Risk factors for ischemic optic neuropathy after cardiopulmonary bypass: a matched case/control study.

UNLABELLED: Visual loss (acuity or field) secondary to ischemic optic neuropathy (ION) is a rare but devastating complication of cardiac surgery involving cardiopulmonary bypass (CPB). We determined clinical features and risk factors for ION by a retrospective time-matched, case-control study. ION was identified in 17 (0.06%) patients out of 27,915 patients who underwent CPB between January 1, 1976, and December 31, 1994. For each ION patient, two patients who underwent CPB exactly 2 wk before the ION patient were selected as controls. Data were analyzed by using conditional logistic regression with the 1:2 matched-set feature of 17 cases and 34 controls. Two-tailed P values < or =0.05 were considered significant. From bivariate analysis, smaller minimum postoperative hemoglobin concentration (odds ratio [OR] = 1.9, P = 0.047) and the presence of atherosclerotic vascular disease (OR = 7.0, P = 0.026) were found to be independently associated with ION after CPB, as were smaller minimum postoperative hemoglobin concentration (OR = 2.2, P = 0.027) and preoperative angiogram within 48 h of surgery (OR = 7.2, P = 0.042). In ION patients, 13 (76.5%) of 17 experienced a minimum postoperative hemoglobin value of < 8.5 g/dL, whereas only 14 (41.2%) of 34 control patients experienced values < 8.5 g/dL. IMPLICATIONS: Patients with clinically significant vascular disease history or preoperative angiogram may be at increased risk for ischemic optic neuropathy after cardiac surgery, especially if the hemoglobin remains low in the postoperative period.

Surgical management of left-sided carcinoid heart disease.

BACKGROUND: Carcinoid involvement of left-sided heart valves has been reported in patients with a patent foramen ovale, carcinoid tumor of the lung, and active carcinoid syndrome with high levels of serotonin. The present study details the clinical features and surgical management of patients with carcinoid heart disease affecting both left- and right-sided valves. METHODS AND RESULTS: Eleven patients (7 men, 4 women) with symptomatic carcinoid heart disease underwent surgery for left- and right-sided valve disease between 1989 and 1999. Mean age was 57+/-9 years, and median preoperative NYHA class was 3. All patients had metastatic carcinoid tumors and were on somatostatin analog. Of 11 patients, 5 (45%) had a patent foramen ovale; 1 of these also had a primary lung carcinoid tumor. Surgery included tricuspid valve replacement in all patients, pulmonary valve replacement in 3 and valvectomy in 7, mitral valve replacement in 6 and repair in 1, aortic valve replacement in 4 and repair in 2, CABG in 2, and patent foramen ovale closure in 5. One myocardial metastatic carcinoid tumor was removed. There were 2 perioperative deaths. At a mean follow-up of 41 months, 4 additional patients were dead. All but 1 surgical survivor initially improved >/=1 functional class. No patient required reoperation. CONCLUSIONS: Carcinoid heart disease may affect left- and right-sided valves and occurred without intracardiac shunting in 55% of this surgical series. Despite metastatic disease that limits longevity, operative survivors had improvement in functional capacity. Cardiac surgery should be considered for select patients with carcinoid heart disease affecting left- and right-sided valves.

Entrapment of subvalvular mitral tissue causing intermittent failure of a St Jude mitral prosthesis.

Frequently portions of the mitral valve and sub-valvular apparatus are left intact during mitral valve replacement to help preserve left ventricular function. We describe a patient with paroxysmal congestive heart failure caused by intermittent entrapment of the subvalvular apparatus in the prosthesis, preventing complete valve closure.

Natriuretic peptide levels in atrial fibrillation: a prospective hormonal and Doppler-echocardiographic study.

