Acceptability and psychometric properties of the Minnesota Living With Heart Failure Questionnaire among patients undergoing heart valve surgery: validation and comparison with SF-36.

BACKGROUND: Health-related quality of life (HQOL) enhancement is a major objective of valvular surgery (VS), but assessments have been limited primarily to generic measures that may not be optimally responsive to intervention. Disease-specific instruments have been used in heart failure (HF), commonly associated with valve disease, but have been neither validated nor routinely applied among patients undergoing VS. METHODS AND RESULTS: We administered the Minnesota Living with Heart Failure (MLHFQ) and SF-36 questionnaires preoperatively (T(0)) to 50 patients undergoing VS and at 1 (T(1)) and 6 months (T(2)) after VS. Performance of MLHFQ was evaluated and compared with SF-36. MLHFQ completion rates were >98% (NS vs. SF-36); Cronbach's alpha was > or = 0.9 (total score, dimensions), supporting internal reliability. Confirmatory factor analysis verified good model fit for physical/emotional domain items (relative chi-squares < 3.0, critical ratios > 2.0, both instruments), supporting structural validity. Spearman coefficients correlating MLHFQ with parallel SF-36 domains were moderate to high (0.6-0.9; P < or = .001: T(0)-T(2)), supporting convergent validity. Baseline HQOL was poorest in patients with HF (P < or = .05 [both instruments]), supporting criterion validity. Responsiveness (proportional HQOL change scores: T(0) vs. T(2)) to VS was greater with MLHFQ vs. SF-36 (P < or = .002). CONCLUSIONS: Among patients undergoing VS, the MLHFQ is highly acceptable and maintains good psychometric properties, comparing favorably with SF-36. These findings suggest its utility for measuring disease-specific HQOL changes after VS.

Pheochromocytoma of the heart.

This is a presentation of a unique case of cardiac pheochromocytoma during pregnancy. The case is significant because pheochromocytoma is a difficult diagnosis and its rarity during pregnancy may lead to this important diagnosis being overlooked, even though treatment is specific and highly successful.

Predictors of mortality for patients undergoing cardiac valve replacements in New York State.

BACKGROUND: The objective of this study was to identify the mortality rates and significant independent risk factors for mortality for each of six valve replacement groups. METHODS: A total of 14,190 patients who underwent valve replacement in New York State from 1995 to 1997 were classified into six major groups and significant independent risk factors for inpatient mortality were identified for each of the groups using stepwise logistic regression. RESULTS: Mortality rates ranged from 3.33% for isolated aortic valve surgical procedures to 18.72% for multiple valve replacements with coronary artery bypass graft operations. The number of years in excess of age 55 was a significant multivariate predictor of mortality for all six groups of patients. Shock was a significant predictor for five of the six groups, and in each of those groups it was the risk factor with the highest odds ratio. CONCLUSIONS: Significant patient risk factors are relatively consistent across different types of valve replacement procedures. The probability of survival from valve surgical procedures is highly dependent on the patient's preoperative profile and the type of valve operation.

Transmyocardial laser revascularization with excimer laser: clinical results at 1 year.

BACKGROUND: Transmyocardial laser revascularization, a new strategy for the treatment of diffuse ischemic heart disease, uses laser technology for the theoretical purpose of forming transmyocardial channels in the heart to increase perfusion to ischemic zones. This report summarizes our initial clinical experience with the procedure. METHODS: Excimer transmyocardial laser revascularization was performed in a reversibly ischemic region of the heart in 15 patients. Ischemia and myocardial viability were evaluated by assessment of symptoms and of results of radionuclide single photon emission computed tomography imaging, exercise tolerance testing, and 24-hour Holter monitoring. RESULTS: No adverse events occurred as a result of the laser revascularization, although 1 patient with preoperative ventricular arrhythmias died 48 hours postoperatively as a result of refractory ventricular tachycardia. Angina class decreased significantly from base line values in patients who had undergone the procedure (mean Canadian Cardiovascular Association angina class, 3.5+/-0.5 at base line, 1.6+/-0.6 at 1 month, 1.5+/-0.8 at 3 months, 1.9+/-0.9 at 6 months, 1.8+/-0.8 at 12 months; p<0.002), and nitroglycerin requirements were similarly decreased in patients who had undergone laser revascularization (mean g/wk of sublingual nitroglycerin, 19+/-4 at baseline, 5+/-3 at 1 month, 4+/-2 at 3 months, 4+/-2 at 6 months, 2+/-1 at 12 months; p<0.02). Exercise tolerance testing demonstrated increase in exercise duration compared with base line values (mean minutes, 7.4+/-3.1 at base line, 8.0+/-3.9 at 1 month, 8.5+/-4.4 at 3 months, and 9.0+/-3.9 at 12 months; p>0.05); those increases were not large enough to be statistically significant, however. CONCLUSIONS: Our data are consistent with the concept that excimer transmyocardial laser revascularization in individuals with significant ischemic heart disease appears to be well tolerated, can be performed safely, and may lead to a reduction in ischemic symptomatology.

