Optimal timing of aortic valve replacement for aortic stenosis--are we operating late?

OBJECTIVE: To evaluate the adherence to current guidelines for surgery in patients with aortic valve stenosis. DESIGN: From 1 January 1997 to 31 May 1999, 99 patients were accepted for aortic valve surgery with preserved left ventricular function and normal coronary angiogram. On admission for operation, 20 patients were evaluated regarding symptoms, exercise capacity, and left ventricular morphology and function. RESULTS: There were 14 men and 6 women, mean age 64.3 years. Years from symptom onset varied from 2.1 to 3.2. Dyspnoea was the most common limiting symptom. Thirty per cent of the patients were classified as NYHA IIIB. Physical capacity was reduced to 79% of the expected. Left ventricular hypertrophy was present in 14/20 patients. Left ventricular systolic function was reduced with mean ejection fraction of 0.46. Diastolic dysfunction (E/A ratio <1) was present in 12 patients. CONCLUSION: Many patients accepted for aortic valve replacement due to aortic stenosis show advanced disease and are referred for surgery later in the disease process than is recommended in the current guidelines.

Pericarbon pericardial valve prosthesis: midterm results of the aortic valve replacement.

This clinical study was undertaken to verify the encouraging results of experimental studies regarding a new pericardial bioprosthesis. From May 1989 to November 1993, 204 patients underwent an aortic valve replacement with the Pericarbon (Sorin Biomedica Cardio S.p.A., Saluggia, Italy) prosthesis. A follow-up was 100% complete and extended to 65 months (total 408 patient-years, average 2.0+/-1.4 years). Mean age at the operation was 75.1+/-5.5 years and 96% were in NYHA clinical stage III or IV. There were 86 men and 118 women; 73 patients had an isolated aortic valve disease, 131 had a concomitant cardiosurgical procedure (coronary artery bypass grafting in 106 patients). The operative mortality (30-day mortality) rate was 11.8% (24/204). There were 24 late deaths (5.9+/-1.2% patient-year). The actuarial probability of survival was 68+/-5% at 5 years. Four patients died of valve-related causes (one thromboembolic complication, two endocarditis, one anticoagulant-related hemorrhage). Actuarial rate of freedom from valve-related death was 95+/-3% at 5 years. Valve-related morbidity included seven thromboembolic episodes (1.7% patient-year), four anticoagulant-related complications (0.9% patient-year), three endocarditis (0.7% patient-year) and one reoperation (0.2% patient-year). After 5 years freedom from thromboembolic events was 83+/-7%, from anticoagulant-related hemorrhage 96+/-2%, from endocarditis 97+/-2%, and from reoperation 99+/-1%. Echocardiographic study performed in 30 patients showed a paraprosthetic leak in four patients, a central leak in two, and cusp thickening in another three. The clinical data showed that the Pericarbon prosthesis has valve-related morbidity. The echocardiographic results suggest that the prosthesis can undergo a pathologic process during the first 5 years after implantation. This makes it necessary to continue the follow-up and include the larger number of patients in the echocardiographic investigation.

Influence of left ventricular function on survival after coronary artery bypass grafting.

BACKGROUND: Preoperative left ventricular function is a most important predictor for survival in patients with ischemic heart disease. To elucidate the optimal timing of recommended coronary artery bypass grafting, we investigated the influence of different aspects of preoperative left ventricular function on relative survival. METHODS: To calculate the relative survival and estimate the disease-specific survival, we compared 6,514 patients who survived the first month after primary coronary artery bypass grafting with the general Swedish population stratified by age, sex, and 5-year calendar period. In particular we studied the relation between relative survival and different aspects of left ventricular performance, namely left ventricular function at rest, New York Heart Association functional class, and number of previous myocardial infarctions. RESULTS: The three variables (left ventricular function at rest, New York Heart Association functional class, and number of previous myocardial infarctions) as well as age and follow-up year gave independent information concerning relative survival. The results from this multivariate analysis were used to define a risk score for each patient. Patients were categorized into different risk groups. Patients in the low-risk group (30% of the total) showed a survival better than that of the population at large for 9 years after operation. The medium-risk group had no or low excess mortality for about 7 years, and the high-risk group (25%) showed increased excess mortality immediately after operation. CONCLUSIONS: If primary coronary artery bypass grafting is performed before the left ventricular function and physical performance deteriorate, survival is excellent.

