Christopher P. Lawrance

Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia.

Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P < 0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.

A minimally invasive Cox maze IV procedure is as effective as sternotomy while decreasing major morbidity and hospital stay.

OBJECTIVES The Cox maze IV procedure has the best results for the surgical treatment of atrial fibrillation. It has been traditionally performed through sternotomy with excellent outcomes, but this has been considered to be too invasive. An alternative approach is to perform a less invasive right anterolateral minithoracotomy. This series compared these approaches at a single center in consecutive patients. METHODS Patients undergoing a Cox maze IV procedure (n = 356) were retrospectively reviewed from January 2002 to February 2014. Patients were stratified into 2 groups: right minithoracotomy (RMT; n = 104) and sternotomy (ST; n = 252). Preoperative and perioperative variables were compared as well as long-term outcomes. Patients were followed up for 2 years and rhythm was confirmed with an electrocardiogram or prolonged monitoring. RESULTS Freedom from atrial tachyarrhythmias off antiarrhythmic drugs was 81% and 74% at 1 and 2 years, respectively, using an RMT approach and was not significantly different from the ST group at these same time points. The overall complication rate was lower in the RMT group (6% vs 13%, P = .044) as was 30-day morality (0% vs 4%, P = .039). Median length of stay in the intensive care unit was lower in the RMT group than in the ST group (2 days [range, 0-21 days] vs 3 days [range, 1-61 days]; P = .004) as was median hospital length of stay (7 days [range, 4-35 days] vs 9 days [range, 1-111 days]; P < .001). CONCLUSIONS The Cox maze IV procedure performed through a right minithoracotomy is as effective as sternotomy in the treatment of atrial fibrillation. This approach was associated with fewer complications, decreased mortality and decreased length of stay in the intensive care unit and hospital length of stay.

Comparison of the stand-alone Cox-Maze IV procedure to the concomitant Cox-Maze IV and mitral valve procedure for atrial fibrillation

BACKGROUND The majority of patients undergoing surgical ablation for atrial fibrillation (AF) worldwide receive a concomitant mitral valve (MV) procedure. This study compared outcomes of the Cox-Maze IV (CMIV) in patients with lone AF to those with AF and MV disease. METHODS A retrospective review of 335 patients receiving either a stand-alone CMIV for AF (n=151) or a CMIV with a MV procedure (n=184) was performed from January 2002 through December of 2012. Data were obtained at 3, 6, 12, 24, and 48 months and patients were evaluated for recurrence of AF. Twenty-four preoperative and perioperative variables were evaluated to identify predictors of AF recurrence at one year. RESULTS The two groups differed in that stand-alone CMIV patients were younger, had AF of longer duration and had more failed catheter ablations, while patients with AF and MV disease had larger left atria and worse New York Heart Association class (P≤0.001). Operative mortality was higher in the concomitant MV group (1% vs. 5%, P=0.015). Freedom from AF and antiarrhythmic drugs at 12 and 24 months were similar between the two groups (73% and 76% at 12 months; 77% vs. 78% at 24 months). Predictors of recurrence included failure to use a box-lesion to isolate the pulmonary veins and posterior left atria, early recurrence of atrial tachyarrhythmias (ATAs) and the presence of a preoperative pacemaker (P=0.001). CONCLUSIONS The efficacy of the CMIV procedure was similar in patients with and without co-existent MV pathology. Patients receiving a concomitant CMIV and MV procedure represented an older and sicker patient population and had higher mortality rates than those receiving a stand-alone CMIV procedure.

Detection of atrial fibrillation after surgical ablation: Conventional versus continuous monitoring

BACKGROUND Current guidelines recommend at least 24-hour Holter monitoring at 6-month intervals to evaluate the recurrence of atrial fibrillation (AF) after surgical ablation. In this prospective multicenter study, conventional intermittent methods of AF monitoring were compared with continuous monitoring using an implantable loop recorder (ILR). METHODS From August 2011 to January 2014, 47 patients receiving surgical treatment for AF at 2 institutions had an ILR placed at the time of operation. Each atrial tachyarrhythmia (ATA) of 2 minutes or more was saved. Patients transmitted ILR recordings bimonthly or after any symptomatic event. Up to 27 minutes of data was stored before files were overwritten. Patients also underwent electrocardiography (ECG) and 24-hour Holter monitoring at 3, 6, and 12 months. ILR compliance was defined as any transmission between 0 and 3 months, 3 and 6 months, or 6 and 12 months. Freedom from ATAs was calculated and compared. RESULTS ILR compliance at 12 months was 93% compared with ECG and Holter monitoring compliance of 85% and 76%, respectively. ILR devices reported a total of 20,878 ATAs. Of these, 11% of episodes were available for review and 46% were confirmed as AF. Freedom from ATAs was no different between continuous and intermittent monitoring at 1 year. Symptomatic events accounted for 187 episodes; however, only 10% were confirmed as AF. CONCLUSIONS ILR was equivalent at detecting ATAs when compared with Holter monitoring or ECG. However, the high rate of false-positive readings and the limited number of events available for review present barriers to broad implementation of this form of monitoring. Very few symptomatic events were AF on review.

