Bradley G. Leshnower

Comparison of transfemoral transcatheter aortic valve replacement performed in the catheterization laboratory (minimalist approach) versus hybrid operating room (standard approach): outcomes and cost analysis.

OBJECTIVES The aim of this study was to compare transfemoral transcatheter aortic valve replacement (TF TAVR) performed in a catheterization laboratory (minimalist approach [MA]) with TF TAVR performed in a hybrid operating room (standard approach [SA]). BACKGROUND A MA-TF TAVR can be performed without general anesthesia, transesophageal echocardiography, or a surgical hybrid room. The outcomes and cost of MA-TF TAVR compared with those of the SA have not been described. METHODS Patients who underwent elective, percutaneous TF TAVR using the Edwards Sapien valve (Edwards Lifesciences, Irvine, California) were studied. Baseline characteristics, outcomes, and hospital costs of MA-TF TAVR and SA-TF TAVR were compared. RESULTS A total of 142 patients were studied (MA-TF TAVR, n = 70 and SA-TF TAVR, n = 72). There were no differences in baseline comorbidities (Society of Thoracic Surgeons score, 10.6 ± 4.3 vs. 11.4 ± 5.8; p = 0.35). All procedures in the MA-TF TAVR group were successful; 1 patient was intubated. Three patients in the SA-TF TAVR group had procedure-related death. Procedure room time (150 ± 48 min vs. 218 ± 56 min, p < 0.001), total intensive care unit time (22 h vs. 28 h, p < 0.001), length of stay from procedure to discharge (3 days vs. 5 days, p < 0.001), and cost (

Moderate Hypothermia and Unilateral Selective Antegrade Cerebral Perfusion: A Contemporary Cerebral Protection Strategy for Aortic Arch Surgery

45,485 ± 14,397 vs.

Video-Assisted Thoracoscopic Surgery Segmentectomy: A Safe and Effective Procedure

55,377 ± 22,587, p < 0.001) were significantly less in the MA-TF TAVR group. Mortality at 30 days was not significantly different in the MA-TF TAVR group (0 vs. 6%, p = 0.12) and 30-day stroke/transient ischemic attack was similar (4.3% vs. 1.4%, p = 0.35). Moderate or severe paravalvular leak and device success were similar in the MA-TF TAVR and SA-TF TAVR groups (3% vs. 5.8%, p = 0.4 and 90% vs. 88%, p = 0.79, respectively) at 30 days. At a median follow-up of 435 days, there was no significant difference in survival (MA-TF TAVR, 83% vs. SA-TF TAVR, 82%; p = 0.639). CONCLUSIONS MA-TF TAVR can be performed with minimal morbidity and mortality and equivalent effectiveness compared with SA-TF TAVR. The shorter length of stay and lower resource use with MA-TF TAVR significantly lowers hospital costs.

Single dose GLP-1-Tf ameliorates myocardial ischemia/reperfusion injury.

BACKGROUND Cerebral protection techniques during aortic arch surgery include deep hypothermic circulatory arrest, retrograde cerebral perfusion, and (or) antegrade cerebral perfusion. It is unclear whether unilateral selective antegrade cerebral perfusion (uSACP) in the setting of moderate hypothermic circulatory arrest (MHCA) constitutes an effective cerebral protective strategy during aortic arch reconstruction. METHODS A retrospective review was performed for all aortic arch cases involving uSACP between January 2004 and December 2009. Of these 412 patients, 97 (24%) were treated emergently. Adverse outcomes included operative mortality, permanent neurologic dysfunction, temporary neurologic dysfunction, and renal failure requiring dialysis. Potential selection bias was controlled by the inclusion of 11 covariates. Multivariable logistic regression analysis was used to model adverse outcome as a function of MHCA and the covariates. Adjusted odds ratios were formulated along with 95% confidence intervals. RESULTS Three hundred forty-four patients underwent hemiarch reconstruction and 68 patients underwent total arch replacement. The mean core body temperature at the initiation of uSACP was 25.7 degrees C + or - 2.8 degrees C with a uSACP time of 30 + or - 15 minutes. Overall operative mortality occurred in 29 (7.0%) patients. The incidence of permanent neurologic dysfunction and temporary neurologic dysfunction were 3.6% and 5.1%, respectively. Nineteen (4.6%) patients suffered postoperative renal failure requiring dialysis. In the adjusted analysis, MHCA was not found to be an independent predictor of mortality, permanent neurologic dysfunction, temporary neurologic dysfunction, or renal failure requiring dialysis. CONCLUSIONS The MHCA with adjunctive uSACP is not an independent risk factor for adverse outcomes after aortic arch surgery. These data suggest that MHCA combined with uSACP represents an effective cerebral protective strategy in patients undergoing arch reconstruction in both the elective and emergent settings.

