Alexander P.W.M. Maat

Prediction of Improvement of Regional Left Ventricular Function After Surgical Revascularization A Comparison of Low-Dose Dobutamine Echocardiography With 201Tl Single-Photon Emission Computed Tomography

BACKGROUNDnAlthough both 201Tl scintigraphy and low-dose dobutamine echocardiography (LDDE) have been proposed as effective methods of assessing myocardial viability, their relative efficacies are unknown. The aim of the present study was to compare the two imaging techniques in the prediction of improvement of regional left ventricular (LV) function after surgical revascularization.nnnMETHODS AND RESULTSnThirty-eight patients with severe chronic LV dysfunction (ejection fraction < or = 40%, one or more akinetic [Ak] or severely hypokinetic [SH] segments on resting echocardiogram) who underwent uncomplicated coronary artery bypass graft surgery were studied with simultaneous dobutamine stress echocardiography and poststress reinjection 201Tl single-photon emission computed tomography (SPECT) before surgery. The Ak or SH segments were considered viable by LDDE when wall thickening improved during the infusion of 10 micrograms.kg-1 min 1 dobutamine. Scintigraphic definition of viability was the presence of normal 201Tl uptake, totally reversible defect, partially reversible defect, or moderately severe fixed defect. The postoperative improvement of dyssynergic segments was determined with a rest echocardiogram 3 months after surgery. Of 608 LV segments, 169 were classified as Ak and 51 as SH on resting preoperative echocardiography. Of these, 170 were successfully revascularized. Wall motion during LDDE improved in 33 severely dyssynergic segments and was more frequent in SH than in Ak segments (19 of 44 versus 14 of 126, P < .0001). Viability was detected by 201Tl SPECT criteria in 103 SH or Ak segments. Thirty-two of the 33 segments from LDDE responders were judged viable on 201Tl SPECT, whereas 201Tl viability was also detected in 71 of 137 segments from LDDE nonresponders. The sensitivity and the specificity for the prediction of postoperative improvement of segmental wall motion were 74% (95% confidence interval [CI], 67% to 81%) and 95% (95% CI, 92% to 98%) by LDDE and 89% (95% CI, 84% to 94%) and 48% (95% 40% to 56%) by 201Tl SPECT, respectively. Positive predictive value of LDDE was higher than that of 201Tl SPECT (85%, [95% CI, 80% to 90%] versus 33% [95% CI, 26% to 40%]). Thirty-six patients had angina before and only 1 had angina 3 months after revascularization. High-dose dobutamine echocardiography demonstrated significant reduction in stress-induced ischemia (new or worsening of preexisting wall motion abnormalities) after surgery (from 163 to 23 LV segments).nnnCONCLUSIONSnIn patients with severe chronic LV dysfunction, LDDE is a good predictor of the improvement of dyssynergic segments after revascularization. Because 201Tl SPECT overestimates the probability of postoperative improvement of dyssynergic segments, LDDE should be the preferred imaging technique for preoperative assessment of these patients.

Reduction of Surgical-Site Infections in Cardiothoracic Surgery by Elimination of Nasal Carriage of Staphylococcus aureus

OBJECTIVEnTo test the hypothesis that perioperative elimination of nasal carriage of Staphylococcus aureus using mupirocin nasal ointment reduces the surgical-site infection (SSI) rate in cardiothoracic surgery.nnnDESIGNnUnblinded intervention trial with historical controls.nnnSETTINGnA university hospital, tertiary referral center for cardiothoracic surgery.nnnPATIENTSnConsecutive patients undergoing cardiothoracic surgery between August 1, 1989, and February 1, 1991 (historical control group), and between March 1, 1991, and August 1, 1992 (intervention group).nnnRESULTSnThe historical control group consisted of 928 patients and the intervention group of 868, of whom 752 actually were treated. The 116 patients who were unintentionally not treated were considered as a concurrent control group. In the intention-to-treat analysis, a significant reduction in SSI rate was observed after the intervention (historical-control group 7.3% and intervention group 2.8%; P < .0001). The SSI rate in the concurrent control group was significantly higher than in the treated group (7.8% and 2.0%, respectively; P = .0023). Resistance of S aureus to mupirocin was not observed.nnnCONCLUSIONnThe results of this study indicate that perioperative elimination of nasal carriage using mupirocin nasal ointment significantly reduces the SSI rate in cardiothoracic surgery patients and warrants a prospective, randomized, placebo-controlled efficacy trial. This preventive measure may be beneficial in other categories of surgical patients as well.

