John R. Handy

Increased Matrix Metalloproteinase Activity and Selective Upregulation in LV Myocardium From Patients With End-Stage Dilated Cardiomyopathy

Background —One of the hallmarks of dilated cardiomyopathy (DCM) is left ventricular (LV) remodeling. The matrix metalloproteinases (MMPs) are a family of enzymes that contribute to extracellular remodeling in several disease states. Additionally, a family of inhibitors called tissue inhibitors of MMPs (TIMPs) has been shown to exist and to tightly regulate MMP activity. However, the types of MMPs and TIMPs expressed within the normal and DCM LV myocardium and the relation to MMP activity remain unexplored. Methods and Results —Relative LV myocardial MMP activity was determined in the normal (n=8) and idiopathic DCM (n=7) human LV myocardium by substrate zymography. Relative LV myocardial abundance of interstitial collagenase (MMP-1), stromelysin (MMP-3), 72 kD gelatinase (MMP-2), 92 kD gelatinase (MMP-9), TIMP-1, and TIMP-2 were measured with quantitative immunoblotting. LV myocardial MMP zymographic activity increased with DCM compared with normal (984±149 versus 413±64 pixels, P 500% with DCM. A high-molecular-weight immunoreactive band for both TIMP-1 and TIMP-2, suggesting a TIMP/MMP complex, was increased >600% with DCM. Conclusions —This study demonstrated increased LV myocardial MMP activity and evidence for independent regulatory mechanisms of MMP and TIMP expression with DCM. These findings suggest that selective inhibition of MMP species within the LV myocardium may provide a novel therapeutic target in patients with DCM.

American College of Chest Physicians and Society of Thoracic Surgeons Consensus Statement for Evaluation and Management for High-Risk Patients with Stage I Non-small Cell Lung Cancer

BACKGROUND The standard treatment of stage I non-small cell lung cancer (NSCLC) is lobectomy with systematic mediastinal lymph node evaluation. Unfortunately, up to 25% of patients with stage I NSCLC are not candidates for lobectomy because of severe medical comorbidity. METHODS A panel of experts was convened through the Thoracic Oncology Network of the American College of Chest Physicians and the Workforce on Evidence-Based Surgery of the Society of Thoracic Surgeons. Following a literature review, the panel developed 13 suggestions for evaluation and treatment through iterative discussion and debate until unanimous agreement was achieved. RESULTS Pretreatment evaluation should focus primarily on measures of cardiopulmonary physiology, as respiratory failure represents the greatest interventional risk. Alternative treatment options to lobectomy for high-risk patients include sublobar resection with or without brachytherapy, stereotactic body radiation therapy, and radiofrequency ablation. Each is associated with decreased procedural morbidity and mortality but increased risk for involved lobe and regional recurrence compared with lobectomy, but direct comparisons between modalities are lacking. CONCLUSIONS Therapeutic options for the treatment of high-risk patients are evolving quickly. Improved radiographic staging and the diagnosis of smaller and more indolent tumors push the risk-benefit decision toward parenchymal-sparing or nonoperative therapies in high-risk patients. Unbiased assessment of treatment options requires uniform reporting of treatment populations and outcomes in clinical series, which has been lacking to date.

Is Obesity a Risk Factor for Mortality in Coronary Artery Bypass Surgery

Background—The published articles examining obesity and CABG surgery contain conflicting results about the role of body mass index (BMI) as a risk factor for in-hospital mortality. Methods and Results—We studied 16 218 patients who underwent isolated CABG in the Providence Health System Cardiovascular Study Group database from 1997 to 2003. The effect of BMI on in-hospital mortality was assessed by logistic regression, with BMI group (underweight, normal, overweight, and 3 subgroups of obesity) as a categorical variable or transformations, including fractional polynomials, of BMI as a continuous variable. BMI was not a statistically significant risk factor for mortality in any of these assessments. However, using cumulative sum techniques, we found that the lowest risk-adjusted CABG in-hospital mortality was in the high-normal and that overweight BMI subgroup patients with lower or higher BMI had slightly increased mortality. Conclusions—Body size is not a significant risk factor for CABG mortality, but the lowest mortality is found in the high-normal and overweight subgroups compared with obese and underweight.

