochondrial permeability-transition pores, attenuates lethal myocardial injury that occurs at the time of reperfusion. In this pilot trial, we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct during acute myocardial infarction. METHODS We randomly assigned 58 patients who presented with acute ST-elevation myocardial infarction to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight (cyclosporine group) or normal saline (control group) immediately before undergoing PCI. Infarct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging (MRI) on day 5 after infarction. RESULTS The cyclosporine and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before PCI. The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group (P=0.04). The release of troponin I was not significantly reduced (P=0.15). On day 5, the absolute mass of the area of hyperenhancement (i.e., infarcted tissue) on MRI was significantly reduced in the cyclosporine group as compared with the control group, with a median of 37 g (interquartile range, 21 to 51) versus 46 g (interquartile range, 20 to 65; P=0.04). No adverse effects of cyclosporine administration were detected. CONCLUSIONS In our small, pilot trial, administration of cyclosporine at the time of reperfusion was associated with a smaller infarct by some measures than that seen with placebo. These data are preliminary and require confirmation in a larger clinical trial.

Long-Term Benefit of Postconditioning

Background— We previously demonstrated that ischemic postconditioning decreases creatine kinase release, a surrogate marker for infarct size, in patients with acute myocardial infarction. Our objective was to determine whether ischemic postconditioning could afford (1) a persistent infarct size limitation and (2) an improved recovery of myocardial contractile function several months after infarction. Methods and Results— Patients presenting within 6 hours of the onset of chest pain, with suspicion for a first ST-segment–elevation myocardial infarction, and for whom the clinical decision was made to treat with percutaneous coronary intervention, were eligible for enrollment. After reperfusion by direct stenting, 38 patients were randomly assigned to a control (no intervention; n=21) or postconditioned group (repeated inflation and deflation of the angioplasty balloon; n=17). Infarct size was assessed both by cardiac enzyme release during early reperfusion and by 201thallium single photon emission computed tomography at 6 months after acute myocardial infarction. At 1 year, global and regional contractile function was evaluated by echocardiography. At 6 months after acute myocardial infarction, single photon emission computed tomography rest-redistribution index (a surrogate for infarct size) averaged 11.8±10.3% versus 19.5±13.3% in the postconditioned versus control group (P=0.04), in agreement with the significant reduction in creatine kinase and troponin I release observed in the postconditioned versus control group (−40% and −47%, respectively). At 1 year, the postconditioned group exhibited a 7% increase in left ventricular ejection fraction compared with control (P=0.04). Conclusions— Postconditioning affords persistent infarct size reduction and improves long-term functional recovery in patients with acute myocardial infarction.

Comparison of Thrombolysis Followed by Broad Use of Percutaneous Coronary Intervention With Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Acute Myocardial Infarction : Data From the French Registry on Acute ST-Elevation Myocardial Infarction (FAST-MI)

Background— Intravenous thrombolysis remains a widely used treatment for ST-elevation myocardial infarction; however, it carries a higher risk of reinfarction than primary PCI (PPCI). There are few data comparing PPCI with thrombolysis followed by routine angiography and PCI. The purpose of the present study was to assess contemporary outcomes in ST-elevation myocardial infarction patients, with specific emphasis on comparing a pharmacoinvasive strategy (thrombolysis followed by routine angiography) with PPCI. Methods and Results— This nationwide registry in France included 223 centers and 1714 patients over a 1-month period at the end of 2005, with 1-year follow-up. Sixty percent of the patients underwent reperfusion therapy, 33% with PPCI and 29% with intravenous thrombolysis (18% prehospital). At baseline, the Global Registry of Acute Coronary Events score was similar in thrombolysis and PPCI patients. Time to initiation of reperfusion therapy was significantly shorter in thrombolysis than in PPCI (median 130 versus 300 minutes). After thrombolysis, 96% of patients had coronary angiography, and 84% had subsequent PCI (58% within 24 hours). In-hospital mortality was 4.3% for thrombolysis and 5.0% for PPCI. In patients with thrombolysis, 30-day mortality was 9.2% when PCI was not used and 3.9% when PCI was subsequently performed (4.0% if PCI was performed in the same hospital and 3.3% if performed after transfer to another facility). One-year survival was 94% for thrombolysis and 92% for PPCI (P=0.31). After propensity score matching, 1-year survival was 94% and 93%, respectively. Conclusions— When used early after the onset of symptoms, a pharmacoinvasive strategy that combines thrombolysis with a liberal use of PCI yields early and 1-year survival rates that are comparable to those of PPCI.