Severe mitral regurgitation due to mitral valve prolapse: risk factors for development, progression, and need for mitral valve surgery.

Patients with mitral valve prolapse (MVP) may develop severe mitral regurgitation (MR) and require valve surgery. Preliminary data suggest that high body weight and blood pressure might add to the irreversible factors of older age and male gender in increasing risk of these complications. Fifty-four patients with severe MR due to MVP were compared with 117 control subjects with uncomplicated MVP to elucidate factors independently associated with severe MR: the need for valve surgery and the cumulative risk of requiring mitral valve surgery. Patients with severe MR were older (p<0.00005), more overweight (p = 0.002), had higher systolic (p = 0.0003) and diastolic (p = 0.007) blood pressures, and were more likely to have hypertension (p = 0.0001) and to be men (p<0.001). In both groups, men had higher blood pressure and relative body weight than women. In multivariate analysis, older age was most strongly associated with MR; higher body mass index, hypertension, and gender were independent predictors of severe MR in analyses that excluded age. Among the 54 patients with severe MR, the 32 (59%) who underwent mitral valve surgery during 11 years of follow-up were older, more overweight, and more likely to be hypertensive than those not requiring surgery. Among patients undergoing mitral valve surgery in 3 centers, mitral prolapse was the etiology in 25%, 67% of whom were men. Using these data and national statistics, we estimate that the gender-specific cumulative risk for requiring valvular surgery for severe MR in subjects with MVP is 0.8% in women and 2.6% in men before age 65, and 1.4% and 5.5% by age 75. Thus, subjects with MVP who are older, more overweight, and hypertensive are at greater risk for severe MR and valve surgery. Higher blood pressure and relative weight in men with MVP appear to contribute to the gender difference in risk for severe MR.

Preoperative predictors of late postoperative outcome among patients with nonischemic mitral regurgitation with 'high risk' descriptors and comparison with unoperated patients.

Among patients with chronic nonischemic mitral regurgitation (MR), high short-term mortality risk can be identified by left (LV) and/or right ventricular (RV) ejection fraction (EF) criteria (LVEF 20%, MVR significantly improved survival versus medical treatment (rest: p < 0.0001, exercise: p = 0.0003). In high risk MR patients, MVR improves survival; preoperative RV performance can define subgroups with different long-term postoperative survival.

Repair of traumatic aortic valve disruption and descending aortic transection.

Traumatic aortic transection after acute deceleration injury remains a highly lethal condition. Concomitant aortic valve disruption is exceedingly rare, and can complicate the timing of surgical management. This report describes the management and outcome of a patient with these types of injuries.

Focal angiogen therapy using intramyocardial delivery of an adenovirus vector coding for vascular endothelial growth factor 121.

