Tomislav Mihaljevic

Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping

The use of near-infrared or infrared photons is a promising approach for biomedical imaging in living tissue. This technology often requires exogenous contrast agents with combinations of hydrodynamic diameter, absorption, quantum yield and stability that are not possible with conventional organic fluorophores. Here we show that the fluorescence emission of type II quantum dots can be tuned into the near infrared while preserving absorption cross-section, and that a polydentate phosphine coating renders them soluble, disperse and stable in serum. We then demonstrate that these quantum dots allow a major cancer surgery, sentinel lymph node mapping, to be performed in large animals under complete image guidance. Injection of only 400 pmol of near-infrared quantum dots permits sentinel lymph nodes 1 cm deep to be imaged easily in real time using excitation fluence rates of only 5 mW/cm2. Taken together, the chemical, optical and in vivo data presented in this study demonstrate the potential of near-infrared quantum dots for biomedical imaging.

Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting

Objective:Our objective was to quantify incremental risk associated with transfusion of packed red blood cells and other blood components on morbidity after coronary artery bypass grafting. Design:The study design was an observational cohort study. Setting:This investigation took place at a large tertiary care referral center. Patients:A total of 11,963 patients who underwent isolated coronary artery bypass from January 1, 1995, through July 1, 2002. Interventions:None. Measurements and Main Results:Among the 11,963 patients who underwent isolated coronary artery bypass grafting, 5,814 (48.6%) were transfused. Risk-adjusted probability of developing in-hospital mortality and morbidity as a function of red blood cell and blood-component transfusion was modeled using logistic regression. Transfusion of red blood cells was associated with a risk-adjusted increased risk for every postoperative morbid event: mortality (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.67–1.87; p < .0001), renal failure (OR, 2.06; 95% CI, 1.87–2.27; p < .0001), prolonged ventilatory support (OR, 1.79; 95% CI, 1.72–1.86; p < .0001), serious infection (OR, 1.76; 95% CI, 1.68–1.84; p < .0001), cardiac complications (OR, 1.55; 95% CI, 1.47–1.63; p < .0001), and neurologic events (OR, 1.37; 95% CI, 1.30–1.44; p < .0001). Conclusions:Perioperative red blood cell transfusion is the single factor most reliably associated with increased risk of postoperative morbid events after isolated coronary artery bypass grafting. Each unit of red cells transfused is associated with incrementally increased risk for adverse outcome.

One thousand minimally invasive valve operations: early and late results.

Objective:We sought to evaluate the potential benefits of minimally invasive approaches for treatment of isolated aortic and mitral valve disease. Methods:From 7/96 to 04/03, we performed 1000 minimally invasive valve operations: 526 aortic (AV) procedures (64 years; mean, 25–95) and 474 mitral (MV) procedures (58 years; mean, 17–90). Results:In the AV group, an upper ministernotomy was used in 492/526 patients (93%) and a right parasternal approach in 34 (7%). Sixty-three patients had reoperative aortic valve replacements. In the MV group lower sternotomy was used in 260/474 (55%), right parasternal in 200/474 (42%), and a right thoracotomy in 14 patients. MV repair was performed in 416 and MV replacement in 58 patients. Operative mortality was 12/526 (2%) in the AV and 1/474 (0.2%) in the MV group. Freedom from reoperation at 6 years was 99% and 95% in the AV and MV group, respectively. Late mortality was 5% in the AV and 3% in the MV group, respectively. Conclusions:Minimally invasive valve surgery can be performed at very low levels of morbidity and mortality, with results equal to or better than conventional techniques. All forms of valve repair and replacement operations can be performed. Long-term survival and freedom from reoperation are excellent.