Hemiarch Replacement at 28°C: An Analysis of Mild and Moderate Hypothermia in 500 Patients

BACKGROUND Anatomic sublobar resection is currently being assessed as an alternative to lobectomy for primary lung cancers less than 2 cm in size. Open segmentectomy is a proven oncologic procedure for patients with reduced cardiopulmonary reserve and significant comorbidities. With the increased use of thoracoscopy, a video-assisted thoracoscopic surgery (VATS) segmentectomy may be as safe and effective as an open segmentectomy. METHODS We performed a retrospective review of patients who underwent a segmentectomy between May 2002 and March 2009 at Emory University Hospital. RESULTS Forty-one patients underwent pulmonary segmentectomy; 26 through thoracotomy (open) and 15 by a thoracoscopic (VATS) approach. Both groups were well matched for age, gender, and preoperative risk factors. Segmentectomy was performed for primary lung cancer in 25 (61%) patients. There was no difference in tumor size, number of lymph node stations sampled, or number of lymph nodes removed based upon approach. The remaining indications for surgery were metastatic disease in 12 patients and benign disease in 4 patients. All patients underwent R0 resections. There was no significant difference in operative time, but patients undergoing a VATS segmentectomy had significantly reduced chest tube durations and hospital stays. Major complications occurred in 19% of patients in the open group and none in the VATS group. There were two operative deaths (4.8%), both in the open group. CONCLUSIONS Video-assisted thoracoscopic surgery segmentectomy is a safe procedure which has fewer complications and a reduced hospital stay when compared with an open segmentectomy. This approach may be the ideal oncologic procedure for patients with small lung cancers (<2 cm) and (or) limited cardiopulmonary reserve and significant comorbidities.

Mild Hypothermia to Limit Myocardial Ischemia-Reperfusion Injury: Importance of Timing

BACKGROUND Glucagon-like peptide-1 (GLP-1) has insulinomimetic, insulinotropic, and antiapoptotic properties that may make it a useful adjunct to reperfusion therapy for myocardial infarction (MI); however, GLP-1 has a short plasma half-life. Fusion of GLP-1 to human transferrin (GLP-1-Tf) significantly prolongs drug half-life. MATERIALS AND METHODS We tested the ability of single dose GLP-1-Tf to limit myocardial ischemia (30 min)/reperfusion (180 min) injury in rabbits. Nineteen animals were untreated controls. The pre-ischemic group (n=10) was given 10mg/kg of GLP-1-Tf 12 h before ischemia. Immediately after reperfusion, the post-ischemic group (n=10) received GLP-1-Tf (10 mg/kg) and the Tf group (n=4) received transferrin alone. RESULTS Infarct size as a percentage of the area at risk was 59.1% ± 1.3%, 45.7% ± 1.9%, 44.1% ± 3.3%, 59.7% ± 2.0% in the control group, pre-ischemic group, post-ischemic group, and Tf group, respectively (P<0.05 for both GLP-1-Tf treatments group versus control). GLP-1-Tf reduced the apoptotic index from 4.67% ± 0.40% in the control group to 3.15% ± 0.46% in the pre-ischemic group and to 2.66% ± 0.40% in the post-ischemic group (P<0.05 for both GLP-1-Tf treatments versus control). The size of the wall motion abnormality and ejection fraction was significantly improved in the post-ischemic group relative to the control group. Serum GLP-1 levels were 239.8 ± 25.7 μg/mL in the post-ischemic group, 27.9 ± 5.8 μg/mL in the pre-ischemic group, and undetectable in the control group. CONCLUSION GLP-1-Tf limits myocardial reperfusion injury whether given prior to the onset of ischemia or given at reperfusion. GLP-1-Tf may also limit myocardial stunning at high serum levels of the drug.