Surgical ablation for atrial fibrillation: techniques, indications, and results.

Purpose of review The aim of this review is to focus specifically on the indications, evolution of technique, and results of surgical ablation for atrial fibrillation. Recent findings With the introduction of the Cox-Maze IV procedure utilizing bipolar radiofrequency ablation and cryoablation, long-term studies have demonstrated a significant decrease in aortic cross-clamp times and major complications with a comparable rate of restoration of sinus rhythm. New hybrid approaches utilizing both catheter-based ablation and minimally invasive surgical approaches have been developed, but have not been standardized. Early studies have demonstrated reasonable success rates of hybrid procedures, with advantages that include confirmation of conduction block, decreased surgical morbidity, and possibly reduced morbidity. However, hybrid approaches have the disadvantage of significantly increased operative times. Summary The Cox-Maze IV is currently the gold standard for surgical treatment of atrial fibrillation. New hybrid approaches have potential advantages with promising early results, but a standard lesion set, improvement in operative times, and long-term results still need to be evaluated.

Effectiveness of Surgical Ablation in Patients With Atrial Fibrillation and Aortic Valve Disease

BACKGROUND In patients with atrial fibrillation (AF), the addition of surgical ablation to aortic valve replacement (AVR) does not increase procedural morbidity or mortality. However, efficacy in this population has not been carefully evaluated. This study compared outcomes between patients undergoing stand-alone Cox-Maze IV with those undergoing surgical ablation and concomitant AVR. METHODS From January 2002 to May 2014, 188 patients received a stand-alone Cox-Maze IV (n = 113) or surgical ablation with concomitant AVR (n = 75). In the concomitant AVR group, patients underwent Cox-Maze IV (n = 58), left-sided Cox-Maze IV (n = 3), or pulmonary vein isolation (n = 14). Thirty-one perioperative variables were compared. Freedoms from AF on and off antiarrhythmic drugs were evaluated at 3, 6, 12, and 24 months. RESULTS Follow-up was available in 97% of patients. Freedom from AF on and off antiarrhythmic drugs in patients receiving a stand-alone Cox-Maze IV versus concomitant AVR was not significantly different at any time point. The concomitant AVR group had more comorbidities, paroxysmal AF, pacemaker implantations (24% vs 5%, p = 0.002), and complications (25% vs 5%, p < 0.001). Freedoms from AF off antiarrhythmic drugs for patients receiving an AVR and pulmonary vein isolation at 1 year was only 50%, which was significantly lower than patients receiving an AVR and Cox-Maze IV ( 94%, p = 0.001). CONCLUSIONS A Cox-Maze IV with concomitant AVR is as effective as a stand-alone Cox-Maze IV in treating AF, even in an older population with more comorbidities. Pulmonary vein isolation was not as effective and is not recommended in this population. A Cox-Maze IV should be considered in all patients undergoing AVR with a history of AF.

The impact of 6 weeks of atrial fibrillation on left atrial and ventricular structure and function

OBJECTIVE The impact of prolonged episodes of atrial fibrillation on atrial and ventricular function has been incompletely characterized. The purpose of this study was to investigate the influence of atrial fibrillation on left atrial and ventricular function in a rapid paced porcine model of atrial fibrillation. METHODS A control group of pigs (group 1, n = 8) underwent left atrial and left ventricular conductance catheter studies and fibrosis analysis. A second group (group 2, n = 8) received a baseline cardiac magnetic resonance imaging to characterize left atrial and left ventricular function. The atria were rapidly paced into atrial fibrillation for 6 weeks followed by cardioversion and cardiac magnetic resonance imaging. RESULTS After 6 weeks of atrial fibrillation, left atrial contractility defined by atrial end-systolic pressure-volume relationship slope was significantly lower in group 2 than in group 1 (1.1 ± 0.5 vs 1.7 ± 1.0; P = .041), whereas compliance from the end-diastolic pressure-volume relationship was unchanged (1.5 ± 0.9 vs 1.6 ± 1.3; P = .733). Compared with baseline, atrial fibrillation resulted in a significantly higher contribution of left atrial reservoir volume to stroke volume (32% vs 17%; P = .005) and lower left atrial booster pump volume contribution to stroke volume (19% vs 28%; P = .029). Atrial fibrillation also significantly increased maximum left atrial volume (206 ± 41 mL vs 90 ± 21 mL; P < .001). Left atrial fibrosis in group 2 was significantly higher than in group 1. Atrial fibrillation decreased left ventricular ejection fraction (29% ± 9% vs 58 ± 8%; P < .001), but left ventricular stroke volume was unchanged. CONCLUSIONS In a chronic model of atrial fibrillation, the left atrium demonstrated significant structural remodeling and decreased contractility. These data suggest that early intervention in patients with persistent atrial fibrillation might mitigate against adverse atrial and ventricular structural remodeling.