Validation of the Charlson comorbidity index in patients with operated primary non-small cell lung cancer.

OBJECTIVEnTo validate the influence of the Charlson comorbidity index (CCI) in patients with operated primary non-small cell lung cancer.nnnMETHODSnFrom January 1996 to December 2001, 205 consecutive resections for non-small cell lung cancer were performed at the Erasmus Medical Center Rotterdam. The patients ranged in age from 29 to 82 years, with a mean age of 64 years. In a retrospective study, each patient was scaled according to the CCI and the complications of surgery were determined.nnnRESULTSnThe hospital mortality was 2.4% (5/205). Of the 205 patients 167 (32.7%) experienced minor complications and 32 (15.6%) major complications. In univariate analysis, gender, grades 3-4 of the CCI, any prior tumor treated in the last 5 years and chronic pulmonary disease were significant predictors of adverse outcome. Multivariate analysis showed that only grades 3-4 of the CCI was predictive (odds ratio=9.8; 95% confidence interval=2.1-45.9). Although only comorbidity grades 3-4 was a significant predictor, for every increase of the comorbidity grade the relative risk of adverse outcome showed a slight increase.nnnCONCLUSIONnThe CCI is strongly correlated with higher risk of surgery in primary non-small cell lung cancer patients and is a better predictor than individual risk factors.

Biphasic response to dobutamine predicts improvement of global left ventricular function after surgical revascularization in patients with stable coronary artery disease: Implications of time course of recovery on diagnostic accuracy

OBJECTIVESnThis study sought to evaluate the time course of improvement of left ventricular (LV) dysfunction in stable patients and its implications on the accuracy of dobutamine echocardiography for predicting improvement after surgical revascularization.nnnBACKGROUNDnLittle is known about the optimal timing for evaluation of postrevascularization recovery of the contractile function of viable myocardium.nnnMETHODSnSixty-one patients with chronic ischemic LV dysfunction scheduled for elective surgical revascularization were prospectively selected. They underwent dobutamine echocardiography (5 to 40 microg/kg body weight per min) and radionuclide ventriculography both preoperatively and at 3-month follow-up. At 14 months, another evaluation of LV function was obtained. To analyze echocardiograms, a 16-segment model and a five-point scoring system were used. Dyssynergic segments were considered likely to recover in the presence of a biphasic contractile response to dobutamine. Improvement of global function was defined as a > or =5% increase in LV ejection fraction (LVEF).nnnRESULTSnOf the 61 patients, LVEF improved in 12 at 3 months and in 19 at late follow-up (from 32+/-8% to 42+/-9%, p < 0.0001). The frequency and time course of improvement of LVEF were similar in patients with mild and severe LV dysfunction. A biphasic response, identified in 186 of the 537 dyssynergic segments, was predictive of recovery in 63% at 3 months and in 75% at late follow-up. The positive predictive value was best in the most severe dyssynergic segments (90% vs. 67%). Other responses were highly predictive for nonrecovery (92%). The sensitivity and specificity for improvement of global function on a patient basis (> or =4 biphasic segments) were 89% and 81%, respectively, at late follow-up.nnnCONCLUSIONSnSerial postoperative follow-up studies demonstrate incomplete recovery of contractile function at 3 months. The diagnostic accuracy of dobutamine echocardiography for predicting recovery is dependent on three factors: the combining of low and high dobutamine dosages, the severity of regional dyssynergy and the timing of evaluation.

Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial

The European Organisation for Research and Treatment of Cancer (EORTC; protocol 08031) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma (with a severity of cT3N1M0 or less). Induction chemotherapy consisted of three courses of cisplatin 75 mg·m−2 and pemetrexed 500 mg·m−2. Nonprogressing patients underwent extrapleural pneumonectomy followed by post-operative radiotherapy (54 Gy, 30 fractions). Our primary end-point was “success of treatment” and our secondary end-points were toxicity, and overall and progression-free survival. 59 patients were registered, one of whom was ineligible. Subjects’ median age was 57 yrs. The subjects’ TNM scores were as follows: cT1, T2 and T3, 36, 16 and six patients, respectively; cN0 and N1, 57 and one patient, respectively. 55 (93%) patients received three cycles of chemotherapy with only mild toxicity. 46 (79%) patients received surgery and 42 (74%) had extrapleural pneumonectomy with a 90-day mortality of 6.5%. Post-operative radiotherapy was completed in 37 (65%) patients. Grade 3–4 toxicity persisted after 90 days in three (5.3%) patients. Median overall survival time was 18.4 months (95% CI 15.6–32.9) and median progression-free survival was 13.9 months (95% CI 10.9–17.2). Only 24 (42%) patients met the definition of success (one-sided 90% CI 0.36–1.00). Although feasible, trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary.

