Joan Ivanov

Cardiomyocyte Transplantation Improves Heart Function

BACKGROUND Transplantation of cultured cardiomyocytes into myocardial scar tissue may prevent heart failure. METHODS Scar tissue was produced in the left ventricular free wall of 15 rats (weight, 450 g) by cryoinjury. Seven animals had operation only and survived for 8 weeks (sham group). Four weeks after cryoinjury, cultured fetal rat cardiomyocytes or culture medium was injected into the scar tissue of transplantation (n = 5) and control (n = 5) animals, respectively. Five other rats were sacrificed for scar assessment. Eight weeks after cryoinjury heart function in the transplantation, control, and sham groups was measured using a Langendorff preparation. Histologic studies were performed to quantify the extent of the scar and the transplanted cells. RESULTS Four weeks after cryoinjury, 36% +/- 4% (mean +/- 1 standard error) of the left ventricular free wall surface area was scar tissue. At 8 weeks, the scar size had increased (p < 0.01) to 55% +/- 3% in the control group. Although the scar size (43% +/- 2%) in the transplantation group at 8 weeks was not significantly different from that at 4 weeks, it was less (p < 0.05) than that in the control group. Hearts in the sham group had no scar tissue. The transplanted cardiomyocytes had formed cardiac tissue within the myocardial scar. Systolic and developed pressures in the transplantation group hearts were greater (p = 0.0001) than in the control group hearts but less (p < 0.01) than those in the sham group hearts. CONCLUSIONS The transplanted cardiomyocytes formed cardiac tissue in the myocardial scar, limited scar expansion, and improved heart function compared with findings in the control hearts.

Deep Sternal Wound Infection: Risk Factors and Outcomes

BACKGROUND Deep sternal wound infection (DSWI) is a serious complication of cardiac operations performed by median sternotomy. We attempted to define the predictors of DSWI and to describe the outcomes of two treatment strategies used at our institution. METHODS Retrospective review was performed using prospectively gathered data on 12,267 consecutive cardiac surgical patients from 1990 to 1995. Chart review was performed on all patients in whom DSWI developed, and follow-up was obtained on 100% of these patients. RESULTS Deep sternal wound infections developed in 92 patients (incidence 0.75%). Multivariable predictors for development of DSWI in all patients were (odds ratios and 95% confidence intervals in parentheses) (1) diabetes mellitus (2.6; 1.7 to 4.0) and (2) male sex (2.2; 1.3 to 3.9). In patients receiving coronary artery bypass grafting alone, independent predictors were (1) bilateral internal thoracic artery grafts (3.2; 1.1 to 8.9), (2) diabetes (2.7; 1.6 to 4.3), and (3) male sex (1.8; 0.9 to 3.7). For all other patients, predictors were (1) age more than 74 years (3.3; 1.1 to 10.1), (2) male sex (3.0; 1.1 to 8.1), and (3) diabetes (2.3; 0.9 to 5.8). Bilateral internal thoracic artery grafts increased the risk of DSWI in all subgroups of coronary artery bypass graft patients, particularly in diabetics who had a 14.3% incidence of DSWI after bilateral internal thoracic artery grafting. Patients with DSWIs received either sternal debridement with primary closure (n=45) or sternectomy with flap reconstruction (n=46). The 6-month freedom from adverse event rate (ie, readmission, reoperation, or death) was 76% for both groups of patients. CONCLUSIONS Male sex and diabetes are predictors of DSWI in all cardiac surgical patients. Bilateral internal thoracic artery grafting may be contraindicated in diabetic patients.

Dilation of the pulmonary autograft after the ross procedure

OBJECTIVE Dilation of pulmonary autograft after the Ross procedure is being recognized with increasing frequency. This study was undertaken to examine the extent of this problem and factors that may be associated with it. METHODS The clinical, operative, and echocardiographic data of 118 patients who underwent the Ross procedure were reviewed. The mean age of 79 men and 39 women was 34 +/- 9 years, range 17 to 57 years. Bicuspid or other congenital aortic valve disease was present in 81% of patients. The pulmonary autograft was sutured as a valve in the subcoronary position in 2 patients, as a root inside of the aortic root in 45, and was used for complete aortic root replacement in 71. Teflon felt was not used to buttress the proximal or the distal anastomosis of the pulmonary autograft. The diameters of the sinuses of Valsalva, aortic anulus, and sinotubular junction were measured early and late after the operation with echocardiography. The mean follow-up was 44 months. RESULTS The diameter of the sinuses of Valsalva increased from 31.4 +/- 0.4 mm to 33.7 +/- 0.5 mm (P =.01). Analysis of covariance revealed a significant change over time in this diameter, as well as a difference between operative techniques, with replacement of the aortic root being associated with a higher risk of dilation (P =. 0006). In 13 patients the diameter ranged from 40 to 51 mm. The diameter of the aortic anulus decreased in most patients and increased in 15, but there was no interaction between these changes and the operative technique. The diameter of the sinotubular junction increased in patients who had aortic root replacement and decreased in patients who had aortic root inclusion (P =.007). Moderate aortic insufficiency developed in 7 patients, and 3 required replacement of the pulmonary autograft. All patients with moderate aortic insufficiency had dilation of the aortic anulus and/or sinotubular junction. CONCLUSIONS Dilation of the pulmonary autograft after the Ross procedure may occur because of an intrinsic abnormality of the pulmonary root in patients with congenital aortic valve disease. The technique of aortic root replacement is associated with a higher risk of dilation of the sinuses of Valsalva and sinotubular junction than the technique of aortic root inclusion.