BACKGROUND: Adenovirus (Ad) vector-mediated gene therapy strategies have emerged as promising modalities for the "biological revascularization" of tissues. We hypothesized that direct intramyocardial, as opposed to intracoronary, administration of an Ad vector coding for the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) would provide highly focal Ad genome levels, and increases in VEGF, ideal for inducing localized therapeutic angiogenesis. METHODS: Persistence and regional distribution of the vector were assessed by TaqMan real-time quantitative polymerase chain reaction technology and enzyme-linked immunosorbent assay, after intramyocardial Ad(GV)VEGF121.10 in the rat, and either intramyocardial or intracoronary (circumflex territory) vector in Yorkshire swine. Based on these results, we assessed the focal nature of the improved cardiac blood flow in a previously reported porcine myocardial ischemia model. RESULTS: Intramyocardial delivery of Ad(GV)VEGF121.10 in the rat resulted in local persistence of the Ad genome that decreased 1,000-fold over 3 weeks, with peak myocardial VEGF expression 24 to 72 h after vector delivery. After intramyocardial Ad(GV)VEGF121.10 in the circumflex distribution of pigs, Ad vector genome and VEGF protein levels were more than 1,000-fold and more than 90-fold higher, respectively, in this distribution than in other myocardial regions. In comparison, intracoronary injection yielded maximum myocardial Ad genome and VEGF levels 33-fold and 9-fold lower, respectively, than that after intramyocardial delivery. Angiograms obtained 28 days after intramyocardial Ad(GV)VEGF121.10 demonstrated rapid circumflex reconstitution via collaterals localized to the region of vector administration. CONCLUSIONS: These studies demonstrate that direct intramyocardial administration of Ad(GV)VEGF121.10 results in focal genome and VEGF levels, including focal angiogenesis, sufficient to normalize blood flow to the ischemic myocardium, findings that are relevant to designing human trials of gene therapy-mediated cardiac angiogenesis.

Predictors and outcomes of cardiac complications following elective coronary bypass grafting.

Our objective was to determine the predictors of cardiac complications among a cohort of elective coronary artery bypass graft (CABG) surgery patients and to determine the relationship of such complications to subsequent quality of life and symptoms. A total of 248 patients were enrolled and 237 completed 6 month follow-up. The combined rate of both major and minor cardiac complications was 9.7% (n = 24). Patients in this study were evaluated preoperatively, monitored intraoperatively, followed immediately postoperatively and at 6 months. Major cardiac complications accounted for 3.6% (n = 9) and minor complications for 6% (n = 15). Using multivariable logistic regression analysis, the predictors of major cardiac complications were receiving diuretics preoperatively (p = .01) and increased time during cross-clamping (p = .006). At 6 months after surgery, 19% of the patients with postoperative cardiac complications experienced worsening of symptoms, in contrast to only 8% of those without cardiac complications (p = .03). We concluded that patients who were on preoperative diuretics and those who had longer cross-clamp times were at higher risk of cardiac complications. The majority of patients who had acute cardiac complications had improved function and symptoms at 6 months postoperatively.

Six-month assessment of a phase I trial of angiogenic gene therapy for the treatment of coronary artery disease using direct intramyocardial administration of an adenovirus vector expressing the VEGF121 cDNA.

OBJECTIVE: To summarize the 6-month follow-up of a cohort of patients with clinically significant coronary artery disease who received direct myocardial injection of an E1-E3- adenovirus (Ad) gene transfer vector (Ad(GV)VEGF121.10) expressing the human vascular endothelial growth factor (VEGF) 121 cDNA to induce therapeutic angiogenesis. BACKGROUND: Therapeutic angiogenesis describes a novel approach to the treatment of vascular occlusive disease that uses the administration of growth factors known to induce neovascularization of ischemic tissues. METHODS: Direct myocardial injection of Ad(GV)VEGF121.10 into an area of reversible ischemia was carried out in 21 patients as an adjunct to conventional coronary artery bypass grafting (group A, n = 15) or as sole therapy using a minithoracotomy (group B, n = 6). RESULTS: No evidence of systemic or cardiac-related adverse events related to vector administration was observed up to 6 months after therapy. Trends toward improvement in angina class and exercise treadmill testing at 6-month follow-up in the sole therapy group suggest the effects of this therapy are persistent for > or =6 months. CONCLUSIONS: This study suggests that direct myocardial administration of Ad(GV)VEGF121.10 appears to be well tolerated in patients with clinically significant coronary artery disease. Initiation of phase II evaluation of this therapy appears warranted.

Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease.

BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Safety of direct myocardial administration of an adenovirus vector encoding vascular endothelial growth factor 121.