OBJECTIVES: The objective was to determine the independent association between atrial fibrillation (A-Fib) and activation of natriuretic peptides. BACKGROUND: The association of A-Fib with activation of N-terminal atrial and brain natriuretic peptides (N-ANPs and BNPs, respectively) is uncertain but of great importance for the diagnostic utilization of natriuretic peptides. This uncertainty is related to the lack of appropriate controls, with left ventricular (LV) and atrial overload similar to A-Fib. METHODS: We prospectively measured N-terminal atrial and BNPs and endothelin-1 levels in 100 patients and 14 age- and gender-matched control subjects. The 32 patients with A-Fib were compared with 68 patients in sinus rhythm and similar LV and atrial overload (due to mitral regurgitation or LV dysfunction) measured simultaneously with hormonal levels with comprehensive Doppler echocardiography. RESULTS: Patients with A-Fib compared with those in sinus rhythm had similar symptoms, comorbid conditions, cardioactive medications, pulmonary pressure, left atrial volume, and LV ejection fraction and filling characteristics but demonstrated higher N-ANP levels (2,613 +/- 1,681 vs. 1,654 +/- 1,323 pg/ml, p = 0.007) even after adjustment for the underlying cardiac disease (p < 0.0001). Conversely, BNP levels were similar in both groups (165 +/- 163 vs. 160 +/- 269 pg/ml, p = 0.9). In multivariate analysis, a higher N-ANP level was associated with A-Fib (p = 0.0003), symptom class (p < 0.0001) and endothelin-1 level (p = 0.032) independently of left atrial volume and LV ejection fraction. Conversely, BNP showed no independent association with and was most strongly associated with LV ejection fraction (p < 0.0001). CONCLUSIONS: Atrial fibrillation is an independent determinant of higher N-ANP levels and blurs its association with LV dysfunction. Conversely, the BNP is not independently associated with A-Fib and is strongly determined by LV dysfunction, for which it is an independent marker.

Intraoperative transesophageal echocardiography: 5-year prospective review of impact on surgical management.

OBJECTIVE: To determine the impact of intraoperative transesophageal echocardiography (IOTEE), an important adjunct in many types of cardiac surgical cases, on the surgical decisions made perioperatively in adult patients undergoing cardiac surgery. PATIENTS AND METHODS: All adult patients who had cardiac surgery between 1993 and 1997 and who also had IOTEE were studied. New findings before and after cardiopulmonary bypass and alterations in the planned surgical procedure or management were documented prospectively. RESULTS: A total of 3245 patients (60% men, 40% women; aged 18-93 years with a mean +/- SD age of 62 +/- 15 years) were included in the study. The most common operations performed were mitral valve repair (26%) and aortic valve replacement (22%). Over the 5-year period, 41% of patients had IOTEE. New information was found before bypass in 15% of patients, directly affecting surgery in 14% of the patients. The most common new prebypass information found was patent foramen ovale resulting in closure in the majority of patients. New information was found after bypass in 6% of the patients, resulting in a change in surgery or hemodynamic management in 4% of the total. The most common postbypass finding was valvular dysfunction with repeat bypass in most patients for re-repair or replacement. No major complications occurred. CONCLUSION: In adult patients undergoing cardiac surgery, IOTEE provides important important information both before and after bypass that affects surgical and hemodynamic management.

Pitfalls and results of immediate angiography after off-pump coronary artery bypass grafting.

BACKGROUND: We sought to determine the feasibility of off-pump coronary artery bypass grafting (OPCAB) in a consecutive series and prospectively assess the value of immediate post-operative coronary angiography. METHODS: All patients referred for coronary artery bypass grafting, within a four-month period, were approached as candidates for OPCAB. All 50 OPCAB patients were studied by immediate post-operative coronary angiography. RESULTS: The OPCAB procedure was feasible in 67% of patients (50/75). Five of 55 patients (9.1%) were converted to on-pump procedures, three for hemodynamic instability, and two because of deeply intramyocardial vessels. The other 20 underwent on-pump revascularization for anatomical and physiological reasons. The average age of OPCAB patients was 68.1 +/- 9.6 years; 26% were female, 74% male. Two (4%) were redo operations. Mean number of grafts was 2.9 +/- 0.8, 51 internal thoracic artery grafts (ITA), 17 radial artery grafts (RA), and 76 saphenous vein grafts (SVG). Angiographic graft patency was 90.2% for ITA, 88.2% for RA, and 96.1% for SVG. Interpretation of catheterization results was confounded by significant native and arterial graft spasm. Six of seven occluded arterial grafts and one of three SVG were probe patent at immediate reoperation (all had adequate flow by intra-operative doppler at the initial operation). Only two graft occlusions were noted in the 18 patients who did not receive protamine. The patency rate was 95.6% (131/137) when the probe patent anastomoses were excluded. Seven patients (14%) returned to the OR as a result of the catheterization findings; five to revise occluded grafts, one to improve the lie of a kinked SVG, and one to graft an intramyocardial intermediate ramus when an adjacent high diagonal was grafted instead (two of seven on-pump). All graft problems were found in the absence of hemodynamic instability or electrocardiogram changes. In-hospital mortality was 2% (1). Complications in survivors were atrial fibrillation in 12 patients (24.5%), permanent pacemaker in one (2%), endotracheal bleeding in one (2%), and take-back for bleeding in one (2%). CONCLUSIONS: There were a significant number of unexpected arterial graft occlusions. The reversal of heparin and ITA spasm appeared to be contributory. All patients with occluded grafts had no signs of trouble. Interpretation of immediate post-operative catherization is difficult because of significant native vessel and graft spasm. It reliably determines patency but it's value is suspect for determination of long-term graft adequacy.