Cyclosporine Preserves Mitochondrial Morphology After Myocardial Ischemia/Reperfusion Independent of Calcineurin Inhibition

BACKGROUND During the past decade, use has increased of moderate hypothermic circulatory arrest with antegrade cerebral perfusion for cerebral protection during aortic arch operations. This study examined the use of mild hypothermia in conjunction with unilateral selective antegrade cerebral perfusion (uSACP) for hemiarch replacement for proximal aortic arch reconstruction. METHODS A retrospective review of the Emory Aortic Database identified 708 patients who underwent aortic arch replacement between 2004 and 2011. Of these, 500 underwent hemiarch replacement at temperatures of 22°C or higher with uSACP. Outcomes were analyzed and compared between 277 patients undergoing hemiarch at a temperature of 28.6°C (mild) and 233 undergoing hemiarch at a temperature of 24.3°C (moderate). Propensity scores were generated and analyzed between the groups to adjust for confounding factors such as selection bias. RESULTS Operative mortality was equivalent between mild and moderate groups in elective (4.2% vs 4.8%, p=0.80) and emergency (7.7% vs 11.7%, p=0.43) settings. No differences occurred in the incidence of temporary neurologic dysfunction, dialysis-dependent renal failure, or mediastinal reexploration for bleeding between mild and moderate patients. The incidence of permanent neurologic deficit was significantly reduced in mild (2.5%) vs moderate patients (7.2%, p=0.01), which was confirmed by the propensity score analysis (adjusted odds ratio, 0.28; p=0.02). CONCLUSIONS Hemiarch replacement can be safely performed at 28°C with uSACP in emergency and elective settings. Mild hypothermia with uSACP offers adequate levels of neurologic protection compared with deeper levels of hypothermia.

Quantifying Acute Myocardial Injury Using Ratiometric Fluorometry

BACKGROUND Hypothermia during ischemia has been shown to reduce myocardial reperfusion injury. We sought to establish the cardioprotective effect of very mild total-body hypothermia (<or= 2.5 degrees C) and to determine whether the application of hypothermia at different points during the ischemia-reperfusion period influenced the degree of myocardial salvage. METHODS Rabbits were subjected to 30 minutes of myocardial ischemia followed by 3 hours of reperfusion. Twenty-five animals were maintained at normal temperature (39.5 degrees C) throughout the experiment (W-W-W group). All other animals were cooled to reduce left atrial temperature 2.0 degrees C to 2.5 degrees C. Eleven animals reached goal temperature before coronary occlusion (C-C-C group), in 14 animals cooling was initiated at coronary occlusion (W-C0-C group), in 8 animals cooling was initiated 15 minutes after coronary occlusion (W-C15-C group), in 5 animals cooling was initiated 25 minutes after coronary occlusion (W-C25-C group), and in 13 animals cooling was started concurrently with reperfusion (W-W-C group). Infarct size as a percentage of the risk area (I/AR) was determined by a double staining-planimetry technique. RESULTS Goal temperature was achieved before reperfusion in the C-C-C and W-C0-C groups but was not achieved until the reperfusion period in the other treatment groups. Infarct size was 59.0 +/- 1.2% in the W-W-W group and was reduced in all cooling groups (C-C-C = 30.4 +/- 4.9%; W-C0-C = 33.4 +/- 5.0%; W-C15-C = 42.4 +/- 1.4%; W-C25-C = 44.1 +/- 2.3%; W-W-C = 50.5 +/- 4.1%). The temperature at reperfusion correlated most strongly with infarct size (r = 0.72, p < 1 x 10(-12)). CONCLUSIONS Very mild hypothermia affords a significant cardioprotective effect. Temperature at the time of reperfusion most strongly correlates with the degree of myocardial salvage.