How I do it: Minimally invasive Cox-Maze IV procedure

Our patient is a 66-year-old female with a 2-year history of atrial fibrillation (AF) and mitral valve prolapse who presented with dyspnea on exertion. She was found to be in AF upon her admission electrocardiogram. A transthoracic echocardiogram was performed demonstrating moderateto-severe mitral regurgitation (MR) with a left atrial (LA) diameter of 5.1 cm and normal left ventricular (LV) function. After completion of her workup, it was decided that the patient would best be treated by a minimally invasive Cox-Maze IV (CMIV) and concomitant mitral valve procedure given her significant MR and symptoms. This article and accompanying video will discuss how the minimally invasive CMIV procedure is performed. Surgical techniques Preparation In order to perform a mini-thoracotomy mitral valve maze procedure, the patient is positioned with the right chest elevated 45° and the hips flat. Transesophageal echocardiography (TEE) is performed to assess the MR, and examine for a patent foramen ovale or clot in the LA appendage. The aortic valve is also evaluated since significant aortic insufficiency is a contraindication to this approach. The patient is prepped and draped in the usual fashion.

Pediatric Quality of Life while Supported with a Ventricular Assist Device

OBJECTIVE Ventricular assist devices (VADs) have emerged as an important treatment option for bridging pediatric patients with heart failure to transplant. VADs have shown improved survival; however, the pediatric quality of life (QoL) while on VAD support is unknown. We aimed to evaluate the QoL of our pediatric patients while supported with a VAD. DESIGN In this prospective study, pediatric patients who underwent VAD placement, and their parents, were administered a generic Pediatric Quality of Life Inventory (PedsQL) 4.0 pre-VAD implant, when feasible, after the acute postoperative period, and then periodically until heart transplant or death. Their final scores while on support were compared with three previously reported groups: healthy controls, outpatients with severe heart disease, and children after heart transplant. RESULTS From January 2008 to July 2014, 13 pediatric patients required VAD support greater than 2 weeks and completed a PedsQL. The mean age at implant was 10.0 ± 4.2 years and median duration of support was 1.6 (0.5-19.7) months. Eleven (85%) patients survived to transplant with one (8%) patient remaining alive on support. The median duration of support prior to their final PedsQL was 1.4 (0.5-11.4) months. Patients self-reported significantly (P < .05) lower total and physical QoL scores when compared with all three comparison groups. Self-reported psychosocial QoL scores were significantly lower than healthy controls only. Parent proxy-reported scores were significantly lower than all three comparison groups for all three categories (P < .05). CONCLUSIONS A large deficit exists in the total QoL of pediatric patients supported by a VAD compared with outpatient management of severe heart disease or postheart transplant patients; however, VAD patients do represent a group with more severe heart failure. Improvements in QoL must be made, as time spent with a VAD will likely continue to increase.

Right ventricular assist device with membrane oxygenator support for right ventricular failure following implantable left ventricular assist device placement

OBJECTIVES Cardiogenic shock from refractory right ventricular (RV) failure during left ventricular assist device placement is associated with high morbidity and mortality. The addition of extracorporeal membrane oxygenation to RV mechanical assistance may help RV recovery and lead to improved outcomes. METHODS We retrospectively reviewed all implanted continuous-flow left ventricular assist devices from April 2009 to June 2013. RV mechanical support was utilized for RV failure defined as haemodynamic instability despite vasopressors, pulmonary vascular dilators and inotropic therapy. RV assist devices were utilized with and without in-line membrane oxygenation. RESULTS During the study period, 267 continuous-flow left ventricular assist devices were implanted. RV mechanical support was utilized in 27 (10%) patients; 12 (46%) had the addition of in-line extracorporeal membrane oxygenation. The mean age of patients with a right ventricular assist device with membrane oxygenation was lower than that in patients with a right ventricular assist device alone (45.6 ± 15.9 vs 64.6 ± 6.5, P = 0.001). Support was weaned in 66% (10 of 15) of patients with right ventricular assist device (RVAD) alone vs 83% (10 of 12) of those with RVAD with membrane oxygenation (P = 0.42). The RVAD was removed after 10.4 ± 9.4 vs 5 ± 2.99 days for patients with a RVAD with membrane oxygenation (P = 0.1). Patients with RVAD with membrane oxygenation had a 30-day mortality rate of 8 vs 47% for those with RVAD alone (P = 0.04). The survival rate after discharge was 86, 63 and 54% at 3, 6 and 12 months for both groups combined. CONCLUSIONS Patients with a RVAD with membrane oxygenation support for acute RV failure after continuous-flow left ventricular assist device implantation had a lower 30-day mortality than those with a RVAD alone. Patients who survive to discharge have a reasonable 1-year survival. Combining membrane oxygenation with RVAD support appears to offer a short-term survival benefit in patients with RV failure after continuous-flow left ventricular assist device implantation.