Antibiotic Prophylaxis for Permanent Pacemaker Implantation A Meta-Analysis

BACKGROUND Infection remains a serious complication after permanent pacemaker implantation. Antibiotic prophylaxis is frequently prescribed at the time of insertion to reduce its incidence, although results of well-designed, controlled studies are lacking. METHODS AND RESULTS We performed a meta-analysis of all available randomized trials to evaluate the effectiveness of antibiotic prophylaxis to reduce infection rates after permanent pacemaker implantation. Reports of trials were identified through a Medline, Embase, Current Contents, and an extensive bibliography search. Trials that met the following criteria were included: (1) prospective, randomized, controlled, open or blind trials; (2) patients assigned to a systemic antibiotic group or a control group; (3) end point events related to any infection after pacemaker implantation: wound infection, septicemia, pocket abscess, purulent secretion, right infective endocarditis, inflammatory signs, a positive culture, septic pulmonary embolism, or repeat operation for an infective complication. Seven trials met the inclusion criteria. They included 2023 patients with established permanent pacemaker implantation (new implants or replacements). The incidence of end point events in control groups ranged from 0% to 12%. The meta-analysis suggested a consistent protective effect of antibiotic pretreatment (P=.0046; common odds ratio: 0.256, 95% confidence interval: 0.10 to 0.656). CONCLUSIONS Results of the present meta-analysis suggest that systemic antibiotic prophylaxis significantly reduces the incidence of potentially serious infective complications after permanent pacemaker implantation. They support the use of prophylactic antibiotics at the time of pacemaker insertion to prevent short-term pocket infection, skin erosion or septicemia.

Radiofrequency ablation of atrial flutter. Efficacy of an anatomically guided approach.

BackgroundPrevious reports have shown that radiofrequency ablation can terminate atrial flutter and prevent recurrences. However, different methods have been used, and the current experience remains limited. The objective of the present study was to determine the efficacy of radiofrequency ablation of atrial tissue in patients with atrial flutter using an anatomically guided approach. Methods and ResultsWe treated 22 patients aged 30 to 73 years. Atrial flutter was recurrent for a mean of 5 years despite the administration of multiple antiarrhythmic drugs. Radiofrequency current was directed to the atrial isthmus between the inferior vena cava and the tricuspid ring, regardless of the morphology of local electrograms. Radiofrequency energy was applied during typical atrial flutter in 12 patients, atypical atrial flutter in 2 patients, and successively both forms in 8 patients. In 19 patients, atrial flutter abruptly terminated. In 3 patients, atrial flutter persisted despite 37, 48, and 25 applications, respectively. Atrial recordings demonstrated that atrial flutter termination occurred as a consequence of conduction block at the site of radiofrequency energy application, regardless of the type of atrial flutter. The number of applications before termination ranged from 1 to 82 (mean, 32). Atrial flutter could no longer be induced in every case. There were no complications. During a 13-month mean follow-up, atrial flutter recurred in only 2 of the 19 patients who had a successful ablation. Four patients experienced chronic atrial fibrillation, and 2 of them returned to sinus rhythm with antiarrhythmic therapy. ConclusionsRadiofrequency ablation of atrial flutter using anatomic guidance is feasible and effective. Further experience is needed to delineate its role as an alternative approach to the management of refractory atrial flutter.

