Effect of iloprost inhalation on postoperative outcome in high-risk cardiac surgical patients: a prospective randomized-controlled multicentre trial (ILOCARD).

PURPOSE: Perioperative right ventricular (RV) failure due to pressure overload from pulmonary hypertension (PH) worsens postoperative outcomes after cardiac surgery. Inhaled iloprost is a potent pulmonary vasodilator improving RV performance, ameliorating myocardial and pulmonary ischemia-reperfusion injury and attenuating inflammation. We hypothesized that the prophylactic inhalation of iloprost would reduce postoperative ventilation times after cardiac surgery. METHODS: In this phase III, multicentre, randomized, double-blind, placebo-controlled trial, we randomly assigned 253 cardiac surgical patients at high risk of perioperative RV failure to the prophylactic inhalation of 20 µg iloprost or placebo before and during weaning from extracorporeal circulation. The primary endpoint was the duration of postoperative ventilation. Secondary endpoints included perioperative hemodynamics, intensive care unit and hospital length of stay, and 90-day mortality. Safety was assessed by the incidence of adverse events. RESULTS: Iloprost had no significant effect on the median [interquartile range] duration of postoperative ventilation compared with placebo (720 [470-1170] min vs 778 [541-1219] min, respectively; median decrease, 65 min; 95% confidence interval [CI], - 77 to 210; P = 0.37). While the nebulization of iloprost decreased RV afterload and improved cardiac index, major secondary endpoints were not significantly affected. Ninety-day mortality occurred in 14% of the iloprost patients compared with 14% of the placebo patients (hazard ratio, 0.97; 95% CI, 0.50 to 1.89; P = 0.93). The incidence of adverse events was comparable in both groups. CONCLUSIONS: The prophylactic inhalation of iloprost did not meaningfully improve the outcome in high-risk cardiac surgical patients. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT00927654); registered 25 June, 2009.

RéSUMé: OBJECTIF: L'insuffisance cardiaque droite périopératoire due à une surcharge de pression provoquée par l'hypertension pulmonaire (HP) a un impact négatif sur le pronostic postopératoire après une chirurgie cardiaque. L'iloprost administré par inhalation est un vasodilatateur pulmonaire puissant qui améliore la performance du ventricule droit (VD), réduisant ainsi la lésion d'ischémie-reperfusion myocardique et pulmonaire et atténuant l'inflammation. Nous avons émis l'hypothèse qu'une inhalation prophylactique d'iloprost réduirait les temps de ventilation postopératoire après une chirurgie cardiaque. MéTHODE: Dans cette étude multicentrique de phase III, contrôlée par placebo, à double insu et randomisée, nous avons distribué aléatoirement 253 patients chirurgicaux courant un risque élevé d'insuffisance cardiaque droite périopératoire à une prophylaxie de 20 µg d'iloprost ou d'un placebo par inhalation avant et pendant le sevrage de la circulation extracorporelle. Le critère d'évaluation principal était la durée de ventilation postopératoire. Les critères d'évaluation secondaires étaient les données hémodynamiques périopératoires, la durée de séjour à l'unité de soins intensifs et à l'hôpital, et la mortalité à 90 jours. L'innocuité a été évaluée en fonction de l'incidence d'événements indésirables. RéSULTATS: L'iloprost n'a pas eu d'effet significatif sur la durée médiane [écart interquartile] de ventilation postopératoire par rapport au placebo (720 [470­1170] min vs 778 [541­1219] min, respectivement; réduction médiane, 65 min; intervalle de confiance [IC] 95 %, − 77 à 210; P = 0,37). Bien que la nébulisation d'iloprost ait réduit la post-charge du VD et amélioré l'index cardiaque, cette manœuvre n'a pas eu d'impact significatif sur les critères d'évaluation secondaires majeurs. Une mortalité à 90 jours a été observée chez 14 % des patients ayant reçu de l'iloprost, comparativement à 14 % des patients ayant reçu un placebo (rapport de risque, 0,97; IC 95 %, 0,50 à 1,89; P = 0,93). L'incidence d'événements indésirables était comparable dans les deux groupes. CONCLUSION: L'inhalation prophylactique d'iloprost n'a pas amélioré le pronostic des patients de chirurgie cardiaque à haut risque. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT00927654); enregistrée le 25 juin 2009.

Myocardial perfusion after one year of spinal cord stimulation in patients with refractory angina.

AIM: Spinal cord stimulation (SCS) is recommended for patients with coronary artery disease (CAD) and refractory angina. We used positron emission tomography (PET) to investigate the long-term effect of SCS on regional myocardial perfusion in patients suffering from angina pectoris refractory to medical treatment and without option for coronary intervention. PATIENTS, METHODS: We analyzed data of 44 patients with stable CAD (91% three vessel disease). At baseline, we determined coronary flow reserve (CFR) using 13N-ammonia-PET and myocardial viability with 18F-FDG. SCS was performed for one year (Medtronic Itrell III or Synergy, Düsseldorf, Germany). During follow-up, no cardiac interventions were necessary and no myocardial infarctions occurred. At one year follow-up, CFR was measured again. RESULTS: In the majority of patients (77%), SCS led to an improvement of clinical symptoms. CFR did not change significantly during follow-up. Subjective improvement did not correlate with an increase of CFR. CONCLUSIONS: Despite its clinical effect, SCS does not have a direct impact on CFR in patients with stable CAD. According to our results, the pain relief is not due to an improvement of the myocardial blood supply.