Sternal wound complications--incidence, microbiology and risk factors.

OBJECTIVE: Sternal wound complications, i.e. instability and/or infection (mediastinitis), are important causes of morbidity in patients undergoing cardiac surgery via median sternotomy. Coagulase negative staphylococci, a normal inhabitant of the skin, have evolved as a cause of sternal wound infections. Since these opportunistic pathogens often are multiresistant, they can cause therapeutic problems. METHODS: From 1980 through 1995 open heart surgery, was performed on 13,285 adult patients. Reoperation necessitated by sternal wound complications occurerd in 203 patients (1.5%). The incidence was 1.7% (168/9987) after coronary artery bypass grafting (CABG group) and 0.7% (35/3413) after heart valve surgery with or without concomitant CABG (HVR group). RESULTS: Factors independently related to sternal complications in the CABG group (variable odds ratio [95% C.I.]): year of surgery, 1.9 [1.3-2.8] in 1990-1992, 2.0 [1.4-2.9] in 1993-1995; female sex, 0.4 [0.2-0.6]; diabetic disease, 1.8 [1.2-2.5]; bilateral ITA procedure, 3.3 [1.1-7.7]; and postoperative dialysis, 3.1 [1.4-6.9]. In the HVR group they were: use of ITA graft, 3.7 [1.7-7.7]; early re-exploration because of bleeding 3.0 [1.1-8.2]; and postoperative dialysis 3.1, [1.4-9.3]. Multivariate models were used to compute the risk for sternal complications in each patient. However, the prognostic models based on these risk scores provided low sensitivity and low predictive value. Patients with sternal wound complications showed no increased early mortality but worse long-term survival even after adjustment for other factors (relative hazard in CABG group 1.9 [1.2-2.8]; in HVR group 2.1 [1.1-4.3]. CONCLUSIONS: The use of ITA grafts seems to be one of the most important factors related to sternal wound complications. However, patients at truly increased risk for this complication could not be identified on the basis of the risk factors considered in this study.

The ventilation-perfusion relation and gas exchange in mitral valve disease and coronary artery disease. Implications for anesthesia, extracorporeal circulation, and cardiac surgery.