A gene therapy strategy involving direct myocardial administration of an adenovirus (Ad) vector encoding the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) has been shown to be capable of "biological revascularization" of ischemic myocardium in an established porcine model [Mack, C.A. (1998). J. Thorac. Cardiovasc. Surg. 115, 168-177]. The present study evaluates the local and systemic safety of this therapy in this porcine ischemia model and in normal mice. Myocardial ischemia was induced in Yorkshire swine with an ameroid constrictor 21 days prior to vector administration. Ad(GV)VEGF121.10 (10(9) or 10(10) PFU), Ad5 wild type (10(9) PFU), AdNull (control vector with no transgene; 10(9) PFU), saline, or no injection (naive) was administered in 10 sites in the ischemic, circumflex distribution of the myocardium. Toxicity was assessed by survival, serial echocardiography, blood analyses, and myocardial and liver histology at 3 and 28 days after vector administration. All pigs survived to sacrifice, except for one animal in the Ad(GV)VEGF121.10 (10(10) PFU) group, which died as a result of oversedation. Echocardiograms of Ad(GV)VEGF121.10-treated pigs demonstrated no differences in pericardial effusion, mitral valve regurgitation, or regional wall motion compared with control pigs. Intramyocardial administration of Ad(GV)VEGF121.10 included only minimal myocardial inflammation and necrosis, and no hepatic inflammation or necrosis. Only a mild elevation of the white blood cell count was encountered on day 3, which was transient and self-limited in the Ad(GV)VEGF121.10 group as compared with the saline-treated animals. As a measure of inadvertent intravascular administration of vector, normal C57/BL6 mice received intravenous Ad(GV)VEGF121.10 (10(4), 10(6), 5 x 10(7), or 10(9) PFU), AdNull (5 x 10(7) or 10(9) PFU), or saline. Toxicity was assessed by survival, blood analyses, and organ histology at 3 and 7 days after vector administration. A separate group of C57/BL6 mice received intravenous AdmVEGF164 (Ad vector encoding the murine VEGF164 cDNA), Ad(GV)VEGF121.10, AdNull (10(8) PFU each group), or saline to assess duration of expression and safety of a homologous transgene. All mice survived to sacrifice except for 40% of the mice in the highest (10(9) PFU; a dose more than 10(3)-fold higher by body weight than the efficacious dose in pigs) Ad(GV)VEGF121.10 dose group, which died on days 5-6 after vector administration. The only differences seen in the blood analyses between treated and control mice were in the very high Ad(GV)VEGF121.10 dose group (10(9) PFU), which demonstrated an anemia as well as an increase in alkaline phosphatase when compared with all other treatment groups. Hepatic VEGF levels by ELISA in AdmVEGF164-treated mice did not persist beyond 14 days after vector administration, suggesting that persistent expression of a homologous VEGF gene transferred with an Ad vector is not a significant safety risk. Although this is not a chronic toxicity study, these data demonstrate the safety of direct myocardial administration of Ad(GV)VEGF121.10, and support the potential use of this strategy to treat human myocardial ischemia.

A comparison of three-year survival after coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty.

OBJECTIVES: The purpose of this study was to compare 3-year risk-adjusted survival in patients undergoing coronary artery bypass graft (CABG) surgery and percutaneous transluminal coronary angioplasty. BACKGROUND: Coronary artery bypass graft surgery and angioplasty are two common treatments for coronary artery disease. For referral purposes, it is important to know the relative pattern of survival after hospital discharge for these procedures and to identify patient characteristics that are related to survival. METHODS: New York's CABG surgery and angioplasty registries were used to identify New York patients undergoing CABG surgery and angioplasty from January 1, 1993 to December 31, 1995. Mortality within 3 years of undergoing the procedure (adjusted for patient severity of illness) and subsequent revascularization within 3 years were captured. Three-year mortality rates were adjusted using proportional hazards methods to account for baseline differences in patients' severity of illness. RESULTS: Patients with one-vessel disease with the one vessel not involving the left anterior descending artery (LAD) or with less than 70% LAD stenosis had a statistically significantly longer adjusted 3-year survival with angioplasty (95.3%) than with CABG surgery (92.4%). Patients with proximal LAD stenosis of at least 70% had a statistically significantly longer adjusted 3-year survival with CABG surgery than with angioplasty regardless of the number of coronary vessels diseased. Also, patients with three-vessel disease had a statistically significantly longer adjusted 3-year survival with CABG surgery regardless of proximal LAD disease. Patients with other one-vessel or two-vessel disease had no treatment-related differences in survival. CONCLUSIONS: Treatment-related survival benefit at 3-years in patients with ischemic heart disease is predicted by the anatomic extent and specific site of the disease, as well as by the treatment chosen.