Survival after valve replacement for aortic stenosis: Implications for decision making

OBJECTIVE Recommendations for aortic valve replacement in severe aortic stenosis are based primarily on the presence of symptoms. However, the onset of symptoms is often insidious, potentially leading to delayed intervention and suboptimal results. Identifying factors that reduce the survival of patients undergoing aortic valve replacement could lead to revised treatment guidelines and improved outcomes. METHODS We conducted a single-center observational clinical study of 3049 patients with aortic stenosis who underwent native aortic valve replacement with a single type of bioprosthesis. The primary end point was all-cause mortality from the date of operation. Multivariable analysis of risk factors for death was performed in the multiphase hazard function domain. RESULTS The presence of severe left ventricular hypertrophy at operation, which preceded symptoms in 17% of patients, was associated with decreased survival. This effect was magnified by the severity of aortic stenosis (P = .02) and use of small prostheses (P = .01). The presence of left ventricular dysfunction reduced survival (P = .0003). Although older age was a risk factor for death (P < .0001), elderly patients had survival comparable to their age, race, and sex-matched cohorts, whereas younger patients had worse than expected survival that was further diminished with insertion of a small prosthesis (P = .01). CONCLUSION To optimize survival, earlier aortic valve replacement should be considered even in asymptomatic patients before severe left ventricular hypertrophy or dysfunction develops. In younger patients, the largest possible prosthesis should be implanted to minimize residual gradient; in elderly patients, complex operations just to insert larger prostheses should be avoided.

Robotic repair of posterior mitral valve prolapse versus conventional approaches: potential realized.

OBJECTIVE Robotic mitral valve repair is the least invasive approach to mitral valve repair, yet there are few data comparing its outcomes with those of conventional approaches. Therefore, we compared outcomes of robotic mitral valve repair with those of complete sternotomy, partial sternotomy, and right mini-anterolateral thoracotomy. METHODS From January 2006 to January 2009, 759 patients with degenerative mitral valve disease and posterior leaflet prolapse underwent primary isolated mitral valve surgery by complete sternotomy (n = 114), partial sternotomy (n = 270), right mini-anterolateral thoracotomy (n = 114), or a robotic approach (n = 261). Outcomes were compared on an intent-to-treat basis using propensity-score matching. RESULTS Mitral valve repair was achieved in all patients except 1 patient in the complete sternotomy group. In matched groups, median cardiopulmonary bypass time was 42 minutes longer for robotic than complete sternotomy, 39 minutes longer than partial sternotomy, and 11 minutes longer than right mini-anterolateral thoracotomy (P < .0001); median myocardial ischemic time was 26 minutes longer than complete sternotomy and partial sternotomy, and 16 minutes longer than right mini-anterolateral thoracotomy (P < .0001). Quality of mitral valve repair was similar among matched groups (P = .6, .2, and .1, respectively). There were no in-hospital deaths. Neurologic, pulmonary, and renal complications were similar among groups (P > .1). The robotic group had the lowest occurrences of atrial fibrillation and pleural effusion, contributing to the shortest hospital stay (median 4.2 days), 1.0, 1.6, and 0.9 days shorter than for complete sternotomy, partial sternotomy, and right mini-anterolateral thoracotomy (all P < .001), respectively. CONCLUSIONS Robotic repair of posterior mitral valve leaflet prolapse is as safe and effective as conventional approaches. Technical complexity and longer operative times for robotic repair are compensated for by lesser invasiveness and shorter hospital stay.

Minimally invasive versus conventional mitral valve surgery: A propensity-matched comparison

OBJECTIVE Less invasive approaches to mitral valve surgery are increasingly used for improved cosmesis; however, few studies have investigated their effect on outcome. We sought to compare these minimally invasive approaches fairly with conventional full sternotomy by using propensity-matching methods. METHODS From January 1995 to January 2004, 2124 patients underwent isolated mitral valve surgery through a minimally invasive approach, and 1047 underwent isolated mitral valve surgery through a conventional sternotomy. Because there were important differences in patient characteristics, a propensity score based on 42 factors was used to obtain 590 well-matched patient pairs (56% of cases). RESULTS In-hospital mortality was similar for propensity-matched patients: 0.17% (1/590) for those undergoing minimally invasive surgery and 0.85% (5/590) for those undergoing conventional surgery (P = .2). Occurrences of stroke (P = .8), renal failure (P > .9), myocardial infarction (P = .7), and infection (P = .8) were also similar. However, 24-hour mediastinal drainage was less after minimally invasive surgery (median, 250 vs 350 mL; P < .0001), and fewer patients received transfusions (30% vs 37%, P = .01). More patients undergoing minimally invasive surgery were extubated in the operating room (18% vs 5.7%, P < .0001), and postoperative forced expiratory volume in 1 second was higher. Early after operation, pain scores were lower (P < .0001) after minimally invasive surgery. CONCLUSION Within that portion of the spectrum of mitral valve surgery in which propensity matching was possible, minimally invasive mitral valve surgery had cosmetic, blood product use, respiratory, and pain advantages over conventional surgery, and no apparent detriments. Mortality and morbidity for robotic and percutaneous procedures should be compared with these minimally invasive outcomes.