Myocardial sympathetic innervation in patients with symptomatic coronary artery disease: follow-up after 1 year with neurostimulation.

UNLABELLED: In both diabetic and nondiabetic patients, there is a loose correlation between coronary flow reserve (CFR) and sympathetic innervation in viable myocardial segments. The loose correlation implies that sympathetic innervation may be preserved even with major impairment of myocardial blood supply. In some patients, denervation is due to repetitive episodes of ischemia in areas with severely reduced CFR. We investigated the long-term effect of reduced CFR on myocardial sympathetic innervation in diabetic and nondiabetic patients with spinal cord stimulation. METHODS: We analyzed 23 patients (10 diabetic and 13 nondiabetic) with coronary artery disease and without known cardiac autonomic neuropathy. At baseline, we determined quantitative myocardial blood flow using (13)N-ammonia PET, myocardial viability using (18)F-FDG PET, and cardiac innervation using (11)C-hydroxyephedrine (HED) PET. At the 1-y follow-up we measured CFR and (11)C-HED retention. During follow-up, no cardiac intervention was performed and no myocardial infarction occurred. In all patients, spinal cord stimulation was performed for relief of angina. RESULTS: There was no significant difference in segmental (11)C-HED retention between baseline and follow-up in the whole patient group. In diabetic patients, as well as in segments with severely reduced CFR (<1.5), (11)C-HED retention showed a small but significant decrease (P<0.05). Linear regression of segmental (11)C-HED retention between baseline and follow-up was high (r(2)=0.81), confirming good reproducibility of the investigation on the one hand and little change in regional sympathetic innervation on the other hand. CONCLUSION: In patients with stable chronic coronary artery disease, sympathetic innervation of the myocardium is almost unchanged in both diabetic and nondiabetic patients in a 1-y follow-up. In myocardial segments with severely altered blood supply, a small but significant decrease in (11)C-HED retention most probably reflects ischemic neuronal damage. The prognostic relevance of sympathetic denervation in viable myocardium still has to be determined.

Cardiovascular magnetic resonance imaging for intensive care infants: safe and effective?

BACKGROUND: Cardiac magnetic resonance imaging (MRI) is an important diagnostic tool for congenital heart disease (CHD), as reflected by class 1 recommendations for the use of cardiac MRI by various consensus panels. However, little is known about the safety and clinical utility of cardiac MRI for these critically ill infants with CHD, whose further management cannot be directed by echocardiography. This study aimed to assess the safety, the potential hemodynamic side effects, and the clinical benefits of cardiac MRI for infants with complex CHD during their intensive care unit stay. METHODS: Infants referred from the pediatric cardiac intensive care unit (PCICU) to the authors' cardiac MRI program in the past 2 years were retrospectively analyzed using the electronic chart system available at their institution. Data collected included age, diagnosis, inotropic support, urine output, diuretic medication, body temperature and lactate levels, length of MRI examination, adverse effects during and after the procedure, clinical implications of MRI, length of stay in the PCICU, and mean blood pressure and heart rate before, during, and after MRI. RESULTS: Among 592 patients in the past 2 years, 20 (3.4%) were referred for MRI testing during their stay in the PCICU. The mean age of the infants was 4.8+/-3.2 months. Four of the patients were neonates, and eight were postoperative patients. Intracardiac malformations were present in 16 of the infants, vascular rings causing tracheal stenosis in 3 patients, and cardiomyopathy in 1 patient. The mean stay in the PCICU was 28+/-43 days. Eight of the infants were ventilated, with a mean fraction of inspired oxygen (FiO2) of 0.30+/-0.15. Four were receiving inotropic support. All the nonventilated children were intubated for the MRI and extubated in the MRI laboratory. The mean duration of the MRI (door-to-door time) was 110+/-27 min. All except one patient were hemodynamically stable, and no increase in catecholamine support was necessary during or after the scans. A 10-month-old girl receiving inotropic support needed a single dose of epinephrine due to a short episode of bradycardia after a breathhold for a contrast agent MRI angiography. Mean body core temperature at arrival to the PCICU was 36.8+/-0.7 degrees C. The mean serum lactate level after the MRI was 1.2+/-0.4 mmol/l. The mean blood pressure and heart rate before, during, and after MRI were unchanged. The mean diuresis on examination day was insignificantly lower (2.4%) than the day before with unchanged medication (5.09+/-1.58 vs 5.53+/-1.77 ml/kg/h). For 14 (70%) of the 20 patients, surgical or catheter interventional procedures were initiated based on novel MRI information. CONCLUSION: Cardiac MRI can be performed safely with low risk and limited hemodynamic changes for infants during their stay in the PCICU. Cardiac MRI provides key information for invasive management decisions in this subset of patients.