Predictors of low cardiac output syndrome after coronary artery bypass

The purpose of this study was to identify patients at risk for the development of low cardiac output syndrome after coronary artery bypass. Low cardiac output syndrome was defined as the need for postoperative intraaortic balloon pump or inotropic support for longer than 30 minutes in the intensive care unit to maintain the systolic blood pressure greater than 90 mm Hg and the cardiac index greater than 2.2 L/min per square meter. The preoperative patient characteristics that were independent predictors of low cardiac output syndrome were identified among 4558 consecutive patients who underwent isolated coronary artery bypass at The Toronto Hospital between July 1, 1990, and December 31, 1993. The overall prevalence of low cardiac output syndrome was 9.1% (n = 412). The operative mortality rate was higher in patients in whom low cardiac output syndrome developed than in those in whom it did not develop (16.9% versus 0.9%, p < 0.001). Stepwise logistic regression analyses identified nine independent predictors of low output syndrome (percent frequency in parentheses) and calculated the factor-adjusted odds ratios associated with each predictor: (1) left ventricular ejection fraction less than 20% (27%, odds ratio 5.7); (2) repeat operation (25%, odds ratio 4.4); (3) emergency operation (27%, odds ratio 3.7); (4) female gender (16%, odds ratio 2.5); (5) diabetes (13%, odds ratio 1.6); (6) age older than 70 years (13%, odds ratio 1.5); (7) left main coronary artery stenosis (12%, odds ratio 1.4); (8) recent myocardial infarction (16%, odds ratio 1.4); and (9) triple-vessel disease (10%, odds ratio 1.3). Low cardiac output syndrome is a clinical outcome that may result from inadequate myocardial protection or perioperative ischemic injury. Patients at high risk for the development of low cardiac output syndrome should be the focus of trials of new techniques of myocardial protection to resuscitate the ischemic myocardium.

Long-term results of mitral valve repair for myxomatous disease with and without chordal replacement with expanded polytetrafluoroethylene sutures ☆ ☆☆ ★ ★★ ♢

OBJECTIVE This study was carried out to evaluate the long-term results of mitral valve repair for mitral regurgitation caused by myxomatous disease of the mitral valve and the late effects of chordal replacement with expanded polytetrafluoroethylene sutures in this operation. METHODS A total of 324 patients with mitral regurgitation caused by myxomatous disease underwent mitral valve repair from 1981 to 1995; the group comprised 241 men and 83 women whose mean age was 58 +/- 14 years. Chordal replacement with expanded polytetrafluoroethylene sutures has been performed in 165 patients since 1985. Most of the patients who had chordal replacement with expanded polytetrafluoroethylene sutures had prolapse of the anterior leaflet or prolapse of both leaflets, whereas most patients who had mitral valve repair without chordal replacement had prolapse of the posterior leaflet. Patients were followed up at annual intervals and had a Doppler echocardiographic study. The follow-up was complete and extended from 6 to 156 months (mean 36 +/- 30 months). RESULTS Two operative and 21 late deaths occurred (14 cardiac and 7 noncardiac). At 10 years the actuarial survival was 75% +/- 5%, the freedom from stroke was 94% +/- 2%, the freedom from transient ischemic attacks was 92% +/- 4%, the freedom from endocarditis was 99% +/- 1%, the freedom from mitral valve reoperation was 96% +/- 1%, and the freedom from severe mitral regurgitation was 93% +/- 3%. Chordal replacement with expanded polytetrafluoroethylene sutures had no effect on any of these end points. CONCLUSIONS Mitral valve repair was feasible in most patients with mitral regurgitation caused by myxomatous disease and it was associated with low rates of valve-related complications. Chordal replacement with expanded polytetrafluoroethylene had no adverse effect on the late outcome and was believed to have increased the probability of mitral valve repair.