BACKGROUND: Patients with mitral valve disease (MVD) are at greater risk for respiratory complications after cardiac surgery compared with patients with coronary artery disease (CAD). The authors hypothesized that ventilation-perfusion (VA/Q) inequality is more pronounced in patients with MVD before and after induction of anesthesia and during and after surgery when extracorporeal circulation (ECC) is used. METHODS: In patients with MVD (n = 12) or with CAD (n = 12), VA/Q distribution was determined using the multiple inert gas elimination technique. Intrapulmonary shunt (Qs/Qr) defined as regions with VA/Q < 0.005 [% of total perfusion (Qr)], perfusion of "low" VA/Q areas (0.005 < or = VA/Q < 0.1, [% of Qr]), ventilation of "high" VA/Q regions (10 < or = VA/Q < or = 100 [% of total ventilation VE]), and dead space (VA/Q > 100 [% of VE]) were calculated from the retention/excretion data of the inert gases. Recordings were obtained while patients spontaneously breathed air in the awake state, during mechanical ventilation after induction of anesthesia, after separation of patients from ECC, and 4 h after operation. RESULTS: Qs/Qr was low in the awake state (MVD group, 3% +/- 3%; CAD group, 3% +/- 4%) and increased after induction of anesthesia to 10% +/- 8% (MVD group, P < 0.05) and 11% +/- 7% (CAD group, P < 0.01). Qs/Qr increased further after separation from ECC (MVD group, 24% +/- 9%, P < 0.01; CAD group, 23% +/- 7%, P < 0.01). Similarly, alveolar-arterial oxygen tension difference (PA-aO2) increased from 168 +/- 54 mmHg (anesthetized state) to 427 +/- 138 mmHg after ECC (MVD group, P < 0.01) and from 153 +/- 65 mmHg to 377 +/- 101 mmHg (CAD group, P < 0.01). In both groups, PA-aO2 was correlated with Qs/Qr. Four hours after operation, Qs/Qr had decreased significantly to 8% +/- 6% (CAD group) and 10% +/- 6% (MVD group). PA-aO2 and Qs/Qr showed no significant differences between the CAD and MVD groups. CONCLUSIONS: Qs/Qr is the main pathophysiologic mechanism of gas exchange impairment during cardiac surgery for MVD or CAD. Impairment of pulmonary gas exchange secondary to general anesthesia, cardiac surgery, and ECC are comparable for patients undergoing myocardial revascularization or mitral valve surgery.

Effects of heparin coating of cardiopulmonary bypass circuits on in vitro oxygen free radical production during coronary bypass surgery.

During cardiopulmonary bypass (CPB) oxygen free radicals (OFR) are formed, which can mediate reactions damaging tissue components. Blood contact with artificial surfaces during CPB leads to an activation of leukocytes, which are one of the sources of the OFR. Heparin coating of the CPB circuit reduces granulocyte activation. In the present study, the heparin-coated circuits with noncoated cardiotomy reservoirs (Group HC) were compared with noncoated, otherwise similar CPB sets (Group C). In each group, 8 patients were operated on for coronary revascularization. The release of granulocyte granule proteins myeloperoxidase (MPO) and lactoferrin (LF) was evaluated. Production of OFR in the whole blood and in the granulocyte suspension were measured by chemiluminescence (CL). In both groups the whole blood CL declined during CPB. The whole blood CL induced by serum-opsonized zymosan, when enhanced by luminol, was significantly lower in Group HC at 45 min after CPB start (68 +/- 6% of initial values in Group HC vs. 87 +/- 6% in Group C, mean +/- SEM) and 30 min after protaminization (54 +/- 6% of initial values in Group HC vs. 72 +/- 6% in Group C, mean +/- SEM), and CL was significantly higher in Group HC at CPB end (83 +/- 5% of initial values in Group HC vs. 67 +/- 5% in Group C, mean +/- SEM) when enhanced by lucigenin. CL of isolated granulocytes showed no significant differences between the groups. Release of MPO at CPB end and of LF 45 min after start of CPB and at CPB end were significantly lower in the heparin-coated CPB circuits.

Survival after coronary artery bypass grafting. Experience from 4661 patients.

The duration of the reduction of mortality after coronary artery bypass grafting (CABG) is an important issue and this study was undertaken to evaluate time in relation to excess mortality among CABG patients compared with the general population. Survival was analysed in 4661 patients who had undergone their first isolated CABG. Observed survival was related to that expected among subjects from the general Swedish population stratified by age, sex and 5-year calendar period, to calculate relative survival and estimate disease-specific survival. Relative survival (including all deaths) was 94.6% at 5 years, 82.5% at 10 years, and 59.9% at 15 years. A multivariate model based on relative survival rates adjusted for age, year of surgery, severity of coronary disease, left ventricular function, and smoking habits was used. Compared with the first year of follow-up, the relative hazard (a measure of the risk of death) was at a minimum 2 years after surgery, but was dramatically increased after about 8 years. Relative survival was worsened by smoking at the time of operation and by moderate or severe left ventricular dysfunction pre-operatively. The survival rate was higher among patients operated on after 1985 than among those operated on earlier.

