Intravenous ivabradine versus placebo in patients with low cardiac output syndrome treated by dobutamine after elective coronary artery bypass surgery: a phase 2 exploratory randomized controlled trial.

BACKGROUND: Low cardiac output syndrome (LCOS) is a severe condition which can occur after cardiac surgery, especially among patients with pre-existing left ventricular dysfunction. Dobutamine, its first-line treatment, is associated with sinus tachycardia. This study aims to assess the ability of intravenous ivabradine to decrease sinus tachycardia associated with dobutamine infused for LCOS after coronary artery bypass graft (CABG) surgery. METHODS: In a phase 2, multi-center, single-blind, randomized controlled trial, patients with left ventricular ejection fraction below 40% presenting sinus tachycardia of at least 100 beats per minute (bpm) following dobutamine infusion for LCOS after CABG surgery received either intravenous ivabradine or placebo (three ivabradine for one placebo). Treatment lasted until dobutamine weaning or up to 48 h. The primary endpoint was the proportion of patients achieving a heart rate (HR) in the 80- to 90-bpm range. Secondary endpoints were invasive and non-invasive hemodynamic parameters and arrhythmia events. RESULTS: Nineteen patients were included. More patients reached the primary endpoint in the ivabradine than in the placebo group (13 (93%) versus 2 (40%); P = 0.04). Median times to reach target HR were 1.0 h in the ivabradine group and 5.7 h in the placebo group. Ivabradine decreased HR (112 to 86 bpm, P <0.001) while increasing cardiac index (P = 0.02), stroke volume (P <0.001), and systolic blood pressure (P = 0.03). In the placebo group, these parameters remained unchanged from baseline. In the ivabradine group, five patients (36%) developed atrial fibrillation (AF) and one (7%) was discontinued for sustained AF; two (14%) were discontinued for bradycardia. CONCLUSION: Intravenous ivabradine achieved effective and rapid correction of sinus tachycardia in patients who received dobutamine for LCOS after CABG surgery. Simultaneously, stroke volume and systolic blood pressure increased, suggesting a beneficial effect of this treatment on tissue perfusion. TRIAL REGISTRATION: European Clinical Trials Database: EudraCT 2009-018175-14 . Registered February 2, 2010.

Circulatory Flow Restoration Versus Cardiopulmonary Resuscitation: New Therapeutic Approach in Sudden Cardiac Arrest.

Sudden cardiac arrest (SCA) remains a major problem for health authorities worldwide. Insufficiencies of current cardiopulmonary resuscitation (CPR) are most probably related to an inappropriate concept and applied methods that still concentrate on heartbeat as priority, instead of blood circulation to maintain organs' perfusions. The aim of this works is to propose a new therapeutic approach for SCA in a more effective and secure manner compared with current CPR methods. It correlates to a non-invasive circulatory flow restoration (CFR) device composed of a multilayered thoracic and infradiaphragmatic compartments that will be pulsated alternatively and in fixed frequencies using a low-pressure pneumatic generator. Proof-of-concept studies with different prototypes and methods of SCA, showed restoration of hemodynamics (BP ≥ 100 mm Hg) and increased urine output after 20 min of cardiac arrest in pediatric dogs and piglets. In summary, a CFR device can induce shear stress-mediated endothelial function to restore microcirculation and cellular metabolism. This represents a cost-effective method, predisposes to return of spontaneous circulation in case of SCA, adaptable for all age groups, in public and hospital environments.