Study of FK-binding protein: FK506-metabolite complexes by electrospray mass spectrometry: correlation to immunosuppressive activity.

Electrospray ionization mass spectrometry was used to study several non-covalent FK-binding protein (FKBP) immunosuppressant complexes in the gas phase. Relative FKBP binding affinities were determined from the signal ratio for the 7+ charge states of bound and unbound complexes as a function of capillary exit voltage. All complexes displayed a 1:1 binding stoichiometry. The relative gas-phase binding affinities were found to be well correlated with in vitro FKBP binding and in vitro immunosuppression (rapamycin > FK506 > or = 31-demethyl FK506 > 13-demethyl FK506 >> Cyclosporin A; CsA). The method demonstrates potential as a simple, rapid, and automatable technique for prediction of the immunosuppressive activity of FKBP:drug complexes.

Comparison of intraoperative transesophageal echocardiographic examinations with the operative findings: prospective review of 1918 cases.

The purpose of this study was to prospectively compare the intraoperative transesophageal echocardiographic (IOTEE) findings with the operative findings in 1918 consecutive cardiac cases. Forty-eight discordant findings were found between the IOTEE and operative findings. Of the 48 discordant findings, most were related to valve pathology. Structural abnormalities that were missed by IOTEE included those of the aortic valve, 12 cases (25%), mitral valve, 13 cases (27%), and pulmonic and tricuspid valves, 5 cases (10%). Functional discrepancies occurred in 8% of cases. Overall, incidence of discrepant findings between IOTEE and operative findings was low (2.5%). This resulted in an alteration of the planned surgical procedure in a small number of cases (0.3%).

A prospective, randomized study of cardiopulmonary bypass temperature and blood transfusion.

BACKGROUND: We hypothesized that normothermic cardiopulmonary bypass (CPB) would be associated with decreased blood loss and allogeneic transfusion requirements relative to hypothermic CPB. METHODS: After obtaining institutional review board approval and informed patient consent, we conducted a prospective, randomized study of 79 patients undergoing CPB for a primary cardiac operation at normothermic (37 degrees C) (n = 44) or hypothermic temperature (25 degrees C) (n = 35). Blood loss and transfusion requirements in the operating room and for the first 24 hours in the intensive care unit were determined. A paired t test and rank sum tests were used. A p value of less than 0.05 was considered significant. RESULTS: The normothermic and hypothermic CPB groups did not differ in demographic variables, CPB or cross-clamp duration, heparin sodium or protamine sulfate dose, prothrombin time, or thromboelastogram results. There were no differences between the two CPB groups in blood loss or transfusion requirements. CONCLUSIONS: We found that when there was no difference in duration of CPB, normothermic and hypothermic CPB groups demonstrated similar blood loss and transfusion requirements even though other studies have shown hypothermia induces platelet dysfunction and alters the activity of the coagulation cascade.

Noncardiac surgery in Eisenmenger syndrome.

OBJECTIVES: The purpose of this study was to evaluate the morbidity and mortality associated with noncardiac surgery (NCS) in patients (pts) with Eisenmenger syndrome. BACKGROUND: Noncardiac surgery in pts with Eisenmenger syndrome is associated with increased cardiovascular complications. METHODS: Fifty-eight pts with Eisenmenger syndrome (17M, 41F aged 18 to 69 years (mean 41 years) who had been followed for up to 41.5 years (mean 9.3 years) were retrospectively evaluated for any NCS done at > or = 17 years of age. RESULTS: Twenty-four pts had a total of 28 NCSs at an age of 17 to 55 years (mean 29 years) including 9 tubal ligations, 3 neurosurgeries, 3 cholecystectomies, 3 hysterectomies, 3 vasectomies, and 1 each spinal fusion, appendectomy, eye enucleation, hernia repair, hand surgery, tonsillectomy and therapeutic abortion. There were two deaths (7%), one following spinal fusion and the other following appendectomy at another institution. Fourteen of these NCSs were performed at our institution, including 11 under general anesthesia. The duration of anesthesia varied from 75 to 525 min (mean 165 min). All pts remained in sinus rhythm. The lowest systolic blood pressure (BP) ranged from 78 to 125 mm Hg. Of those 11 pts, 9 were extubated immediately after surgery and 2 needed dopamine. Ten patients were discharged without any complications, including 3 within 1 day of surgery. One death occurred 10 days following spinal fusion. This pt had the longest anesthesia (525 min) and an intraoperative systolic BP as low as 78 mm Hg. She also needed the largest fluid administration (6,475 cc) in addition to postoperative mechanical ventilation and dopamine. CONCLUSIONS: Adult pts with Eisenmenger syndrome are at increased risk with NCS, but with current/modern techniques, the risk of death is less than previously thought. In the vast majority of cases, NCS can be undertaken without substantial morbidity, and early extubation is achievable. However, even with relatively minor surgery, significant complications, including death, can occur. Referral to major centers with expertise in the care of pts with Eisenmenger syndrome is advisable.