Extensive Left Ventricular Remodeling Does Not Allow Viable Myocardium to Improve in Left Ventricular Ejection Fraction After Revascularization and Is Associated With Worse Long-Term Prognosis

Background—Extensive left ventricular (LV) remodeling may not allow functional recovery after revascularization, despite the presence of viable myocardium. Methods and Results—Seventy-nine consecutive patients with ischemic cardiomyopathy (left ventricle ejection fraction [LVEF] 29±7%) underwent surgical revascularization. Before revascularization, viability was assessed by metabolic imaging with F18-fluorodeoxyglucose and SPECT. LV volumes and LVEF were assessed by resting echocardiography. LVEF was re-assessed by echocardiography 8 to 12 months after revascularization. Three-year clinical follow-up (events: cardiac death, infarction, and hospitalization for heart failure) was also obtained. Forty-nine patients had substantial viability; 5 died before re-assessment of LVEF. Of the remaining 44 patients, 24 improved ≥5% in LVEF after revascularization, whereas 20 did not improve in LVEF. LV end-systolic volume was the only parameter that was significantly different between the groups (109±46 mL for the improvers versus 141±31 mL for the nonimprovers; P<0.05). The change in LVEF after revascularization was linearly related to the baseline LV end-systolic volume, with a higher LV end-systolic volume associated with a low likelihood of improvement in LVEF after revascularization. During the 3-year follow-up, the highest event-rate (67%) was observed in patients without viable myocardium with a large LV size, whereas the lowest event rate (5%) was observed in patients with viable myocardium and a small LV size. Intermediate event rates were observed in patients with viable myocardium and a large LV size (38%), and in patients without viable myocardium and a small LV size (24%). Conclusion—Extensive LV remodeling prohibits improvement in LVEF after revascularization and affects long-term prognosis negatively, despite the presence of viability.

Lung resection for non–small-cell lung cancer in patients older than 70: mortality, morbidity, and late survival compared with the general population

BACKGROUNDnOperative mortality and morbidity in elderly patients operated on for non-small-cell lung cancer are acceptable. However, risk factors for hospital mortality and the benefits for the patients in the long term are insufficiently defined, and survival compared with the general population is not known.nnnMETHODSnFrom January 1989 to October 2001, 126 consecutive patients older than 70 years of age underwent resection for non-small-cell lung cancer. Each patient was scaled according to the Charlson Comorbidity Index. Postoperative events were divided into minor and major complications. Risk factors for complications and long-term survival were assessed by univariate and multivariate logistic regression analysis. Survival was compared with the yearly expected survival rates of the general population.nnnRESULTSnThe hospital mortality was 3.2%. Minor complications occurred in 71 (57%) patients, major complications, in 16 (13%) patients. No risk factor was predictive for major complications. However, a Charlson comorbidity grade of 3 to 4 was predictive for major complications (odds ratio, 12.6; 95% confidence interval, 1.5 to 108.6). Our study showed a 5- and 10-year survival rate of 37% (95% confidence interval, 23 to 51) and 15% (95% confidence interval, 8 to 22). Smoking (odds ratio, 2.3), chronic obstructive pulmonary disease (odds ratio, 2.1), and pathologic stage IIIA (odds ratio, 2.2) or IIIB (odds ratio, 11.9) were risk factors for long-term survival. The observed survival was lower than the expected survival, but the difference decreased with increasing time after pulmonary resection.nnnCONCLUSIONSnPulmonary resection for non-small-cell lung cancer in patients older than 70 years shows acceptable morbidity and mortality. The Charlson index is a better predictor of complications than individual risk factors. In time survival is no longer correlated with the disease but follows the same pattern as the general population.