The influence of leukocyte filtration during cardiopulmonary bypass on postoperative lung function. A clinical study.

The accumulation of activated leukocytes in the pulmonary circulation plays an important role in the pathogenesis of lung dysfunction associated with cardiopulmonary bypass. Animal studies have demonstrated that the elimination of leukocytes from the circulation reduces postoperative lung injury and improves postoperative pulmonary function. We conducted a prospective randomized clinical study to evaluate whether postoperative lung function could be improved by use of a leukocyte filter during cardiopulmonary bypass. Elective coronary artery bypass grafting was done with a leukocyte-depleting arterial blood filter incorporated in the extracorporeal circuit (14 patients, leukocyte filter group) or without the filter (18 patients, control group). Blood samples collected at intervals before, during, and after operation were used for analysis of blood cell counts, elastase concentrations, and arterial blood gases. The use of the leukocyte filter caused no significant reduction in leukocyte count (p = 0.86). There were no differences in postoperative lung function between the groups, as assessed through (1) oxygenation index (290 for leukocyte filter group compared with 329 for control group, 95% confidence interval, 286 to 372, p = 0.21), (2) pulmonary vascular resistance (p = 0.10), and (3) intubation time (16.6 hours for leukocyte filter group versus 15.7 hours for control group, 95% confidence interval, 12.1 to 19.1 hours, p = 0.72). The levels of neutrophil elastase were significantly higher at the end of cardiopulmonary bypass in the leukocyte filter group (460 microgram/L in leukocyte filter group versus 230 microgram/L in control group, 95% confidence interval, 101 to 359 microgram/L, p = 0.003). We conclude that the clinical use of the present form of leukocyte-depleting filter did not improve any of the postoperative lung function parameters analyzed in this study.

Bicuspid aortic valve surgery with proactive ascending aorta repair.

OBJECTIVES Bicuspid aortic valves are associated with aortic catastrophes, particularly dissection. We examined whether proactive repair of associated dilatation would reduce risk of subsequent aortic dissection or reoperation and whether more aggressive resection is needed in patients undergoing bicuspid aortic valve surgery alone. METHODS From January 1993 to June 2003, 1989 patients (of our total experience of 4316) underwent bicuspid aortic valve surgery. Long-term outcomes of 1810 were analyzed according to aortic size and whether bicuspid aortic valve surgery was performed alone or with aortic repair. RESULTS In-hospital 30-day survival was similar (98.8% valve alone vs 98.9% with aortic repair), with no penalty incurred for concomitant aortic repair. Bicuspid aortic valve-alone patients had worse late survival (75% vs 85% at 10 years, P = .0001), but in the matched cohort survival was nearly identical (85% vs 86%; P = .7). With this strategy, freedom from late aortic events was high in both groups (99% valve alone vs 97% with aortic repair at 10 years; P[log-rank] = .06) and similar in the matched cohort (95% vs 97%; P = .2). Approximately 95% of patients undergoing valve-alone surgery had aortic diameters smaller than 4.6 cm or cross-sectional area/height ratios less than 9.4 cm(2)/m; 80% undergoing valve surgery plus aortic repair had diameters larger than 4.1 cm or ratios greater than 7.3 cm(2)/m. Only 0.2% of events occurred at an aortic diameter size of less than 4.5 cm. CONCLUSIONS Aortic size larger than 4.5 cm or aortic cross-sectional area/height ratio greater than 8 to 10 should be considered triggers for concurrent aortic repair, because there is no added risk, and late survival is better; however, more aggressive resection is unwarranted.