Ready-made, recalibrated, or Remodeled? Issues in the use of risk indexes for assessing mortality after coronary artery bypass graft surgery.

BACKGROUND Risk indexes for operative mortality after cardiac surgery are used for comparative profiling of surgeons or centers. We examined whether clinicians and managers should use an existing index without modification, recalibrate it for their populations, or derive a new model altogether. METHODS AND RESULTS Drawing on 7491 consecutive patients who underwent isolated CABG at 2 Toronto teaching hospitals between 1993 and 1996, we compared 3 strategies: (1) using a ready-made model originally derived and validated in our jurisdiction; (2) recalibrating the ready-made model to better fit the population; and (3) deriving a new model with additional risk factors. We assessed statistical accuracy, ie, area under a receiver-operator characteristic curve (ROC); precision, ie, statistical goodness-of-fit; and actual impact on both risk-adjusted operative mortalities (RAOM) and performance rankings for 14 surgeons. The new model was slightly more accurate than the ready-made model (ROC, 0.78 versus 0.76; P<0.05), albeit not different from the recalibrated model (ROC, 0.77). The ready-made model showed poor fit between the predicted and observed results (P<0.001), leading to significant underestimation of RAOM (1.6+/-0. 2%) compared with the other strategies (2.5+/-0.2%; P=0.048). Remodeling also changed the performance rankings among half the surgeons with higher RAOM. CONCLUSIONS Poorly calibrated risk algorithms can bias the calculation of RAOM and alter the results of surgeon-specific profiles. Any existing index used for risk assessment in cardiac surgery should be episodically recalibrated or compared with new models derived from local subjects to ensure that its performance remains optimal.

Fifteen-Year Trends in Risk Severity and Operative Mortality in Elderly Patients Undergoing Coronary Artery Bypass Graft Surgery

BACKGROUND Trends in risk-severity and operative mortality (OM) were examined in 3330 consecutive patients aged 70 years and older who underwent isolated coronary artery bypass graft surgery (CABG) between 1982 and 1996. METHODS AND RESULTS The proportion of elderly patients rose significantly over time (P<.001). Crude OM among the elderly was 7.2% in 1982 to 1986, fell to 4.4% in 1987 to 1991, but did not improve thereafter. Logistic regression analysis of OM was used to construct relative risk groups (low, medium, or high). The prevalence of high-risk elderly patients rose significantly over time (P=.001) from 16.2% in 1982 to 1986 to 19.5% in 1987 to 1991 and 26.9% in 1992 to 1996. OM in high-risk patients fell significantly (P=.044) from 17.2% in 1982 to 1986 to 9.1% in 1987 to 1991 and was 8.9% in 1992 to 1996. Contemporary independent predictors of OM among elderly patients were poor ventricular function (LV grade 2 to 3, odds ratio [OR], 2.6; 95% confidence interval [CI], 1.3 to 5.2; and LV grade 4, OR, 10.7; 95% CI, 4.4 to 26); previous CABG (OR, 3.7; 95% CI, 2.0 to 7.0), female sex (OR, 1.8; 95% CI, 1.1 to 2.8), peripheral vascular disease (OR, 1.8; 95% CI, 1.1 to 2.8), and diabetes (OR, 1.7; 95% CI, 1.1 to 2.7). Previous angioplasty was protective (OR, 0.3; 95% CI, 0.1 to 0.9). CONCLUSIONS OM in elderly patients has declined significantly in recent years despite an increase in the prevalence and severity of their risk factors. A careful weighing of risk, rather than advanced age alone, should determine who is offered surgical revascularization. In this regard, poor ventricular function and repeat CABG continue to have the greatest impact on OM in elderly patients.