Raman microspectroscopic mapping studies of human bronchial tissue

Characterization of the biochemical composition of normal bronchial tissue is a prerequisite for understanding the biochemical changes that accompany histological changes during lung cancer development. In this study, 12 Raman microspectroscopic mapping experiments are performed on frozen sections of normal bronchial tissue. Pseudocolor Raman images are constructed using principal component analysis and K-means cluster analysis. Subsequent comparison of Raman images with histologic evaluation of stained sections enables the identification of the morphologic origin (e.g., bronchial mucus, epithelium, fibrocollagenous stroma, smooth muscle, glandular tissue, and cartilage) of the spectral features. Raman spectra collected from the basal side of epithelium consistently show higher DNA contributions and lower lipid contributions when compared with superficial epithelium spectra. Spectra of bronchial mucus reveal a strong signal contribution of lipids, predominantly triolein. These spectra are almost identical to the spectra obtained from submucosal glands, which suggests that the bronchial mucus is mainly composed of gland secretions. Different parts of fibrocollagenous tissue are distinguished by differences in spectral contributions from collagen and actin/myosin. Cartilage is identified by spectral contributions of glycosaminoglycans and collagen. As demonstrated here, in situ analysis of the molecular composition of histologic structures by Raman microspectroscopic mapping creates powerful opportunities for increasing our fundamental understanding of tissue organization and function. Moreover, it provides a firm basis for further in vitro and in vivo investigations of the biochemical changes that accompany pathologic transformation of tissue.

Long term prognostic value of myocardial viability and ischaemia during dobutamine stress echocardiography in patients with ischaemic cardiomyopathy undergoing coronary revascularisation

Objective: To evaluate the relative merits of viability and ischaemia for prognosis after revascularisation. Methods: Low–high dose dobutamine stress echocardiography (DSE) was performed before revascularisation in 128 consecutive patients with ischaemic cardiomyopathy (mean (SD) left ventricular ejection fraction (LVEF) 31 (8)%). Viability (defined as contractile reserve (CR)) and ischaemia were assessed during low and high dose dobutamine infusion, respectively. Cardiac death was evaluated during a five year follow up. Clinical, angiographic, and echocardiographic data were analysed to identify predictors of events. Results: Univariable predictors of cardiac death were the presence of multivessel disease (hazard ratio (HR) 0.21, p < 0.001), baseline LVEF (HR 0.90, p < 0.0001), wall motion score index (WMSI) at rest (HR 4.02, p u200a=u200a 0.0006), low dose DSE (HR 7.01, p < 0.0001), peak dose DSE (HR 4.62, p < 0.0001), the extent of scar (HR 1.39, p < 0.0001), and the presence of CR in ⩾ 25% of dysfunctional segments (HR 0.34, p u200a=u200a 0.02). The best multivariable model to predict cardiac death included the presence of multivessel disease, WMSI at low dose DSE, and the presence of CR in ⩾ 25% of the severely dysfunctional segments (HR 9.62, p < 0.0001). Inclusion of ischaemia in the model did not provide additional predictive value. Conclusion: The findings of the present study illustrate that in patients with ischaemic cardiomyopathy, the extent of viability (CR) is a strong predictor of long term prognosis after revascularisation. Ischaemia did not add significantly in predicting outcome.

Opposite Patterns of Left Ventricular Remodeling After Coronary Revascularization in Patients With Ischemic Cardiomyopathy: Role of Myocardial Viability

Background—In patients with ischemic cardiomyopathy, left ventricular (LV) remodeling is an important prognostic indicator. The precise relation between viable myocardium, revascularization, and ongoing or reversed remodeling is unknown and was evaluated in the present study. Methods and Results—A total of 100 patients with ischemic cardiomyopathy underwent dobutamine stress echocardiography to assess myocardial viability and LV geometry (volumes and shape). At a mean of 10.2 months and 4.5 years after revascularization, resting echocardiography was repeated to evaluate LV remodeling. Long-term follow-up (mean 5±2 years) data were obtained. According to dobutamine stress echocardiography, 44 patients (44%) were defined as viable (≥4 viable segments) and 56 as nonviable. After revascularization, 40 patients (43%) had ongoing LV remodeling and 53 (57%) did not (in 7 patients who died early after revascularization, postoperative echocardiographic evaluation was not available). On multivariable analysis, the number of viable segments was the only predictor of ongoing LV remodeling (OR 0.60, 95% CI 0.48 to 0.75; P<0.0001). The likelihood of LV remodeling decreased as the number of viable segments increased. During the follow-up, reverse remodeling was present in viable patients, whereas in nonviable patients, LV volumes significantly increased, which indicates ongoing LV remodeling. At follow-up, viable patients also showed a persistent improvement of heart failure symptoms and fewer cardiac events than nonviable patients (P<0.05). Conclusions—In patients with ischemic cardiomyopathy, a substantial amount of viable myocardium prevents ongoing LV remodeling after revascularization and is associated with persistent improvement of symptoms and better outcome.