Posterior distribution of infarcts in strokes related to cardiac operations.

BACKGROUND: Stroke complicates cardiac surgical procedures in a substantial number of patients. The mechanism of stroke is predominantly embolic, although hypoperfusion may play a role. The aim of this study was to determine whether radiologic appearances in this population were consistent with an embolic cause. METHODS: We reviewed computed tomographic scans and medical records in 24 patients who suffered stroke after cardiac operation. Stroke was evident at 24 hours in 19 patients (79%). Infarcts were multiple in 16 and single in 3 patients (group 1). The remaining 5 patients suffered stroke beyond 24 hours and had single infarcts on computed tomographic scan (group 2). RESULTS: In group 1, 15 patients (79%) had bilateral cerebellar infarcts, 4 (74%) had posterior cerebral artery infarcts, 10 (53%) had posterior watershed infarcts, and 11 patients (58%) had middle cerebral artery branch infarcts. The mean number of vascular territories involved was 5.1 (range, 1 to 10). Mobile atheromatous plaque was present in the ascending aorta or arch in 5 of 9 patients (56%) in group 1. In group 2, stroke occurred in close association with atrial or ventricular fibrillation in 3 of 5 patients (60%). CONCLUSIONS: In patients with radiologic evidence of infarction, perioperative strokes after cardiac operation are typically multiple, and involve the posterior parts of the brain, consistent with atheroembolization. Delayed strokes may be attributable to cardiogenic embolism.

Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion.

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, and transgene expression from adenovirus vectors can provide in vivo delivery of proteins. On the basis of this knowledge, we hypothesized that local administration of a replication-deficient adenovirus vector expressing complementary DNA for VEGF (AdVEGF) would induce collateral vessel formation in the setting of ischemia that could protect against subsequent acute vascular occlusion. METHODS: Hindlimb ischemia was induced in Sprague-Dawley rats by means of unilateral ligation of the common iliac artery immediately followed by administration of 4 x 10(9)-plaque-forming units VEGF, the control vector AdNull, or phosphate-buffered saline solution into the iliofemoral adipose tissue and thigh muscles. Untreated rats with common iliac ligation were used as an additional control group. RESULTS: Local VEGF expression was observed for 5 days in AdVEGF-treated rats but not in controls. Three weeks after ligation and vector administration, the ipsilateral femoral artery was ligated for a model of an acute vascular occlusion in the setting of preexisting ischemia. Blood flow to the ischemic hindlimb relative to the contralateral hindlimb evaluated with color microspheres demonstrated significantly increased blood flow in the AdVEGF-treated rats compared with each control group (p < 0.0001). Relative blood flow assessed by means of 99mTc-sestamibi radionuclide scans also demonstrated increased blood flow to the ligated hindlimb of AdVEGF-treated rats compared with each control group (p < 0.002). AdVEGF-treated rats also demonstrated increased vascularity in the ligated limb compared with each control group as assessed by means of angiography (p < 0.0001) and histologic quantification of blood vessels less than 80 microm diameter in local adipose tissue and capillaries per muscle fiber (p < 0.0002). AdVEGF treatment prevented a rise in femoral venous lactate femoral venous concentrations 1 hour after femoral artery ligation in control rats (p < 0.04). CONCLUSIONS: An adenovirus vector expressing VEGF complementary DNA is capable of stimulating an angiogenic response that protects against acute vascular occlusion in the setting of preexisting ischemia, suggesting that in vivo gene transfer of VEGF complementary DNA might be useful in prophylaxis of advancing arterial occlusive disease.

Prediction of indications for valve replacement among asymptomatic or minimally symptomatic patients with chronic aortic regurgitation and normal left ventricular performance.