Very Mild Hypothermia During Ischemia and Reperfusion Improves Postinfarction Ventricular Remodeling

BACKGROUND Opening of the mitochondrial permeability transition pore (MPTP) has been shown to contribute to myocardial ischemia/reperfusion injury. We sought to demonstrate that the myocardial protective effect of inhibiting MPTP opening with cyclosporine A (CsA) results in stabilization of mitochondrial morphology and is independent of CsA-induced calcineurin inhibition. METHODS Thirty-seven rabbits were divided into three groups: control (n = 15), CsA (MPTP and calcineurin inhibitor, n = 12), or FK506 (calcineurin inhibitor, n = 10). Each group received a 1-hour infusion of either a saline vehicle, 25 mg/kg CsA or 1 mg/kg FK506. All animals underwent 30 minutes of regional ischemia and 3 hours of reperfusion. Myocardial infarct size was determined using Evans blue dye and triphenyltetrazolium chloride. In situ oligo ligation was used to assess apoptotic cell death. Transmission electron microscopy was used to quantitatively evaluate morphologic differences in the mitochondria between groups. RESULTS Infarct size in the CsA group (39% +/- 3%) was significantly reduced compared with the control group (60% +/- 2%, p < 0.001) and FK506 group (55% +/- 3%, p = 0.001). Apoptotic cell death was also attenuated in the CsA group (1.2% +/- 0.5%) compared with the control group (4.3% +/- 0.8%, p = 0.01) and FK506 group (4.1% +/- 0.9%, p = 0.05). Transmission electron microscopy revealed a preservation of normal mitochondrial morphology and a reduction in the percentage of disrupted mitochondria in the CsA group (20% +/- 7%) compared with the control group (53% +/- 12%) and FK506 group (47% +/- 9%). CONCLUSIONS Cyclosporine A-induced MPTP inhibition preserves mitochondrial morphology after myocardial ischemia/reperfusion and limits myocyte necrosis and apoptosis. These effects are independent of calcineurin inhibition.

Acute Type A Dissection: Impact of Antegrade Cerebral Perfusion Under Moderate Hypothermia

Early reperfusion is the best therapy for myocardial infarction (MI). Effectiveness, however, varies significantly between patients and has implications for long-term prognosis and treatment. A technique to assess the extent of myocardial salvage after reperfusion therapy would allow for high-risk patients to be identified in the early post-MI period. Mitochondrial dysfunction is associated with cell death following myocardial reperfusion and can be quantified by fluorometry. Therefore, we hypothesized that variations in the fluorescence of mitochondrial nicotinamide adenine dinucleotide (NADH) and flavoprotein (FP) can be used acutely to predict the degree of myocardial injury. Thirteen rabbits had coronary occlusion for 30 min followed by 3 h of reperfusion. To produce a spectrum of infarct sizes, six animals were infused cyclosporine A prior to ischemia. Using a specially designed fluorometric probe, NADH and FP fluorescence were measured in the ischemic area. Changes in NADH and FP fluorescence, as early as 15 min after reperfusion, correlated with postmortem assessment infarct size (r=0.695, p<0.01). This correlation strengthened with time (r=0.827, p<0.01 after 180 min). Clinical application of catheter-based myocardial fluorometry may provide a minimally invasive technique for assessing the early response to reperfusion therapy.