Comparison of primary angioplasty and pre-hospital fibrinolysis in acute myocardial infarction (CAPTIM) trial: a 5-year follow-up

AIMS The CAPTIM (Comparison of primary Angioplasty and Pre-hospital fibrinolysis In acute Myocardial infarction) study found no evidence that a strategy of primary angioplasty was superior in terms of 30-day outcomes to a strategy of pre-hospital fibrinolysis with transfer to an interventional facility in patients managed early at the acute phase of an acute myocardial infarction. The present analysis was designed to compare both strategies at 5 years. METHODS AND RESULTS The CAPTIM study included 840 patients managed in a pre-hospital setting within 6 h of an acute ST-segment elevation myocardial infarction. Patients were randomized to either a primary angioplasty (n = 421) or a pre-hospital fibrinolysis (rt-PA) with immediate transfer to a centre with interventional facilities (n = 419). Long-term follow-up was obtained in blinded fashion from 795 patients (94.6%). Using an intent-to-treat analysis, all-cause mortality at 5 years was 9.7% in the pre-hospital fibrinolysis group when compared with 12.6% in the primary angioplasty group [HR 0.75 (95% CI, 0.50-1.14); P = 0.18]. For patients included within 2 h, 5 year mortality was 5.8% in the pre-hospital fibrinolysis group when compared with 11.1% in the primary angioplasty group [HR 0.50 (95% CI, 0.25-0.97); P = 0.04], whereas it was, respectively, 14.5 and 14.4% in patients included after 2 h [HR 1.02, (95% CI 0.59-1.75), P = 0.92]. CONCLUSION The 5-year follow-up is consistent with the 30-day outcomes of the trial, showing similar mortality for primary percutaneous coronary intervention and a policy of pre-hospital lysis followed by transfer to an interventional center. In addition, for patients treated within 2 h of symptom onset, 5-year mortality was lower with pre-hospital lysis.

Catheter ablation of the atrial myocardium in human type I atrial flutter.

To avoid atrioventricular node-His bundle ablation, catheter ablation of the atrial myocardium was attempted in eight patients with drug refractory type I atrial flutter. In seven of eight patients, a zone of prolongation and fragmentation of the endocardial electrogram was found in the low posterior part of the right atrium. Entrainment of the atrial flutter by high right atrial pacing was accompanied by local recording of second-degree regional block in several atrial sectors but never in the low septal area. We, therefore, hypothesized that the latter represented the critical slow conduction zone of the reentrant flutter circuit. One or two cathodal DC shocks were locally delivered without immediate or late complications. One single ablation attempt was performed in five patients, whereas three patients underwent a second attempt because of early flutter recurrence. Patients were initially discharged without (and after a second session with) antiarrhythmic drugs. After a mean follow-up of 15.5 months (range, 10-23 months), five patients are free of arrhythmias without antiarrhythmic drug therapy. Two patients did not experience atrial arrhythmias while on a drug regimen that was previously found to be ineffective, and a third patient had flutter recurrences. This study suggests that patients with type I atrial flutter referred for atrioventricular node-His bundle ablation may be successfully managed by delivering the ablative shock directly on the atrial arrhythmia substrate.

Improved prediction of awakening or nonawakening from severe anoxic coma using tree-based classification analysis.

Objective:To evaluate the utility of sensory and event-related evoked potentials for the prediction of awakening/nonawakening in severe anoxic coma and to design a decision tree helping decision for any patient in this condition. Design:Prospective cohort study. Setting:Clinical neurophysiology unit and intensive care unit of a French university hospital. Patients:Sixty-two consecutive severe comatose patients after out-of-hospital cardiac arrest. Interventions:None Measurements and Main Results:We gathered clinical variables and recorded the somatosensory, auditory, and cognitive evoked potentials within an average period of 8 days after cardiac arrest. The patients were followed for 12 months and classified as awake or nonawake (permanent vegetative state or death). The statistical study included measurements of specificity, sensitivity, and positive and negative predictive value for each clinical and electrophysiologic variable recorded at the early stage of coma. Furthermore, a tree-based classification analysis was performed. All patients in whom somatosensory evoked potentials or middle-latency auditory evoked potentials were abolished did not awaken (100% specificity). All patients in whom mismatch negativity (MMN) was present awakened (100% specificity). MMN was superior to somatosensory evoked potentials for the prediction of awakening and had the best specificity and positive predictive value for awakening. On the decision tree, the awakening/nonawakening explicative variables were, by order of importance, MMN, pupillary reactivity, and somatosensory evoked potentials. Conclusions:There is a need to predict early and accurately awakening or nonawakening in postanoxic comas. Using sensory and cognitive evoked potentials to assess the functional condition of the brain, a prognostic tree for the prediction of awakening/nonawakening in severe anoxic coma has been designed. It is applicable to any patient in this condition and offers the possibility to predict with very high probability awakening when MMN, the earliest component of event-related potentials, is present and nonawakening when MMN and pupillary light reflex are absent or cortical components of somatosensory evoked potentials are abolished.