Role of emergency intraoperative transesophageal echocardiography.

Transesophageal echocardiography (TEE) has a definitive role in the diagnosis and management of critically ill patients with cardiovascular disease and patients undergoing cardiac operations. The diagnostic role of emergency intraoperative TEE and the impact on clinical outcome have not been evaluated. We reviewed the indications, findings, and impact of emergency intraoperative TEE in 66 patients over a 4-year period. The indications for emergency TEE were unexplained hemodynamic instability (36 patients), preoperative evaluation of patients having emergency surgery (19 patients), cardiac evaluation of trauma cases (6 patients), and unexplained intraoperative hypoxemia (5 patients). New findings were disclosed in 53 (80%) patients, with an alteration of the planned surgical procedure in 15 (23%). Despite the therapeutic impact, 24 patients (36%) did not survive to hospital dismissal. We recommend that TEE be considered as the diagnostic tool of choice when surgical patients have unexplained hemodynamic instability, when time does not permit complete preoperative evaluation, when cardiovascular injury is suspected in a trauma patient, and to evaluate unexplained hypoxemia.

Mitral regurgitation: a new clinical perspective.

Mitral regurgitation is a common valvular heart disease, particularly in the elderly population. The timing of surgical repair is controversial, but recent literature suggests a new clinical perspective on the management of this disease. Despite receiving medical treatment and having few initial symptoms, patients with mitral regurgitation due to flail leaflets have an excess mortality rate (6.3% per year) and high morbidity. Ten years after mitral regurgitation has been diagnosed, 90% of the patients have either died or undergone an operation. After surgical correction of mitral regurgitation, left ventricular dysfunction is a frequent complication and is the cause of excess heart failure and mortality. This complication is due to preoperative left ventricular dysfunction but is incompletely predictable with use of current methods. Conversely, considerable progress in surgery has resulted in an extremely low operative mortality rate (about 1% in patients younger than 75 years of age) and high feasibility of valve repair, even in patients with anterior leaflet prolapse. These facts have led to the new perspective that early surgical correction (before occurrence of overt symptoms or left ventricular dysfunction) should be considered when patients are diagnosed with severe mitral regurgitation.

Resection of a large temporooccipital parenchymal arteriovenous fistula by using deep hypothermic circulatory bypass. Case report.

The authors believe this to be the first published case in which a deep hypothermic cardiopulmonary bypass was used to facilitate resection of a large parenchymal arteriovenous fistula. The use of this procedure facilitated resection of the lesion by allowing compression and manipulation of large venous varices that were overlying the deeper arterial feeding vessels. The surgical rationale, technique, and intra- and postoperative management are discussed.

Cytotoxic quinolines (Part 3). Synthesis of 1-azolylalkyl-4(1H)-quinolones as cytotoxic agents.

A series of 1-azolylalkyl-4(1H)-quinolones has been synthesized and evaluated for cytotoxic activity both in vitro and in vivo. The effects on cytotoxicity of varying substitution on the quinoline moiety was investigated. The insertion of a 5-amino group proved to be the most effective modification, resulting in a several-fold increase in cytotoxicity in vitro. Previously reported results indicated that the activity of this class of compounds may involve topoisomerase inhibition, but investigation of the current compounds has ruled out this possibility. One compound, 13, showed in vitro cytotoxicity notably superior to Adriamycin, however it demonstrated only slight or no in vivo efficacy depending on the model used.

Cytotoxic quinolines (part 1). Azolylalkyloxy quinolines and 1-azolylalkyl-4(1H)-quinolones.

A series of 4-azolylalkyloxyquinolines and 1-azolylalkyl-4(1H)-quinolones has been synthesized and evaluated for cytotoxicity against various cancer cell lines. 1-Phenyl-1,2,3-triazole and 1-methylpyrazole were found to be the most effective azoles. The length of the alkyl chain was critical, with 8 to 10 carbon atoms being optimal. Several of the compounds were found to be very cytotoxic in vitro towards various cancer cells. Compounds 9o, 10k, and 10r were evaluated in vivo, but were ineffective and exhibited acute general toxicity at higher dosages.