Intrapulmonary shear stress enhancement: a new therapeutic approach in pulmonary arterial hypertension.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a dysfunctional endothelium disease with increased pulmonary vascular resistance (PVR) and poor prognosis. Current therapies are still insufficient. Here we propose a new pulsatile device as a more effective tool for PAH management compared with traditional treatments. MATERIALS AND METHODS: Twelve piglets (10.3 ± 3.8 kg) were given either intrapulmonary pulsatile [P (n = 6)] or nonpulsatile [NP (n = 6)] tadalafil treatment. After median sternotomy and heparin injection (250 IU/kg), both groups underwent aorto-pulmonary surgical shunt for 1 h. During a second 1 h period in group P, a catheter prototype, driven by a small ventilator, was introduced into the pulmonary trunk and pulsated intermittently at 110 bpm irrespective of heart rate (90.6 ± 10.74 bpm). In group NP, tadalafil was given orally (1 mg/kg). RESULTS: Hemodynamics and cardiac output (CO) were significantly (p < 0.05) improved in group P compared with group NP: CO was 0.56 ± 0.0.26 versus 0.54 ± 0.11 (L/min), respectively. Mean pulmonary artery pressure (PAP) was decreased in group P compared with group NP: PAP was 9.6 ± 2.97 versus 32.2 ± 5.07, respectively. Vascular resistances (dynes.s.cm(-5)/kg) were significantly lower in group P versus group NP: pulmonary resistance was 85 ± 42.12 versus 478 ± 192.91 and systemic resistance was 298.8 ± 172.85 versus 1301 ± 615.79, respectively. Using Western blot analysis, endogenous NO synthase expression in PA segments was nonsignificantly (p > 0.05) greater in group P (0.81 ± 0.78) versus (0.62 ± 0.35) group NP. CONCLUSION: Induced with an appropriate device, intrapulmonary shear stress-mediated endothelial function enhancement provides a more effective nearly physiological therapy for PAH.

Interruption of patent ductus arteriosus in children: robotically assisted versus videothoracoscopic surgery.

OBJECTIVES: If robotic surgery is to be widely used, the risks must be equivalent to those of standard techniques. This study analyzes the feasibility, safety, and efficiency of a robotically assisted technique for patent ductus arteriosus closure and compares the results with those of the videothoracoscopic technique. METHODS: During 2000, 56 children weighing 2.3 to 57 kg (mean, 12 kg) underwent surgical closure of a patent ductus arteriosus. They were distributed into 2 groups: 28 patients (group 1) underwent the videothoracoscopic technique, and 28 (group 2) underwent a robotically assisted (Zeus; Computer Motion, Inc, Goleta, Calif) approach. Operative and postoperative surgical data were studied. RESULTS: Operative time was significantly higher in the robotically assisted group. One conversion in videothoracoscopy was necessary, but no thoracotomy was required. Three persistent shunts were detected at postoperative echocardiography and were treated by means of application of a new clip with videothoracoscopy (1 in group 1 and 2 in group 2). No permanent laryngeal nerve injury and no hemorrhage were noted. The mean hospital stay was 3 days in both groups. CONCLUSIONS: Robotically assisted closure of a patent ductus arteriosus is comparable with closure by means of the videothoracoscopic technique. However, it requires a longer operative time because of the increment in complexity.

Shear stress, energy losses, and costs: a resolved dilemma of pulsatile cardiac assist devices.

Cardiac assist devices (CAD) cause endothelial dysfunction with considerable morbidity. Employment of pulsatile CAD remains controversial due to inadequate perfusion curves and costs. Alternatively, we are proposing a new concept of pulsatile CAD based on a fundamental revision of the entire circulatory system in correspondence with the physiopathology and law of physics. It concerns a double lumen disposable tube device that could be adapted to conventional cardiopulmonary bypass (CPB) and/or CAD, for inducing a homogenous, downstream pulsatile perfusion mode with lower energy losses. In this study, the device's prototypes were tested in a simulated conventional pediatric CPB circuit for energy losses and as a left ventricular assist device (LVAD) in ischemic piglets model for endothelial shear stress (ESS) evaluations. In conclusion and according to the study results the pulsatile tube was successfully capable of transforming a conventional CPB and/or CAD steady flow into a pulsatile perfusion mode, with nearly physiologic pulse pressure and lower energy losses. This represents a cost-effective promising method with low mortality and morbidity, especially in fragile cardiac patients.

Pulmonary artery dissection and rupture associated with aortopulmonary window.

A 31-year-old man with uncorrected aortopulmonary window and fixed pulmonary hypertension experienced dissection of the pulmonary artery, rapidly complicated by a fatal spontaneous rupture into the pericardium. In the setting of pulmonary hypertension, the diagnosis of dissection and rupture of the pulmonary artery should be considered in cases of thoracic pain or cardiogenic shock.