Role of the Preaxillary Flora in Pacemaker Infections: A Prospective Study

BACKGROUND Infection remains a severe complication after pacemaker implantation. The purpose of our prospective study was to evaluate the role of the local bacteriologic flora in its occurrence. METHODS AND RESULTS Specimens were collected at the site of implantation for culture from the skin and the pocket before and after insertion in a consecutive series of patients who underwent elective permanent pacemaker implantation. Microorganisms isolated both at the time of insertion and of any potentially infective complication were compared by using conventional speciation and ribotyping. There were 103 patients (67 men and 36 women) whose age ranged from 16 to 93 years (mean+/-SD, 67+/-15). At the time of pacemaker implantation, a total of 267 isolates were identified. The majority (85%) were staphylococci. During a mean follow-up of 16.5 months (range, 1 to 24), infection occurred in four patients (3.9%). In two of them, an isolate of Staphylococcus schleiferi was recognized by molecular method as identical to the one previously found in the pacemaker pocket. In one patient, Staphylococcus aureus, an organism that was absent at the time of pacemaker insertion, was isolated. In another patient, a Staphylococcus epidermidis was identified both at the time of pacemaker insertion and when erosion occurred; however, their antibiotic resistance profiles were different. CONCLUSIONS This study strongly supports the hypothesis that pacemaker-related infections are mainly due to local contamination during implantation. S schleiferi appears to play an underestimated role in infectious colonization of implanted biomaterials and should be regarded as an important opportunistic pathogen.

Amiodarone versus placebo and class ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis

OBJECTIVES This meta-analysis compared amiodarone with placebo and class Ic drugs for the cardioversion of recent-onset atrial fibrillation (AF), defined as lasting less than seven days. BACKGROUND Despite the lack of trials that support its efficacy convincingly, amiodarone is widely used for conversion of recent-onset AF. METHODS We searched Medline and EMBASE databases, as well as the Cochrane Controlled Trials Register for randomized trials on recent-onset AF comparing amiodarone to placebo or class Ic drugs. Data were combined according to a fixed effect model. The primary end point was the rate of conversion at 24 h. To study time-dependency of the drugs, efficacy at 1 to 2 h, 3 to 5 h, 6 to 8 h, and at 24 h was analyzed. RESULTS We found six studies randomizing amiodarone versus placebo (595 patients) and seven studies versus class Ic drugs (579 patients). There was no significant difference between amiodarone and placebo at 1 to 2 h, but significant efficacy was found after 6 to 8 h (relative risk [RR] 1.23, p = 0.022) and at 24 h (RR 1.44, p < 0.001). Efficacy with amiodarone was inferior to class Ic drugs for up to 8 h (RR 0.67, p < 0.001) but no difference was seen at 24 h (RR 0.95, p = 0.50). There were no major adverse effects. CONCLUSIONS Amiodarone is superior to placebo for cardioversion of AF, and even though the onset of conversion is delayed, its efficacy is similar at 24 h compared with class Ic drugs. These results favor amiodarone as a reasonable alternative for patients with recent AF in whom class Ic and other, more rapidly acting antiarrhythmic drugs cannot be used.