Mitral valve prosthetic implantation with preservation of native mitral valve apparatus.

To avoid postoperative morbidity and mortality often associated with left ventricular dysfunction after mitral valve replacement (MVR) for chronic mitral insufficiency, reconstruction or preservation of the native mitral valve apparatus may be attempted during mitral prosthetic implantation (MPI). The effects of mitral surgery on heart function, studied with echocardiography and radionuclide angiography, were compared in seven patients with MPI (study group) and five with MVR (control group) who underwent complete preoperative, early postoperative and 3-6 months follow-up examinations. Preoperatively there was significant intergroup difference only in right ventricular ejection fraction measured at radionuclide angiography, which was lower in the MPI group (p < 0.05). At follow-up the MPI group had improved as regards this fraction (p < 0.005) and stroke volume index (p < 0.05). The number of patients with improved NYHA class at follow-up was significantly greater in the MPI group. Our preliminary experience with preservation of the native mitral valve apparatus thus suggests that the method offers haemodynamic advantages for postoperative right ventricular function.

Heparin-coated circuits reduce activation of granulocytes during cardiopulmonary bypass. A clinical study.

Activated granulocytes release highly active enzymes such as myeloperoxidase and lactoferrin, which can be involved in tissue destruction mediated by oxygen free radicals. Cardiopulmonary bypass has been reported to activate granulocytes. Bypass circuits coated with heparin have been shown to reduce release of granulocyte factors in experimental studies. In the present study, heparin-coated circuits were compared with noncoated circuits. In seven patients undergoing coronary bypass, heparin-coated circuits were used (group HC), and seven served as control patients (group C). In group HC the heparin dose was reduced to 75% (225 IU/kg). Group C had the standard dose of 300 IU/kg. No preoperative differences in myeloperoxidase and lactoferrin were observed between the groups. At the end of bypass in both groups, there was a significant increase of these enzymes (p less than 0.001) followed by a later decrease. In group HC, however, the release of myeloperoxidase was significantly lower than in group C (215 +/- 24 versus 573 +/- 133 micrograms/L, mean +/- standard error of the mean). The release of lactoferrin was significantly lower in group HC than in group C both at the end of cardiopulmonary bypass (659 +/- 79 versus 1448 +/- 121 micrograms/L) and 3 hours after bypass (224 +/- 37 versus 536 +/- 82 micrograms/L). Granulocytes as well as total number of leukocytes continued to increase until 1 hour after bypass (p less than 0.001) and then manifested a slow decrease. It was concluded that the use of heparin-coated circuits reduced the release of granulocyte factors because of lower activation of leukocytes.

Biochemical and functional effects of creatine phosphate in cardioplegic solution during aortic valve surgery--a clinical study.

During myocardial ischemia there is a drop in high-energy phosphates in the myocardium. Cold potassium cardioplegia decreases but does not altogether prevent this reduction. Supplementation of cardioplegic solutions with the high-energy compound creatine phosphate (10 mmol/L) compared to plain cardioplegic solutions was investigated in this study. Thirty patients scheduled for aortic valve replacement were included. The patients were randomized to group I (creatine phosphate) or group II (control). Postoperative hemodynamic evaluation revealed no significant differences between the groups. However, group I exhibited a tendency toward a better stroke-work index (135 +/- 18% vs. 102 +/- 5% recovery 15 minutes after bypass and 145 +/- 16% vs. 119 +/- 11% recovery 105 min after bypass). There were fewer patients in group I (5/15) needing inotropic support compared to group II (9/14). The myocardial content of ATP and creatine phosphate showed no significant differences during ischemia and reperfusion. It is concluded that the myocardial protection during ischemia was sufficient to prevent significant reductions of myocardial ATP and creatine phosphate irrespective of supplementation with CP.