BACKGROUND: Optimal criteria for valve replacement are unclear in asymptomatic/minimally symptomatic patients with aortic regurgitation (AR) and normal left ventricular (LV) performance at rest. Moreover, previous studies have not assessed the prognostic capacity of load-adjusted LV performance ("contractility") variables, which may be fundamentally related to clinical state. Therefore, 18 years ago, we set out to test prospectively the hypothesis that objective noninvasive measures of LV size and performance and, specifically, of load-adjusted variables, assessed at rest and during exercise (ex), could predict the development of currently accepted indications for operation for AR. METHODS AND RESULTS: Clinical variables and measures of LV size, performance, and end-systolic wall stress (ESS) were assessed annually in 104 patients by radionuclide cineangiography at rest and maximal ex and by echocardiography at rest; ESS was derived during ex. During an average 7.3-year follow-up among patients who had not been operated on, 39 of 104 patients either died suddenly (n = 4) or developed operable symptoms only (n = 22) or subnormal LV performance with or without symptoms (n = 13) (progression rate=6.2%/y). By multivariate Cox model analysis, change (delta) in LV ejection fraction (EF) from rest to ex, normalized for deltaESS from rest to ex (deltaLVEF-deltaESS index), was the strongest predictor of progression to any end point or to sudden cardiac death alone. Unadjusted deltaLVEF was almost as efficient. Symptom status modified prediction on the basis of the deltaLVEF-deltaESS index. The population tercile at highest risk by deltaLVEF-deltaESS progressed to end points at a rate of 13.3%/y, and the lowest-risk tercile progressed at 1.8%/y. CONCLUSIONS: Currently accepted symptom and LV performance indications for valve replacement, as well as sudden cardiac death, can be predicted in asymptomatic/minimally symptomatic patients with AR by load-adjusted deltaLVEF-deltaESS index, which includes data obtained during exercise.

Retrograde autologous priming for cardiopulmonary bypass: a safe and effective means of decreasing hemodilution and transfusion requirements.

OBJECTIVES: The obligatory hemodilution resulting from crystalloid priming of the cardiopulmonary bypass circuit represents a major risk factor for blood transfusion in cardiac operations. We therefore examined whether retrograde autologous priming of the bypass circuit would result in decreased hemodilution and red cell transfusion. METHODS: Sixty patients having first-time coronary bypass were prospectively randomized to cardiopulmonary bypass with or without retrograde autologous priming. Retrograde autologous priming was performed at the start of bypass by draining crystalloid prime from the arterial and venous lines into a recirculation bag (mean volume withdrawal: 880 +/- 150 ml). Perfusion and anesthetic techniques were otherwise identical for the two groups. The hematocrit value was maintained at a minimum of 16% and 23% during and after cardiopulmonary bypass, respectively, in all patients. Patients were well matched for all preoperative variables, including established transfusion risk factors. Subsequent hemodynamic parameters, pressor requirements, and fluid requirements were equivalent in the two groups. RESULTS: The lowest hematocrit value during cardiopulmonary bypass was 22% +/- 3% versus 20% +/- 3% in patients subjected to retrograde autologous priming and in control patients, respectively (p = 0.002). One (3%) of 30 patients subjected to retrograde autologous priming had intraoperative transfusion, and seven (23%) of 30 control patients required transfusion during the operation (p = 0.03). The number of patients receiving any homologous red cell transfusions in the two groups during the entire hospitalization was eight of 30 (27%; retrograde autologous priming) versus 16 of 30 (53%; control) (p = 0.03). CONCLUSIONS: These data suggest that retrograde autologous priming is a safe and effective means of significantly decreasing hemodilution and the number of patients requiring red cell transfusion during cardiac operations.

Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart.