Propensity Score Analysis of Stroke After Off-Pump Coronary Artery Bypass Grafting

2.5% of on-pump patients and only 1.2% of off-pump CABG patients, for an (unadjusted) odds ratio (OR) of 2.1 for on-pump versus off-pump CABG (see Appendix for definition of OR). Because the two patient groups were not similar with respect to potential risk factors for stroke, they used a logistic regression, which produced an adjusted OR of 1.6. As an adjunctive analysis, they computed a propensity score and used it to find on-pump matches for 72% of the off-pump CABG patients. For these matched subsets the OR for postoperative stroke was 1.8. This expository article briefly describes propensity scores and demonstrates another way of using them to compare treatments. We apply this method to another data set, and in the process corroborate the findings of Stamou and colleagues.

Hospital readmission after pulmonary resection: prevalence, patterns, and predisposing characteristics

BACKGROUND Our objective was to define the prevalence, patterns, and predisposing characteristics for hospital readmission after pulmonary resection. METHODS Five years of pulmonary resections, excluding lung biopsies, were analyzed from a prospective, computerized database. Readmission was defined as inpatient or emergency department admission within 90 days of operation. Search of 1,173,912 admissions to the Providence Health System in Oregon identified readmissions. Readmission analysis excluded operative deaths. RESULTS A total of 374 patients underwent pulmonary resections, of whom 8 died (2.1%). Of 366 patients discharged, 69 (18.9%) were readmitted a total of 113 times: 42 had only one readmission, 16 had two readmissions, 7 had three readmissions, 2 had four readmissions, and 2 had five readmissions. Slightly more than half (51%) were readmitted as inpatients. Causes of the 113 readmissions included pulmonary (27%), postoperative infection (14%), cardiac (7%), and other (16%). Mean time to readmission was 32.5 +/- 24.6 days. Inpatient readmission mean length of stay was 4.9 +/- 3.4 days. Readmission to hospitals other than the hospital of the operation was as follows: first readmission, 15.9%; second readmission, 14.8%; third readmission, 36.3%; fourth readmission, 25%; fifth readmission, 0%. Analysis revealed only pneumonectomy as a risk for readmission. Twelve of 33 (36%) pneumonectomies were readmitted (p = 0.005). Of the 297 patients discharged after pulmonary resection and not requiring readmission, 12 (4%) died over the study interval, whereas 8 of 69 patients (11.6%) requiring readmission died. CONCLUSIONS Readmission after pulmonary resection is frequent and multiple readmissions are common. Causes are predominately pulmonary diagnoses and infections related to the operation. Pneumonectomy is a risk for readmission. An important portion of readmissions occurs outside the hospital of operation. The population requiring readmission after successfully undergoing pulmonary resection is at increased risk of subsequent mortality.

Median sternotomy versus thoracotomy to resect primary lung cancer: analysis of 815 cases

BACKGROUND We sought to determine if median sternotomy (MS) is an equivalent incision to thoracotomy (TH) in the treatment of primary pulmonary carcinoma. METHODS We followed 801 patients undergoing 815 operations for primary lung carcinoma in a computer registry; 447 had MS, 368 had TH. RESULTS Both groups were similar in preoperative risk assessment. Complete staging lymph node dissections were performed in 42% of MS patients and 17% of TH patients. Operative mortality (3.8% for MS, 3.3% for TH) and postoperative complications were similar. MS patients had a shorter postoperative hospital stay (7.5 days vs. 8.2 days). One hundred thirty-nine underwent pneumonectomy. Operative mortality was 12.5% for MS and 10.4% for TS (p = NS). Five hundred eighty-one underwent lobectomy with an operative mortality of 2.1% for MS and 2.0% for TH. Mean length of stay for MS lobectomy was 7.5 days compared with 8.5 days for TH (p = 0.06). Follow-up was 89% through 1998, comprising 1,339 MS and 1,463 TH patient-years. Survival for stage I at 5 and 10 years, respectively, was 51% and 34% for MS vs 54% and 32% for TH (p = NS). Survival for other stages was also similar. CONCLUSIONS Median sternotomy provides more complete staging, shorter postoperative hospitalization, and better patient acceptance with equivalent operative and long-term survival when compared with thoracotomy. Concerns regarding increased wound infections in MS patients appear unfounded.