Heparin-coated cardiopulmonary bypass circuits and 25% reduction of heparin dose in coronary artery surgery--a clinical study.

Cardiopulmonary bypass with systemic heparinization causes trauma to blood cells and coagulation defects. Artificial surfaces could be coated by end-linkage binding of heparin (Carmeda Bioactive Surface, CBAS). Use of such surfaces during cardiopulmonary bypass in animals resulted in less postoperative blood loss and better preservation of blood cells. In this study heparin-coated circuits were employed during coronary artery grafting in 7 patients (Group HC). Concomitantly, the heparin dose was reduced by 25% and an activated clotting time (ACT) of 300 sec was accepted. Additional 7 patients were operated with standard circuits (Group C), requiring ACT above 400 sec with normal doses of heparin. There were no thromboembolic complications in Group HC. The postoperative bleeding was generally low and without significant intergroup differences. Coagulation parameters displayed significantly lower ACT and anti-Factor Xa during bypass in Group HC. A tendency towards less blood cell trauma was observed with heparin-coated circuits. The protamine dose could be reduced by 50%, which significantly reduced the protamine/heparin quotient. This study indicates that routine cardiopulmonary bypass could be performed safely with heparin-coated circuits and reduced intravenous doses of heparin and protamine. It is suggested that the use of heparin-coated circuits may lead to less blood cell trauma.

Decreased blood loss after cardiopulmonary bypass using heparin-coated circuit and 50% reduction of heparin dose.

In a randomized, double-blind study of patients undergoing elective coronary artery grafting, the effect of heparin-coated circuit combined with 50% reduction of systemic heparin bolus was investigated. Ten patients comprised group HC (heparin-coated) and ten group C (controls). The mean total doses of heparin were 172 IU/kg in group HC and 416 IU/kg in group C and the respective protamine doses were 0.96 and 3.96 mg/kg (both p < 0.001). Activated clotting times during cardiopulmonary bypass were significantly shorter in group HC, and both intra- and postoperative bleeding was significantly less than in group C (7.7 vs. 11.7 ml/kg, p = 0.036, and 6.9 vs. 9.7 ml/kg, p = 0.004). Hemoglobin loss via the drains was 22.5 g in group HC and 43.7 g in group C (p < 0.005). Hemolysis at the end of bypass was significantly greater in group C. Apart from one perioperative myocardial infarction in group HC the postoperative course was uneventful. Use of a heparin-coated circuit is concluded to permit complication-free reduction of heparin and protamine doses and to decrease both intra- and postoperative bleeding, which may favorably influence the outcome of coronary artery grafting.

CT and MR evaluation of pericardial and retrosternal adhesions after cardiac surgery.

The visibility of the pericardium as well as of the space between the dorsal aspect of the sternal surface and the pericardial surface after cardiac surgery was determined by CT and/or MR with electrocardiographic (ECG)-gated spin-echo (SE) and gradient-echo sequences. Seventeen patients who had undergone cardiac operations and who were admitted for cardiac reoperation were investigated with CT and/or MR prior to sternal reentry. Five patients were investigated with CT alone, ten with both CT and MR, and two with MR only. At reoperation, retrosternal adhesions were classified as present or absent, and intrapericardial adhesions were classified as absent, minimal, moderate, or severe. A similar classification was applied to the CT and MR findings. In 14 of 15 patients, the CT findings were in agreement with those found at operation regarding postoperative retrosternal extrapericardial adhesions in the cranial retrosternal space and in 12 of 15 in the caudal retrosternal space. Computed tomography could not detect intrapericardial adhesions. Magnetic resonance was sensitive to metal artifacts from sternal sutures in both sequences and could therefore not be used to detect postoperative retrosternal extrapericardial adhesions. On the other hand, MR with ECG-gated SE sequences confirmed intrapericardial adhesions in 44 of 57 locations.

Risk factors for operative mortality and morbidity in patients undergoing coronary artery bypass surgery for stable angina pectoris.