Cytotoxic quinolines (part 2). Azolylalkylamino and-thio quinolines.

A series of azolylalkylaminoquinolines and azolylalkylthioquinolines was synthesized and evaluated for cytotoxicity against various cancer cell lines. Structure-activity relationships previously established for azolylalkyloxyquinolines were generally found to apply for the present compounds. The azolylalkylaminoquinolines were found to be more cytotoxic than the corresponding thio compounds. Oxidation of 11a to sulfones 12 and 13 resulted in a reduction of cytotoxicity. Several of the compounds were found to be very cytotoxic in vitro towards different cancer cell lines. Compound 7d, the most cytotoxic in vitro against the P388 cell line in this series, was ineffective in vivo and exhibited significant general toxicity at higher dosages.

Cemented versus noncemented total hip arthroplasty--embolism, hemodynamics, and intrapulmonary shunting.

Bone cement implantation syndrome is characterized by hypotension, hypoxemia, cardiac arrhythmias, cardiac arrest, or any combination of these complications. It may result from venous embolization that occurs in conjunction with intramedullary hypertension in the femur during insertion of the prosthesis in patients undergoing cemented total hip arthroplasty (THA). Intramedullary hypertension does not occur in patients undergoing noncemented THA. In this study, we sought to compare embolization between patients undergoing cemented and noncemented THA and to determine whether this state resulted in cardiorespiratory deterioration. In this prospective investigation of 35 patients undergoing elective THA, we used transesophageal echocardiography and invasive hemodynamic monitoring, and in 12 of them, we monitored distribution of pulmonary ventilation and perfusion intraoperatively. Embolization was significantly greater after insertion of the prosthesis in patients undergoing cemented than in those undergoing noncemented THA. Cemented THA was also associated with decreased cardiac output and increased pulmonary artery pressure and pulmonary vascular resistance. Increases in ventilation-perfusion mismatching, however, could not be demonstrated 30 minutes after insertion of the femoral prosthesis. Intraoperative monitoring for embolism may help physicians assess patients in whom cardiorespiratory function deteriorates during THA.

Intraoperative evaluation of mitral valve regurgitation and repair by transesophageal echocardiography: incidence and significance of systolic anterior motion.

OBJECTIVE: This study was designed to delineate the utility and results of intraoperative transesophageal echocardiography in the evaluation of patients undergoing mitral valve repair for mitral regurgitation. BACKGROUND: Mitral valve reconstruction offers many advantages over prosthetic valve replacement. Intraoperative assessment of valve competence after repair is vital to the effectiveness of this procedure. METHODS: Intraoperative transesophageal echocardiography was performed in 143 patients undergoing mitral valve repair over a period of 23 months. Before and after repair, the functional morphology of the mitral apparatus was defined by two-dimensional echocardiography; Doppler color flow imaging was used to clarify the mechanism of mitral regurgitation and to semiquantitate its severity. RESULTS: There was significant improvement in the mean mitral regurgitation grade by composite intraoperative transesophageal echocardiography after valve repair (3.6 +/- 0.8 to 0.7 +/- 0.7; p less than 0.00001). Excellent results from initial repair with grade less than or equal to 1 residual mitral regurgitation were observed in 88.1% of patients. Significant residual mitral regurgitation (grade greater than or equal to 3) was identified in 11 patients (7.7%); 5 underwent prosthetic valve replacement, 5 had revision of the initial repair and 1 patient had observation only. Of the 100 patients with a myxomatous mitral valve, the risk of grade greater than or equal to 3 mitral regurgitation after initial repair was 1.7% in patients with isolated posterior leaflet disease compared with 22.5% in patients with anterior or bileaflet disease. Severe systolic anterior motion of the mitral apparatus causing grade 2 to 4 mitral regurgitation was present in 13 patients (9.1%) after cardiopulmonary bypass. In 8 patients (5.6%), systolic anterior motion resolved immediately with correction of hyperdynamic hemodynamic status, resulting in grade less than or equal to 1 residual mitral regurgitation without further operative intervention. Transthoracic echocardiography before hospital discharge demonstrated grade less than or equal to 1 residual mitral regurgitation in 86.4% of 132 patients studied. A significant discrepancy (greater than 1 grade) in residual mitral regurgitation by predischarge transthoracic versus intraoperative transesophageal echocardiography was noted in 17 patients (12.9%). CONCLUSIONS: Transesophageal echocardiography is a valuable adjunct in the intraoperative assessment of mitral valve repair.