Influence of Concentric Left Ventricular Remodeling on Early Mortality After Aortic Valve Replacement

BACKGROUND Severe left ventricular (LV) hypertrophy increases risk for adverse outcome after aortic valve replacement. Whether LV geometry influences mortality risk after aortic valve replacement is unclear. And, whether LV mass or relative wall thickness (RWT) better predicts risk for adverse postoperative outcomes is unknown. The purpose of this investigation was to examine the influence of LV geometry and LV hypertrophy on morbidity and in-hospital mortality after aortic valve replacement, and to determine whether LV mass or RWT had better prognostic ability. METHODS Between January 1996 and June 2004, 5,083 patients underwent aortic valve replacement. Preoperative echocardiographic data was used to calculate LV mass and RWT. Left ventricular geometry was classified into one of four categories on the basis of LV mass indexed to body height and RWT: (1) concentric hypertrophy, (2) eccentric hypertrophy, (3) concentric remodeling, and (4) normal. Postoperative mortality and multisystem morbidities of patients with concentric geometries were compared to patients with nonconcentric geometries by propensity and logistic regression modeling. Also, prognostic ability of RWT and LV mass was compared. RESULTS Nine hundred sixty-four patients with concentric geometry were propensity-matched to 964 patients with nonconcentric geometry. In-hospital mortality (38 [3.9%] versus 18 [1.9%]; p = 0.007), cardiac morbidity (33 [3.4%] versus 17 [1.8%]; p = 0.022), and prolonged intubation (85 [8.8%] versus 58 [6.0%]; p = 0.019) were higher in patients with concentric versus nonconcentric geometry. Increasing RWT, not LV mass, was associated with adverse outcomes. CONCLUSIONS Concentric geometries are associated with increased risk for in-hospital mortality after aortic valve replacement. Increased RWT is associated with adverse outcomes. Preoperative risk stratification should include assessments of LV hypertrophy and LV geometry.

Should Patients With Severe Degenerative Mitral Regurgitation Delay Surgery Until Symptoms Develop

BACKGROUND The American College of Cardiology/American Heart Association practice guidelines recommending surgery for asymptomatic patients with severe mitral regurgitation caused by degenerative disease remain controversial. This study examined whether delaying surgery until symptoms occur causes adverse cardiac changes and jeopardizes outcome. METHODS From January 1985 to January 2008, 4,586 patients had primary isolated mitral valve surgery for degenerative mitral regurgitation; 4,253 (93%) underwent repair. Preoperatively, 30% were in New York Heart Association (NYHA) class I (asymptomatic), 56% in class II, 13% in class III, and 2% in class IV. Multivariable analysis and propensity matching were used to assess association of symptoms (NYHA class) with cardiac structure and function and postoperative outcomes. RESULTS Increasing NYHA class was associated with progressive reduction in left ventricular function, left atrial enlargement, and development of atrial fibrillation and tricuspid regurgitation. These findings were evident even in class II patients (mild symptoms). Repair was accomplished in 96% of asymptomatic patients, and in progressively fewer as NYHA class increased (93%, 86%, and 85% in classes II to IV, respectively; p < 0.0001). Hospital mortality was 0.37%, but was particularly high in class IV (0.29%, 0.20%, 0.67%, and 5.1% for classes I to IV, respectively; p = 0.004). Although long-term survival progressively diminished with increasing NHYA class, these differences were largely related to differences in left ventricular function and increased comorbidity. CONCLUSIONS In patients with severe degenerative mitral regurgitation, the development of even mild symptoms by the time of surgical referral is associated with deleterious changes in cardiac structure and function. Therefore, particularly because successful repair is highly likely, early surgery is justified in asymptomatic patients with degenerative disease and severe mitral regurgitation.