Risk factors for a poor early outcome of surgery for stable angina pectoris were evaluated in 2659 consecutive patients from a defined population. The total operative mortality (death within 30 days after surgery) was 2.6% and the frequency of myocardial injury (increase in S-ASAT to greater than 2.0 mu kat l-1 and in S-CKMB to greater than 1.5 mu kat l-1 within 48 h postoperatively or death in the operating room) 14%. Mortality was related to New York Heart Association (NYHA) classification (P less than 0.001), age (less than or greater than 70 years, P = 0.001), duration of symptoms (less than or greater than 8 years, P = 0.001), aortic cross-clamp (ACC) time (P less than 0.001), and cardiopulmonary bypass (CBP) time (P less than 0.001). A multivariate analysis showed that the combination of NYHA class, ACC time and age best predicted operative mortality. Myocardial injury was related to NYHA functional class (P less than 0.001), duration of symptoms (P less than 0.001), regrafting procedure (P less than 0.001), cardiac related dyspnoea (P = 0.015), ACC time (P = 0.001), CPB time (P = 0.001), relative volume of cardioplegic solution (P less than 0.001), and thromboendarterectomy procedure (P = 0.004). The set of variables that best predicted myocardial injury consisted of ACC time, relative volume cardioplegic solution, NYHA class, regrafting procedure and duration of symptoms. However, these risk factors indicated only moderately high risks, and high-risk patients could not be selected with sufficient accuracy.

Early results of mitral valve replacement.

Early results of mitral valve replacement were reviewed in 336 unselected patients, 261 without and 75 with concomitant coronary artery bypass grafting (MVR and MVR + CABG groups). Early (less than 30 days) mortality was 7% in the MVR and 16% in the MVR + CABG group, with cardiac failure as the dominant cause. In multivariate analysis, the variables most strongly related to early mortality were congestive heart failure, diabetes and previous cardiac surgery in the MVR group and congestive heart failure in MVR + CABG. In the cases with fatal outcome the incidence of peroperative technical complications was 32% at MVR and 17% at MVR + CABG. The incidence of myocardial injury was 21% and 35% in the respective groups, and the early mortality in these cases was 19% vs 23%. Half of all fatal cases showed signs of peroperative myocardial injury. Multivariate analysis showed factors independently related to myocardial injury to be year of surgery and aortic cross-clamp time in MVR and previous cardiac surgery in MVR + CABG. Operation before cardiac reserves are reduced, optimal peroperative myocardial preservation and avoidance of technical errors should improve results of MVR.

Early results of aortic valve replacement with or without concomitant coronary artery bypass grafting.

Early results of aortic valve replacement were reviewed in 962 unselected patients, 659 without concomitant coronary bypass surgery (AVR group) and 303 with combined valve replacement and coronary artery bypass grafting (AVR + CABG). The early (less than 30-day) mortality was 4.6% in the AVR, and 5.9% in the AVR + CABG group. Multivariate analysis showed coronary artery stenoses and NYHA functional class to be independent predictors of early mortality in the AVR group, and the number of distal anastomoses as the strongest predictor in AVR + CABG. The incidence of peroperative technical complications in the cases with fatal outcome was 27% in the AVR and 6% in the AVR + CABG group. The incidence of myocardial injury (new Q wave or evidence of increased enzyme leakage) was 11% in AVR and 21% in AVR + CABG. Independent predictors of postoperative myocardial injury were aortic cross-clamp time, year of surgery, coronary artery stenoses and NYHA class in AVR and aortic cross-clamp time and year of surgery in AVR + CABG. The study suggests that coronary artery disease increases risk in aortic valve replacement with or without CABG. Replacement should be undertaken before endstage of the disease (NYHA IV), with CABG if significant coronary disease is present, and in multivessel disease the number of distal anastomoses should be restricted in order to shorten aortic cross-clamp time.