OBJECTIVES: Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, can be delivered to targeted tissues by means of a replication-deficient adenovirus (Ad) vector. We hypothesized that direct administration of Ad vector expressing the VEGF121 complementary deoxyribonucleic acid (AdGVVEGF121.10) into regions of ischemic myocardium would enhance collateral vessel formation and improve regional perfusion and function. METHODS: Yorkshire swine underwent thoracotomy and placement of an Ameroid constrictor (Research Instruments & MFG, Corvallis, Ore.) on the circumflex coronary artery. Three weeks later, myocardial perfusion and function were assessed by single photon emission computed tomography imaging (SPECT) with 99mTc-labeled sestamibi and by echocardiography during rest and stress. AdGVVEGF121.10 (n = 7) or the control vector, AdNull (n = 8), was administered directly into the myocardium at 10 sites in the circumflex distribution (10(8) pfu/site). Four weeks later, these studies were repeated and ex vivo angiography was performed. RESULTS: SPECT imaging 4 weeks after vector administration demonstrated significant reduction in the ischemic area at stress in AdGVVEFG121.10-treated animals compared with AdNull control animals (p = 0.005). Stress echocardiography at the same time demonstrated improved segmental wall thickening in AdGVVEGF121.10 animals compared with AdNull control animals (p = 0.03), with AdGVVEGF121.10 animals showing nearly normalized function in the circumflex distribution. Collateral vessel development assessed by angiography was also significantly greater in AdGVVEGF121.10 animals than in AdNull control animals (p = 0.04), with almost complete reconstitution of circumflex filling in AdGVVEGF121.10 animals. CONCLUSIONS: An Ad vector expressing the VEGF121 cDNA induces collateral vessel development in ischemic myocardium and results in significant improvement in both myocardial perfusion and function. Such a strategy may be useful in patients with ischemic heart disease in whom complete revascularization is not possible.

Cardiac operations in patients with cirrhosis.

BACKGROUND: A retrospective review was performed to determine the outcome after cardiac operations in patients with a documented history of noncardiac cirrhosis. METHODS: The charts of patients admitted to the cardiothoracic surgical service between 1990 and 1996 were reviewed, and 13 patients with a preoperative history of cirrhosis were identified. The severity of preoperative liver disease was graded according to the criteria of Child. RESULTS: Most of the cases of cirrhosis were alcohol-related. Eight patients were classified as having Child class A and 5 as having Child class B cirrhosis. One hundred percent of patients with Child class B and 25% of those with Child class A cirrhosis had major complications. The postoperative chest tube output and transfusion requirements of these patients were approximately three times higher than average. The overall perioperative mortality rate was 31%. In patients with Child class B cirrhosis, the mortality rate was 80%. No patient with Child class A cirrhosis died. Deaths were related to gastrointestinal and septic complications, and not to cardiovascular failure. CONCLUSIONS: These findings suggest that patients with minimal clinical evidence of cirrhosis can tolerate cardiopulmonary bypass and cardiac surgical procedures, whereas those with more advanced liver disease should not be offered operation.

Comprehensive multimodality blood conservation: 100 consecutive CABG operations without transfusion.

BACKGROUND: Despite the recent introduction of a number of technical and pharmacologic blood conservation measures, bleeding and allogeneic transfusion remain persistent problems in open heart surgical procedures. We hypothesized that a comprehensive multimodality blood conservation program applied algorithmically on the basis of bleeding and transfusion risk would provide a maximum, cost-effective, and safe reduction in postoperative bleeding and allogeneic blood transfusion. METHODS: One hundred consecutive patients undergoing coronary artery bypass grafting were prospectively enrolled in a risk factor-based multimodality blood conservation program (MMD group). To evaluate the relative efficacy and safety of this comprehensive approach, comparison was made with a similar group of 90 patients undergoing coronary artery bypass grafting to whom the multimodality blood conservation program was not applied but in whom an identical set of transfusion guidelines was enforced (control group). To evaluate the cost effectiveness of the multimodality program, comparison was also made between patients in the MMD group and a consecutive series of contemporaneous, diagnostic-related group-matched patients. RESULTS: One hundred consecutive patients in the MMD group underwent coronary artery bypass grafting without allogeneic transfusion. This compared favorably with the control population in whom a mean of 2.2 +/- 6.7 units of allogeneic blood was transfused per patient (34 patients [38%] received transfusion). In addition, the volume of postoperative blood loss at 12 hours in the control group was almost double that of the MMD group (660 +/- 270 mL versus 370 +/- 180 mL [p < 0.001]). Total costs for the MMD group in each of the three major diagnostic-related groups were equivalent to or significantly less than those in the consecutive series of diagnostic-related group-matched patients. CONCLUSIONS: Comprehensive risk factor-based application of multiple blood conservation measures in an optimized, integrated, and algorithmic manner can significantly decrease bleeding and need of allogeneic transfusion in coronary artery bypass grafting in a safe and cost-effective manner.