Risk factors for stroke in patients undergoing coronary artery bypass grafting

OBJECTIVE To determine predictors of stroke in patients undergoing first-time coronary bypass grafting, we prospectively collected data on 1631 consecutive patients. METHODS Patients with a history of stroke and/or central nervous system symptoms (n = 134) and/or carotid bruits (n = 95) underwent carotid Doppler evaluation. Stenosis greater than 70% was considered significant. Patients with symptomatic disease or asymptomatic bilateral disease were referred for combined coronary bypass and carotid endarterectomy (n = 21). Patients with neurologic symptoms after the operation were assessed by a neurologist and underwent a computed tomographic scan. Events were classified as reversible transient ischemic attack, reversible ischemic neurologic deficit, or irreversible stroke. RESULTS There were 19 strokes (1.2%) and 20 deaths (1.2%) in this series. In patients with carotid screening, risk of stroke increased with severity of carotid disease and ranged from 0% in patients without stenosis, to 3.2% (1/31) in those with greater than 70% stenosis, and to 27.3% (6/22) in those with carotid occlusion. By stepwise logistic regression analysis six variables were identified as risk factors for stroke. The most important predictor was carotid occlusion with or without contralateral stenosis (odds ratio = 28, 95% confidence interval (8,105). In this group, four of five strokes occurred on the occluded side. Other risk factors were presence of ascending aortic disease at the time of surgery (odds ratio = 12.8, confidence interval 3,48), perioperative myocardial infarction (odds ratio = 8.2, confidence interval 2,33), poor left ventricular function (odds ratio = 4.6, confidence interval 1,19), peripheral vascular disease (odds ratio = 3.2, confidence interval 1,9), and age > 60 years (odds ratio = 2.9, confidence interval 0.8,11). CONCLUSION We conclude that risk factors for perioperative stroke in patients undergoing coronary artery bypass grafting are multiple. Carotid scanning in patients with neurologic symptoms or carotid bruits can identify patients at increased risk. Patients with carotid occlusion are at high risk for stroke on the occluded side.

Aortic valve-sparing operations in patients with aneurysms of the aortic root or ascending aorta.

BACKGROUND Aortic valve-sparing operations are an alternative to aortic root replacement in patients with aortic root aneurysms, or aortic valve replacement and supracoronary replacement of the ascending aorta in patients with ascending aorta aneurysms and dilated sinotubular junctions with consequent aortic insufficiency. METHODS From 1988 to 2001, 230 patients underwent aortic valve-sparing operations for aortic root aneurysms (151 patients) or ascending aortic aneurysms with aortic insufficiency (79 patients). Two types of aortic valve-sparing operations were performed in patients with aortic root aneurysms: reimplantation of the aortic valve and remodeling of the aortic root. Mean follow-up was 3.8 +/- 2.8 years. RESULTS Patients with aortic root aneurysms were younger, had less severe aortic insufficiency, less extensive vascular disease, and better left ventricular function than patients with ascending aorta aneurysms. The 8-year survival was 83% +/- 5% for the first group and 36% +/- 14% for the second. The freedom from aortic valve reoperation at 8 years was 99% +/- 1% for the first group and 97% +/- 2% for the second. In patients who had aortic root aneurysms, 3 developed severe aortic insufficiency (AI), and 15 developed moderate AI, for an 8-year freedom from significant AI of 67% +/- 7%. But freedom from AI was 90% +/- 3% after the technique of reimplantation, and 55% +/- 6% after the technique of remodeling (p = 0.02). In patients with ascending aortic aneurysms, the freedom from AI greater than 2+ at 8 years was 67% +/- 11%. CONCLUSIONS The long-term results of aortic valve sparing for aortic root aneurysms are excellent, and reimplantation of the aortic valve may provide a more stable repair of the aortic valve than remodeling of the aortic root.

Aortic valve replacement with stentless and stented porcine valves: a case-match study

OBJECTIVES To assess the potential benefits of the hemodynamic superiority of stentless valves, we conducted a case-match study among patients who underwent aortic valve replacement with two types of porcine bioprostheses: the Toronto SPV and the stented Hancock II bioprosthesis. METHODS Preoperative clinical variables predictive of death after aortic valve replacement were determined by a stepwise logistic regression analysis in a series of 908 consecutive patients who received porcine aortic bioprostheses during a 14-year interval. Advanced age, New York Heart Association functional class IV, left ventricular ejection fraction of less than 30%, and coronary artery disease were independent predictors of death. On the basis of these four variables, 198 pairs of patients who survived aortic valve replacement with stentless and stented porcine valves were matched. The follow-up, truncated to the shortest interval for each matched pair, was 43 +/- 24 months for both groups. RESULTS At 8 years the actuarial survival was 91% +/- 4% for the Toronto SPV group and 69% +/- 8% for the Hancock II group (p = 0.006); the freedom from cardiac-related death was 95% +/- 4% for the Toronto SPV and 81% +/- 8% for the Hancock II (p = 0.01); the freedom from any valve-related complication was 81% +/- 5% for the Toronto SPV and 50% +/- 10% for the Hancock II (p = 0.008). A Cox proportional hazard model demonstrated a significant reduction in cardiac mortality rates and valve-related morbidity in patients who received the Toronto SPV bioprosthesis. CONCLUSIONS Although it is possible that confounding factors may have played a role in the clinical outcomes of this case-control study, the study suggests that aortic valve replacement with a stentless porcine valve enhances survival. This is believed to be due to the hemodynamic superiority of these valves.