Hypothermic potassium cardioplegia impairs myocyte recovery of contractility and inotropy

Acute postoperative left ventricular dysfunction after hypothermic, crystalloid potassium cardioplegia occasionally occurs. This project examined myocyte contractility and inotropic responsiveness after hypothermic arrest with and without potassium cardioplegia. Isolated swine left ventricular myocytes were placed in a thermostatically controlled chamber (37 degrees C) that contained a standard cell medium, pulse stimulated at 1 Hz, and steady-state contractions were measured by computer-assisted video microscopy with and without isoproterenol (25 nmol/L). After baseline measurements were taken the myocytes were randomly assigned to the following treatments: (1) control group with infusion of 37 degrees C crystalloid solution and maintained at 37 degrees C for 3 hours (n = 23), (2) hypothermia group with infusion of 4 degrees C crystalloid without potassium and stored at 4 degrees C for 3 hours (n = 22), (3) hypothermic cardioplegia group with infusion of a crystalloid cardioplegia (oxygenated, buffered 4 degrees C Ringers solution with 24 mEq/L K+) and then stored at 4 degrees C for 3 hours (n = 35). After treatment the myocytes were then rewarmed to 37 degrees C by infusion of medium, and contractile measurements were repeated. In the control group, the percent and velocity of shortening were identical to those in baseline measurements: 6.4% +/- 0.4% and 53 +/- 5 microns/sec, respectively, and these values remained unchanged in the hypothermia group: 6.5% +/- 0.4% and 51 +/- 3 microns/sec, respectively. However, in the hypothermic cardioplegia group, the percent and velocity of shortening were significantly lower with rewarming: 4.8% +/- 0.4% and 35 +/- 3 microns/sec, respectively, p < 0.05). Isoproterenol caused increased percent and velocity of shortening in both the control and hypothermia groups: 10.0% +/- 0.6% and 9.5% +/- 0.9% and 81.6 +/- 8 microns/sec and 71.4 +/- 8 microns/sec, respectively. This response was significantly blunted in the cardioplegia group (8.9% +/- 0.8% and 56.9 +/- 7 microns/sec, p < 0.05). With an isolated myocyte system that is independent of extracellular and perfusion effects, hyperkalemic cardioplegic solution resulted in depressed myocyte contractile performance after rewarming. Potassium cardioplegia also caused a blunted inotropic responsiveness on rewarming. A potential contributory factor for the depressed left ventricular function after the use of potassium cardioplegia is a direct depression in myocyte contractility.

Aortoesophageal fistula and double aortic arch: Two important points in management

Two children with double aortic arch and aortoesophageal fistula (AEF) are reported to warn of this lethal complication of double aortic arch and to stress important points in the diagnosis and management. A review of the records of 30 children with double aortic arch disclosed two patients who had AEF. The first patient had respiratory distress and repair of a vascular ring (double aortic arch) at 5 weeks of age. At 9 weeks of age, because of difficulty with tracheal extubation, aortopexy was performed. Ten days later, profuse upper gastrointestinal bleeding required control by a Sengstaken-Blakemore (SB) tube. Thoracotomy and repair AEF was accomplished successfully under cardiopulmonary bypass. The second patient had hepatomegaly and Pseudomonas sepsis. Endotracheal and nasogastric intubation was necessary, and subsequently the double aortic arch was demonstrated by magnetic resonance imaging (MRI). On the 48th day of hospitalization, life-threatening upper gastrointestinal hemorrhage required insertion of an SB tube. Cardiopulmonary bypass allowed successful repair of the AEF. Both children are alive, after 3 and 2 years (respectively). These patients demonstrate that AEF must be diagnosed clinically (no imaging technique is effective); its history and physical presentation are typical. The SB tube is effective for controlling the hemorrhage until cardiopulmonary bypass can be performed to allow repair.

Pneumoperitoneum to Treat Air Leaks and Spaces After a Lung Volume Reduction Operation

Lung volume reduction surgery is an option for the management of end-stage emphysema. The most frequent surgical complication of lung volume reduction is prolonged air leaks. We describe a patient undergoing a lung volume reduction operation complicated by persistent bilateral air spaces with large air leaks. Treatment with recurrent pneumoperitoneum via a peritoneal dialysis catheter along with chemical sclerosis successfully resolved both problems.

Thoracic epidural anesthesia as the last option for treating angina in a patient before coronary artery bypass surgery.

I schemic cardiomyopathy in a patient with medically refractory unstable angina is a difficult clinical scenario. Unfavorable anatomy and/or comorbidity can prohibit the safe performance of angioplasty or coronary artery bypass (CAB) surgery. Thoracic epidural anesthesia (TEA) has been used successfully to stabilize patients with unstable angina refractory to maximum medical therapy (1). TEA has also been used during and after CAB surgery in patients with preserved left ventricular function (2,3). We describe a patient with intractable angina, poor ventricular function, and complicated comorbidities who received TEA for angina, later underwent CAB surgery using TEA in combination with general anesthesia, and continued to receive TEA for postoperative pain relief.